76738-62-0RMOGWMIKYWRTKW-DUXBJXIBNA-NRMOGWMIKYWRTKW-KGLIPLIRSA-N
Paclobutrazol1H-1,2,4-Triazole-1-ethanol, β-[(4-chlorophenyl)methyl]-α-(1,1-dimethylethyl)-, (αR,βR)-rel-
(2-RS,3RS)-1-(4-Chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pentan-3-ol
1H-1,2,4-Triazole-1-ethanol, β-[(4-chlorophenyl)methyl]-α-(1,1-dimethylethyl)-, (R*,R*)-
1H-1,2,4-Triazole-1-ethanol, β-[(4-chlorophenyl)methyl]-α-(1,1-dimethylethyl)-, (R*,R*)-(.+-.)-
Bounty Flowable
Clipper
Duo Xiao Zuo
Friazole
Multi-effect triazole
Smarect
Trimmit
DTXSID20242421836-75-5XITQUSLLOSKDTB-UHFFFAOYSA-NXITQUSLLOSKDTB-UHFFFAOYSA-N
NitrofenBenzene, 2,4-dichloro-1-(4-nitrophenoxy)-
2,4-Dichloro-1-(4-nitrophenoxy)benzene
2',4'-Dichloro-4-nitrodiphenyl ether
2,4-Dichloro-4'-nitrodiphenyl ether
2,4-Dichlorophenyl 4-nitrophenyl ether
2,4-Dichlorophenyl p-nitrophenyl ether
2,4-Dichlorophenyl-4'-nitrophenylether
4-(2,4-Dichlorophenoxy)nitrobenzene
4'-Nitro-2,4-dichlorodiphenyl ether
4-Nitro-2',4'-dichlorophenyl ether
Ether, 2,4-dichlorophenyl p-nitrophenyl
Mezotox
Niclofen
Nitrochlor
Nitrofen [benzene, 2,4-dichloro-1-(4-nitrophenoxy)-]
nitrofene
Preparation 125
Trizilin
Trizilin 25
DTXSID702097051-52-5KNAHARQHSZJURB-UHFFFAOYSA-NKNAHARQHSZJURB-UHFFFAOYSA-N
6-Propyl-2-thiouracil6-Propyl-2 thiouracil (PTU)
4(1H)-Pyrimidinone, 2,3-dihydro-6-propyl-2-thioxo-
2,3-Dihydro-6-propyl-2-thioxo-4(1H)-pyrimidinone
2-Mercapto-4-hydroxy-6-n-propylpyrimidine
2-Mercapto-4-hydroxy-6-propylpyrimidine
2-Mercapto-6-propylpyrimidin-4-ol
2-Thio-4-oxo-6-propyl-1,3-pyrimidine
2-Thio-6-propyl-1,3-pyrimidin-4-one
6-n-Propyl-2-thiouracil
6-n-Propylthiouracil
6-Propyl-2-thio-2,4(1H,3H)pyrimidinedione
6-Propylthiouracil
NSC 6498
NSC 70461
Procasil
Propacil
propiltiouracilo
Propycil
Propyl-Thiorist
Propylthiorit
propylthiouracil
Propylthiouracile
Propyl-Thyracil
Prothiucil
Prothiurone
Prothycil
Prothyran
Protiural
Thiuragyl
Thyreostat II
URACIL, 4-PROPYL-2-THIO-
Uracil, 6-propyl-2-thio-
DTXSID5021209UBERON:0000970eyePCO:0000001population of organismsVT:0002090vision traitPCO:0000008population growth rate7functional change2decreasedDisulphiram2019-05-22T05:17:392019-05-22T05:17:39Diethylaminobenzaldehyde2019-05-22T05:17:552019-05-22T05:17:55Citral2019-05-22T05:18:072019-05-22T05:18:07Paclobutrazol2019-05-22T05:18:202019-05-22T05:18:20nitrofen2019-05-22T05:18:442019-05-22T05:18:444-biphenyl carboxylic acid2019-05-22T05:18:552019-05-22T05:18:55Bisdiamine2019-05-22T05:19:082019-05-22T05:19:08SB-2106612019-05-22T05:19:222019-05-22T05:19:22Propylthiouracil2016-11-29T18:42:222016-11-29T18:42:22WCS_7955zebrafishWCS_8022rainbow trout10095mice10116ratWikiUser_28VertebratesWikiUser_22all speciesWikiUser_6fishRetinaldehyde dehydrogenase inhibitionRetinaldehyde dehydrogenaseMolecular2019-05-22T05:03:552019-05-22T05:03:55Altered, Photoreceptor patterningAltered, Photoreceptor patterningCellular<p dir="ltr"><strong>Photoreceptors in the retina of vertebrates and invertebrates are the cells that are responsible for phototransduction. The main groups of photoreceptor cells are rods, active at very low light levels, and cones, active at higher light levels and responsible for color vision. Photoreceptor subtypes are characterized by different opsins (light-sensitive proteins) that respond to light with different wavelengths.</strong></p>
<p dir="ltr"><strong>The opsin characterizing rods is rhodopsin. Cones are further divided in several subtypes. The opsins characterizing these subtypes are generally grouped in S-opsins (short wavelength-sensitive), M-opsins (medium wavelength-sensitive) and L-opsins (long wavelength-sensitive). The occurrence of different opsins is species-specific (see Taxonomic applicability). </strong></p>
<p dir="ltr"><strong>The distribution of photoreceptor subtypes within the retina is also referred to as photoreceptor patterning and has a quantitative component (typical ratios of photoreceptor subtypes) as well as a spatial component (organization of photoreceptor subtypes). Depending on the species, the spatial organization is stochastic/regionalized (human, fruit fly), regionalized (mouse), or ordered (zebrafish).</strong></p>
<p dir="ltr"><strong>During early development, photoreceptor subtypes differentiate from retinal progenitor cells. In a later stage of embryo or juvenile development, already differentiated cone photoreceptors can also switch opsin expression to a different opsin type. In general, this opsin switch is characterized by a switch in opsin expression from short to longer wavelength-sensitive opsins. An opsin switch is part of normal eye development and has been documented mostly in fish species (Shand et al., 2002; Cheng et al., 2006; Cheng and Flamarique, 2007; Matsumoto and Ishibashi, 2016; Mackin et al., 2019), and also in rodents (Lukats et al., 2005). </strong></p>
<p dir="ltr"><strong>Under some circumstances, photoreceptor patterning and opsin switching can be altered. This can manifest itself as altered numbers of photoreceptor subtypes leading to an altered ratio of photoreceptor subtypes and/or altered spatial organization (Raymond et al., 2014).</strong></p>
<p><br />
</p>
<p dir="ltr"><strong>In general, photoreceptor cell types are quantified and/or localized based on their opsin expression. The target for measurement therefore are the opsins. They can be measured either on the mRNA or on the protein level.</strong></p>
<p dir="ltr"><strong>Altered opsin expression patterns indicative of altered ratios of photoreceptor subtypes are often detected by relative quantification of mRNA coding for the specific opsins expressed in the photoreceptor subtypes using qPCR (quantitative polymerase chain reaction) (Allison et al., 2006; Mackin et al., 2019). This is a straightforward technique that many laboratories have available.</strong></p>
<p dir="ltr"><strong>Several methods can be used to obtain information on spatial patterning and to count photoreceptor types. </strong></p>
<ul>
<li dir="ltr">
<p dir="ltr"><strong>Immunohistochemistry allows for labelling specific opsins (protein level) with antibodies, mostly through the use of primary antibodies specific to the target and secondary antibodies that bind to the primary antibodies and are conjugated to e.g., a fluorescent label or alkaline phosphatase that produces a measurable product (Allison et al., 2006; DuVal et al., 2014; Houbrechts et al., 2016; DuVal and Allison, 2018). This is typically performed on retinal wholemounts or cryosections. </strong></p>
</li>
<li dir="ltr">
<p dir="ltr"><strong>In situ hybridization is used to label opsin mRNA using complementary oligonucleotide probes on retinal sections (Allison et al., 2006; Gan and Flamarique, 2010; Glaschke et al., 2010; DuVal et al., 2014; Karagic et al., 2018; Mackin et al., 2019).</strong></p>
</li>
<li dir="ltr">
<p dir="ltr"><strong>Zebrafish transgenic lines expressing fluorescent reporters in specific photoreceptor types (again associated with opsin expression) have also been successfully used to analyse photoreceptor counts, spatial patterning and opsin switches (Raymond et al., 2014; Mackin et al., 2019). Examples include lines reporting rhodopsin, blue cone or UV cone expression (Raymond et al., 2014).</strong></p>
</li>
</ul>
<p dir="ltr"><strong>Based on available evidence, it seems plausible that this key event is applicable across all life stages and for a wide variety of taxa including vertebrates and invertebrates.</strong></p>
<ol>
<li dir="ltr">
<p dir="ltr"><strong>Taxonomic applicability</strong></p>
</li>
</ol>
<p dir="ltr"><strong>Rod and cone pigments all diverged from a common ancestor through a series of duplication events (Nathans et al., 1986). These duplication events gave rise to important taxonomic differences in opsin genes. As an example, humans have three cone photoreceptor types expressing long (L, red), medium (M, green), or short (S, blue) wavelength‐specific opsins (Nathans et al., 1986), while the zebrafish genome has two red (LWS-1 and LWS-2), four green (RH2-1, RH2-2, RH2-3, and RH2-4), and single blue (SWS2) and ultraviolet (SWS1) opsin genes (Chinen et al., 2003). Suzuki et al. (2013) further discuss that some species have pure cone types that express a single opsin, while others have mixed cone types expressing different opsins simultaneously. The authors suggested that expression of thrbeta2 in progenitor cells results in pure L-opsin cones in zebrafish. This is opposed to expression of thrbeta2 in later in postmitotic cells resulting in mixed cones in mice.</strong></p>
<p dir="ltr"><strong>The importance of normal ratios of photoreceptor types and the concept of photoreceptor patterning however seems to be applicable to a wide range of species, including vertebrates and invertebrates. Retinal patterning of different taxa can be stochastic/regionalized (human, fruit fly), regionalized (mouse), or ordered (zebrafish) and has evolved to suit different environments and behaviors (Raymond et al., 2014; Viets et al., 2016). Since normal patterning differs among taxa, changes in patterning should be considered within species.</strong></p>
<p dir="ltr"><strong>During early development, photoreceptor subtypes differentiate from retinal progenitor cells. In a later stage of embryo or juvenile development, already differentiated cone photoreceptors can also switch opsin expression to a different opsin type. Such opsin switch is part of normal eye development and has been documented mostly in fish (Shand et al., 2002; Cheng et al., 2006; Cheng and Flamarique, 2007; Matsumoto and Ishibashi, 2016), and also in rodents (Lukats et al., 2005) and humans (Cornish et al., 2004). This opsin switch is characterized by a switch in opsin expression from short to longer wavelength-sensitive opsins. For example, in salmonids, single cones express ultraviolet (SWS-1) opsin during embryonic development and switch to blue (SWS-2) opsin as the fish grow (Gan and Flamarique, 2010). In zebrafish a switch occurs from LWS-2 to the longer wavelength LWS-1 opsin (Tsujimura et al., 2010; Mitchell et al., 2015; Mackin et al., 2019). Mitchell et al. (2015) and Mackin et al. (2019) even confirmed opsin switching in real time using developing transgenic zebrafish. In rodents and humans, the opsin switch involves a switch from S to M opsins.</strong></p>
<p dir="ltr"><strong>Teleost fish and salamanders are capable of regenerating the retina following injury, while mammals do not have this innate capacity to regenerate the retina (Mader and Cameron, 2004; Lamba et al., 2008; Van Gelder and Kaur, 2015). Studies have shown however that opsin expression in terminally differentiated mammalian cones also remains subject to alterations (Glaschke et al., 2011). Therefore, in addition to alterations during development, alterations of photoreceptor patterning in the adult retina are also expected to be relevant across taxa.</strong></p>
<ol start="2">
<li dir="ltr">
<p dir="ltr"><strong>Life-stage applicability</strong></p>
</li>
</ol>
<p dir="ltr"><strong>Normal photoreceptor patterning is established during development and this process can be altered by various circumstances (Mackin et al., 2019). Therefore, this key event is applicable to early life stages in which the retina is under development.</strong></p>
<p dir="ltr"><strong>Juvenile zebrafish show some plasticity in opsin expression (Mackin et al., 2019). This type of phenotypic plasticity appears common among fish as a result of changes in habitats. </strong></p>
<p dir="ltr"><strong>Since teleosts and salamanders can regenerate the retina after injury, the process of restoring photoreceptor patterning can also be affected in the adult life stage (Mader and Cameron, 2006). </strong></p>
<p dir="ltr"><strong>In adult mice and rats, the normal pattern of opsin expression and distribution can be reversibly altered, suggesting that opsin expression in terminally differentiated mammalian cones also remains subject to alterations (Glaschke et al., 2011). </strong></p>
<p dir="ltr"><strong>Taken together, there is good evidence that this key event is applicable across all life stages.</strong></p>
<ol start="3">
<li dir="ltr">
<p dir="ltr"><strong>Sex applicability</strong></p>
</li>
</ol>
<p dir="ltr"><strong>Zebrafish are undifferentiated gonochorists since both sexes initially develop an immature ovary (Maack and Segner, 2003). Immature ovary development progresses until approximately the onset of the third week. Later, in female fish immature ovaries continue to develop further, while male fish undergo transformation of ovaries into testes. Final transformation into testes varies among male individuals, however finishes usually around 6 weeks post fertilization. Establishment of photoreceptor patterning during early development is therefore expected to be independent of sex.</strong></p>
<p dir="ltr"><strong>A few studies have shown that sex hormones can regulate spectral sensitivity, and this is probably related to the importance of perceiving breeding coloration. In sexually mature male sticklebacks, androgen is a key factor in enhancing sensitivity to red light via regulation of opsin gene expression (Shao et al., 2014). This is in line with the need to detect the red breeding color of males during the breeding season. Lizards also regulate opsin expression seasonally, and this appears to be related to evaluation of the coloration of potential mates. Tseng et al. (2018) showed that testosterone regulates opsin expression in a sexually dimorphic lizard and that males and females show opposite shifts in opsin expression during the breeding season.</strong></p>
<p dir="ltr"><strong>In mammals, medium (green) and long (red) wavelength-sensitive opsin genes are located on the X chromosome, leading to sex-linked color vision deficiencies where male individuals are more susceptible (Jacobs, 2009). </strong></p>
<p dir="ltr"><strong>Studies have shown sexual dimorphism of photoreceptor patterning in Arthropoda such as the fruitfly and the small white butterfly (Arikawa et al., 2005; Hilbrant et al., 2014). The crustacean Euphilomedes carcharodonta exhibits radical sexual dimorphism of the lateral eyes. Females have only a tiny, simple lateral eye while males have elaborate ommatidial eyes. This coincides with differences in the expression of genes related to eye development and phototransduction (Sajuthi et al., 2015). </strong></p>
<p dir="ltr"><strong>Alterations in normal photoreceptor patterning can be expected to occur across sexes. Based on the general evidence of sexual dimorphism in terms of spectral sensitivity, sex specific alterations may occur in sexually mature organisms.</strong></p>
<p><br />
</p>
UBERON:0000966retinaModerateMaleNot SpecifiedFemaleModerateEmbryoModerateJuvenileModerateLarvaeHighAll life stagesHighModerateNot SpecifiedNot SpecifiedModerate<p dir="ltr"><strong>Allison, W.T., Dann, S.G., Veldhoen, K.M., Hawryshyn, C.W., 2006. Degeneration and regeneration of ultraviolet cone photoreceptors during development in rainbow trout. Journal of Comparative Neurology 499, 702-715.</strong></p>
<p dir="ltr"><strong>Arikawa, K., Wakakuwa, M., Qiu, X.D., Kurasawa, M., Stavenga, D.G., 2005. Sexual dimorphism of short-wavelength photoreceptors in the small white butterfly, Pieris rapae crucivora. Journal of Neuroscience 25, 5935-5942.</strong></p>
<p dir="ltr"><strong>Cheng, C.L., Flamarique, I.N., 2007. Chromatic organization of cone photoreceptors in the retina of rainbow trout: single cones irreversibly switch from UV (SWS1) to blue (SWS2) light sensitive opsin during natural development. Journal of Experimental Biology 210, 4123-4135.</strong></p>
<p dir="ltr"><strong>Cheng, C.L., Flamarique, I.N., Harosi, F.I., Rickers-Haunerland, J., Haunerland, N.H., 2006. Photoreceptor layer of salmonid fishes: Transformation and loss of single cones in juvenile fish. Journal of Comparative Neurology 495, 213-235.</strong></p>
<p dir="ltr"><strong>Chinen, A., Hamaoka, T., Yamada, Y., Kawamura, S., 2003. Gene duplication and spectral diversification of cone visual pigments of zebrafish. Genetics 163, 663-675.</strong></p>
<p dir="ltr"><strong>Cornish, E.E., Xiao, M., Yang, Z.T., Provis, J.M., Hendrickson, A.E., 2004. The role of opsin expression and apoptosis in determination of cone types in human retina. Experimental Eye Research 78, 1143-1154.</strong></p>
<p dir="ltr"><strong>DuVal, M.G., Allison, W.T., 2018. Photoreceptor Progenitors Depend Upon Coordination of gdf6a, thr beta, and tbx2b to Generate Precise Populations of Cone Photoreceptor Subtypes. Investigative Ophthalmology & Visual Science 59, 6089-6101.</strong></p>
<p dir="ltr"><strong>DuVal, M.G., Oel, A.P., Allison, W.T., 2014. gdf6a Is Required for Cone Photoreceptor Subtype Differentiation and for the Actions of tbx2b in Determining Rod Versus Cone Photoreceptor Fate. Plos One 9.</strong></p>
<p dir="ltr"><strong>Gan, K.J., Flamarique, I.N., 2010. Thyroid Hormone Accelerates Opsin Expression During Early Photoreceptor Differentiation and Induces Opsin Switching in Differentiated TR alpha-Expressing Cones of the Salmonid Retina. Developmental Dynamics 239, 2700-2713.</strong></p>
<p dir="ltr"><strong>Glaschke, A., Glosmann, M., Peichl, L., 2010. Developmental Changes of Cone Opsin Expression but Not Retinal Morphology in the Hypothyroid Pax8 Knockout Mouse. Investigative Ophthalmology & Visual Science 51, 1719-1727.</strong></p>
<p dir="ltr"><strong>Glaschke, A., Weiland, J., Del Turco, D., Steiner, M., Peichl, L., Glosmann, M., 2011. Thyroid Hormone Controls Cone Opsin Expression in the Retina of Adult Rodents. Journal of Neuroscience 31, 4844-4851.</strong></p>
<p dir="ltr"><strong>Hilbrant, M., Almudi, I., Leite, D.J., Kuncheria, L., Posnien, N., Nunes, M.D.S., McGregor, A.P., 2014. Sexual dimorphism and natural variation within and among species in the Drosophila retinal mosaic. Bmc Evolutionary Biology 14.</strong></p>
<p dir="ltr"><strong>Houbrechts, A.M., Vergauwen, L., Bagci, E., Van Houcke, J., Heijlen, M., Kulemeka, B., Hyde, D.R., Knapen, D., Darras, V.M., 2016. Deiodinase knockdown affects zebrafish eye development at the level of gene expression, morphology and function. Molecular and Cellular Endocrinology 424, 81-93.</strong></p>
<p dir="ltr"><strong>Jacobs, G.H., 2009. Evolution of colour vision in mammals. Philosophical Transactions of the Royal Society B-Biological Sciences 364, 2957-2967.</strong></p>
<p dir="ltr"><strong>Karagic, N., Harer, A., Meyer, A., Torres-Dowdall, J., 2018. Heterochronic opsin expression due to early light deprivation results in drastically shifted visual sensitivity in a cichlid fish: Possible role of thyroid hormone signaling. Journal of Experimental Zoology Part B-Molecular and Developmental Evolution 330, 202-214.</strong></p>
<p dir="ltr"><strong>Lamba, D., Karl, M., Rehl, T., 2008. Neural regeneration and cell replacement: A view from the eye. Cell Stem Cell 2, 538-549.</strong></p>
<p dir="ltr"><strong>Lukats, A., Szabo, A., Rohlich, P., Vigh, B., Szel, A., 2005. Photopigment coexpression in mammals: comparative and developmental aspects. Histology and Histopathology 20, 551-574.</strong></p>
<p dir="ltr"><strong>Maack, G., Segner, H., 2003. Morphological development of the gonads in zebrafish. Journal of Fish Biology 62, 895-906.</strong></p>
<p dir="ltr"><strong>Mackin, R.D., Frey, R.A., Gutierrez, C., Farre, A.A., Kawamura, S., Mitchell, D.M., Stenkamp, D.L., 2019. Endocrine regulation of multichromatic color vision. Proceedings of the National Academy of Sciences of the United States of America 116, 16882-16891.</strong></p>
<p dir="ltr"><strong>Mader, M., Cameron, D., 2006. Effects of induced systemic hypothyroidism upon the retina: Regulation of thyroid hormone receptor alpha and photoreceptor production. Molecular Vision 12, 915-930.</strong></p>
<p dir="ltr"><strong>Mader, M.M., Cameron, D.A., 2004. Photoreceptor differentiation during retinal development, growth, and regeneration in a metamorphic vertebrate. Journal of Neuroscience 24, 11463-11472.</strong></p>
<p dir="ltr"><strong>Matsumoto, T., Ishibashi, Y., 2016. Sequence analysis and expression patterns of opsin genes in the longtooth grouper Epinephelus bruneus. Fisheries Science 82, 17-27.</strong></p>
<p dir="ltr"><strong>Mitchell, D.M., Stevens, C.B., Frey, R.A., Hunter, S.S., Ashino, R., Kawamura, S., Stenkamp, D.L., 2015. Retinoic Acid Signaling Regulates Differential Expression of the Tandemly-Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish. Plos Genetics 11.</strong></p>
<p dir="ltr"><strong>Nathans, J., Thomas, D., Hogness, D.S., 1986. MOLECULAR-GENETICS OF HUMAN COLOR-VISION - THE GENES ENCODING BLUE, GREEN, AND RED PIGMENTS. Science 232, 193-202.</strong></p>
<p dir="ltr"><strong>Raymond, P.A., Colvin, S.M., Jabeen, Z., Nagashima, M., Barthel, L.K., Hadidjojo, J., Popova, L., Pejaver, V.R., Lubensky, D.K., 2014. Patterning the Cone Mosaic Array in Zebrafish Retina Requires Specification of Ultraviolet-Sensitive Cones. Plos One 9.</strong></p>
<p dir="ltr"><strong>Sajuthi, A., Carrillo-Zazueta, B., Hu, B., Wang, A., Brodnansky, L., Mayberry, J., Rivera, A.S., 2015. Sexually dimorphic gene expression in the lateral eyes of Euphilomedes carcharodonta (Ostracoda, Pancrustacea). Evodevo 6.</strong></p>
<p dir="ltr"><strong>Shand, J., Hart, N.S., Thomas, N., Partridge, J.C., 2002. Developmental changes in the cone visual pigments of black bream Acanthopagrus butcheri. Journal of Experimental Biology 205, 3661-3667.</strong></p>
<p dir="ltr"><strong>Shao, Y.T., Wang, F.Y., Fu, W.C., Yan, H.Y., Anraku, K., Chen, I.S., Borg, B., 2014. Androgens Increase Iws Opsin Expression and Red Sensitivity in Male Three-Spined Sticklebacks. Plos One 9.</strong></p>
<p dir="ltr"><strong>Tseng, W.H., Lin, J.W., Lou, C.H., Lee, K.H., Wu, L.S., Wang, T.Y., Wang, F.Y., Irschick, D.J., Lin, S.M., 2018. Opsin gene expression regulated by testosterone level in a sexually dimorphic lizard. Scientific Reports 8.</strong></p>
<p dir="ltr"><strong>Tsujimura, T., Hosoya, T., Kawamura, S., 2010. A Single Enhancer Regulating the Differential Expression of Duplicated Red-Sensitive Opsin Genes in Zebrafish. Plos Genetics 6.</strong></p>
<p dir="ltr"><strong>Van Gelder, R.N., Kaur, K., 2015. Vision Science: Can Rhodopsin Cure Blindness? Current Biology 25, R713-R715.</strong></p>
<p dir="ltr"><strong>Viets, K., Eldred, K.C., Johnston, R.J., 2016. Mechanisms of Photoreceptor Patterning in Vertebrates and Invertebrates. Trends in Genetics 32, 638-659.</strong></p>
<p><br />
</p>
2019-05-22T05:06:402021-06-16T06:56:20Decreased retinoic acid (RA) synthesisretinoic acidCellular2019-05-22T05:10:172019-05-22T05:10:17Decreased plasma RA levelplasma retionic acidTissue2019-05-22T05:11:022019-05-22T05:11:02Altered, Visual functionAltered, Visual functionOrgan<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">The decrease in visual function can have different aspects, such as loss of chromatic vision, changes in eye movements, differences in sensitivity to light, but also changes in the retinal pigment epithelium (RPE) that may be related to a decrease in visual function (Strauss, 2005). The visual system is highly variable from one species to another, and this variability is a key factor influencing animal behaviour (Corral-López et al., 2017).</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Decreases in these visual functions can have a strong impact on behaviour, leading to changes in individual response and abilities in the environment, including, for example, perception of food or avoidance of predators. Variation in the visual system can also influence learning tasks when visual stimuli are used (Corral-López et al., 2017).</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Studies have detected visual impairments in fish at different temperatures (Babkiewicz et al., 2020) after treatment with the endocrine disruptor propylthiouracil (Baumann et al 2016 ), after chronic dietary selenomethionine exposure (Raine et al 2016), exposure to PCBs (Zhang et al, 2015) or deiodinase knockdown (Houbrechts et al 2016, Vancamp et al 2018).</span></span></span></span></p>
<p><br />
</p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Measurements of visual function can be performed at the level of neuronal activity:</span></span></span></span></p>
<ul>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Electroretinography (Chrispell et al., 2015)</span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Analysis of neural activity in the optic tectum can be quantified as the ratio of phosphorylated extracellular signal–regulated kinase (ERK) to total ERK in the optic tectum using immunofluorescent antibodies (Randlett et al., 2015, Dehnert et al., 2019).</span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Babkiewicz et al. (2020) used an advanced technique to display an artificial prey on a miniature OLED screen and use functional calcium imaging with light sheet microscopy to visualize a neural response in the optic tectum.</span></span></li>
</ul>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Other measurements are performed at the level of the eyes:</span></span></span></span></p>
<ul>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Opto Kinetic response, OKR (similar protocol for Rat/mice (Segura et al., 2018), fish (Zou et al., 2010) and humans (Kang and Wildsoet, 2016)). The OKR is a visually-mediated assay in which an individual will respond to alternating black and white stripes by exhibiting eye saccades, eye movements without coordinated body movements, in the same direction as rotating stripes. An eye saccade relies on the ability to rapidly move the eye from focusing on one external target to the next in a repeated manner (Magnuson et al., 2020). Optokinetic tracking has a robust performance and does not require training the animal, allowing for the quick assessment (and at earlier ages) of visual features such as visual acuity (VA) and contrast sensitivity (CS)11–14. </span></span></li>
</ul>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Yet other studies use assessment of vision-related behaviours: </span></span></span></span></p>
<ul>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Opto Motor Reponses, OMR. OMR tracks the ability of fish to swim in the direction of a perceived motion when presented with a whole-field stimulus (Neuhauss, 2003), (Gould et al., 2017)).</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Light-dark transition or vision startle response: reaction to change in light intensity (light sensitivity) (Brastrom et al., 2019)</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Black-white preference test (Baumann et al., 2016)</span></span></span></li>
</ul>
<ul>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Diverse Mobility assay including Tracking, touch-evoked escape-response assays, Swirl assays, locomotion assay, swimming activity, phototactic swimming activity assay, induced locomotor response (LLR) (Baumann et al., 2016; Gao et al., 2015; Zhao et al., 2014, Dehnert et al., 2019).</span></span></span></li>
</ul>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong><span style="color:black">Taxonomic applicability</span></strong><span style="color:black">: Visual function decrease can be evaluated in </span><span style="color:black">a </span><span style="color:black">wide range of species including mammals, amphibians, fish and humans. Evaluation of these visual function modification</span><span style="color:black">s</span><span style="color:black"> change according to the species and its environment.</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong><span style="color:black">Life-stage applicability</span></strong><span style="color:black">: Vision plays a crucial role in the early life stages of most species, as timing of eye development and establishment of functional vision is essential for perception of food or avoidance of predators for example (Carvalho et al., 2002).</span> <span style="color:black">The first visual responses based on retinal functionality appear around 70 hpf in zebrafish (Schmitt and Dowling 1999). It is plausible to assume that alterations of the eye structure would result in altered visual function across all life stages, but such alterations are most likely to occur during the development of the normal eye structure, which occurs in the embryo-eleutheroembryo phase. Some studies have also shown a decrease in vision related to age (Brastrom et al., 2019; Martínez-Roda et al., 2016; Segura et al., 2018) including on visual acuity, visual fields, colour vision and dark adaptation, are well documented (Hennelly et al, 1998).</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong><span style="color:black">Sex applicability</span></strong><span style="color:black">: Sex does not seem relevant for most of the visual function decreases observed in different studies. Differences according to the sex of the individuals have however been reported concerning the basic visual capacities (e.g. color perception, contrast sensitivity, visual acuity, motion perception,...) but also concerning the frequency of certain diseases influencing these diminished visual functions, notably in humans (Vanston and Strother, 2017).</span></span></span></span></p>
<p><br />
</p>
UBERON:0000970eyeModerateUnspecificHighEmbryoModerateJuvenileHighLarvaeHigh<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">Baumann, L., Ros, A., Rehberger, K., Neuhauss, S. C. F., & Segner, H. (2016). Thyroid disruption in zebrafish (Danio rerio) larvae: Different molecular response patterns lead to impaired eye development and visual functions. Aquatic Toxicology, 172, 44–55. https://doi.org/10.1016/j.aquatox.2015.12.015</span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">Babkiewicz, E., Bazała, M., Urban, P., Maszczyk, P., Markowska, M., & Maciej Gliwicz, Z. (2020). The effects of temperature on the proxies of visual detection of Danio rerio larvae: observations from the optic tectum. Biology Open, 9(7). https://doi.org/10.1242/BIO.047779</span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">Brastrom, L.K., Scott, C.A., Dawson, D. V., Slusarski, D.C., 2019. A High-Throughput Assay for Congenital and Age-Related Eye Diseases in Zebrafish. Biomedicines 7, 28. https://doi.org/10.3390/biomedicines7020028</span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">Carvalho, P.S.M., Noltie, D.B., Tillitt, D.E., 2002. Ontogenetic improvement of visual function in the medaka Oryzias latipes based on an optomotor testing system for larval and adult fish. Anim. Behav. 64, 1–10. https://doi.org/10.1006/anbe.2002.3028</span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">Chrispell JD, Rebrik TI, Weiss ER. 2015. Electroretinogram Analysis of the Visual Response in Zebrafish Larvae. Jove-Journal of Visualized Experiments(97).</span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">Corral-López, A., Garate-Olaizola, M., Buechel, S.D., Kolm, N., Kotrschal, A., 2017. On the role of body size, brain size, and eye size in visual acuity. Behav. Ecol. Sociobiol. 71. https://doi.org/10.1007/s00265-017-2408-z</span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">Dehnert GK, Karasov WH, Wolman MA. 2019. 2,4-Dichlorophenoxyacetic acid containing herbicide impairs essential visually guided behaviors of larval fish. Aquatic Toxicology 209:1-12.</span></span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Gao, D., Wu, M., Wang, C., Wang, Y., Zuo, Z., 2015. Chronic exposure to low benzo[a]pyrene level causes neurodegenerative disease-like syndromes in zebrafish (Danio rerio). Aquat. Toxicol.</span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Gould, C. J., Wiegand, J. L., & Connaughton, V. P. (2017). Acute developmental exposure to 4-hydroxyandrostenedione has a long-term effect on visually-guided behaviors. Neurotoxicology and Teratology, 64, 45–49. https://doi.org/10.1016/j.ntt<a href="https://doi.org/10.1016/j.ntt.2017.10.003">.</a>2017.10.003</span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Hennelly, M. L., Barbur, J. L., Edgar, D. F., & Woodward, E. G. (1998). The effect of age on the light scattering characteristics of the eye. Ophthalmic and Physiological Optics, 18(2), 197–203. https://doi.org/10.1046/j.1475-1313.1998.00333.x</span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Houbrechts, A. M., Vergauwen, L., Bagci, E., Van houcke, J., Heijlen, M., Kulemeka, B., Hyde, D. R., Knapen, D., & Darras, V. M. (2016). Deiodinase knockdown affects zebrafish eye development at the level of gene expression, morphology and function. Molecular and Cellular Endocrinology, 424, 81–93. https://doi.org/10.1016/j.mce.2016.01.018</span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Kang, P., & Wildsoet, C. F. (2016). Acute and short-term changes in visual function with multifocal soft contact lens wear in young adults. Contact Lens and Anterior Eye, 39(2), 133–140. https://doi.org/10.1016/j.clae.2015.09.004</span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Magnuson, J., Bautista, N., Lucero, J., Lund, A., Xu, E. G., Schlenk, D., Burggren, W., & Roberts, A. P. (2020). Exposure to crude oil induces retinal apoptosis and impairs visual function in fish. Environmental Science & Technology. https://doi.org/10.1021/acs.est.9b07658</span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Martínez-Roda, J. A., Vilaseca, M., Ondategui, J. C., Aguirre, M., & Pujol, J. (2016). Effects of aging on optical quality and visual function. Clinical and Experimental Optometry, 99(6), 518–525. https://doi.org/10.1111/cxo.12369</span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Neuhauss, S. C. F. (2003). Behavioral genetic approaches to visual system development and function in zebrafish. Journal of Neurobiology, 54(1), 148–160. https://doi.org/10.1002/neu.10165</span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">Raine, J. C., Lallemand, L., Pettem, C. M., & Janz, D. M. (2016). Effects of Chronic Dietary Selenomethionine Exposure on the Visual System of Adult and F1 Generation Zebrafish (Danio rerio). Bulletin of Environmental Contamination and Toxicology, 97(3), 331–336. https://doi.org/10.1007/s00128-016-1849-9</span></span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Randlett O, Wee CL, Naumann EA, Nnaemeka O, Schoppik D, Fitzgerald JE, Portugues R, Lacoste AMB, Riegler C, Engert F et al. . 2015. Whole-brain activity mapping onto a zebrafish brain atlas. Nature Methods 12(11):1039-1046.</span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Schmitt, E. A., & Dowling, J. E. (1994). Early‐eye morphogenesis in the zebrafish, Brachydanio rerio. Journal of Comparative Neurology, 344(4), 532–542. https://doi.org/10.1002/cne.903440404</span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Segura, F., Arines, J., Sánchez-Cano, A., Perdices, L., Orduna-Hospital, E., Fuentes-Broto, L., & Pinilla, I. (2018). Development of optokinetic tracking software for objective evaluation of visual function in rodents. Scientific Reports, 8(1), 1–11. https://doi.org/10.1038/s41598-018-28394-x</span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Strauss, O. (2005). The retinal pigment epithelium in visual function. Physiological Reviews, 85(3), 845–881.https://doi.org/10.1152/physrev.00021.2004</span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">Vancamp, P., Bourgeois, N. M. A., Houbrechts, A. M., & Darras, V. M. (2019). Knockdown of the thyroid hormone transporter MCT8 in chicken retinal precursor cells hampers early retinal development and results in a shift towards more UV/blue cones at the expense of green/red cones. Experimental Eye Research,178(September 2018), 135–147. https://doi.org/10.1016/j.exer.2018.09.018</span></span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Zhang, X., Hong, Q., Yang, L., Zhang, M., Guo, X., Chi, X., & Tong, M. (2015). PCB1254 exposure contributes to the abnormalities of optomotor responses and influence of the photoreceptor cell development in zebrafish larvae. Ecotoxicology and Environmental Safety, 118, 133–138. https://doi.org/10.1016/j.ecoenv.2015.04.026</span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Zhao, J., Xu, T., & Yin, D. Q. (2014). Locomotor activity changes on zebrafish larvae with different 2,2’,4,4’-tetrabromodiphenyl ether (PBDE-47) embryonic exposure modes. Chemosphere, 94, 53–61. https://doi.org/10.1016/j.chemosphere.2013.09.010</span></span></p>
<p><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Zou, S. Q., Yin, W., Zhang, M. J., Hu, C. R., Huang, Y. bin, & Hu, B. (2010). Using the optokinetic response to study visual function of zebrafish. Journal of Visualized Experiments, 36, 5–8. https://doi.org/10.3791/1742</span></span></p>
2019-05-22T05:12:282022-07-08T07:30:59Decrease, Population growth rateDecrease, Population growth ratePopulation<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">A population can be defined as a group of interbreeding organisms, all of the same species, occupying a specific space during a specific time (Vandermeer and Goldberg 2003, Gotelli 2008). As the population is the biological level of organization that is often the focus of ecological risk</span> <span style="color:black">assessments, population growth rate (and hence population size over time) is important to consider within the context of applied conservation practices.</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">If N is the size of the population and t is time, then the population growth rate (dN/dt) is proportional to the instantaneous rate of increase, r, which measures the per capita rate of population increase over a short time interval. Therefore, r, is a difference between the instantaneous birth rate (number of births per individual per unit of time; b) and the instantaneous death rate (number of deaths per individual per unit of time; d) [Equation 1]. Because r is an instantaneous rate, its units can be changed via division. For example, as there are 24 hours in a day, an r of 24 individuals/(individual x day) is equal to an r of 1 individual/(individual/hour) (Caswell 2001, Vandermeer and Goldberg 2003, Gotelli 2008, Murray and Sandercock 2020). </span></span></span></span></p>
<p style="margin-left:144px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Equation 1: r = b - d</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">This key event refers to scenarios where r < 0 (instantaneous death rate exceeds instantaneous birth rate).</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Examining r in the context of population growth rate:</span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● A population will decrease to extinction when the instantaneous death rate exceeds the instantaneous birth rate (r < 0). </span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black"> ● The smaller the value of r below 1, the faster the population will decrease to zero. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● A population will increase when resources are available and the instantaneous birth rate exceeds the instantaneous death rate (r > 0)</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black"> ● The larger the value that r exceeds 1, the faster the population can increase over time </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● A population will neither increase or decrease when the population growth rate equals 0 (either due to N = 0, or if the per capita birth and death rates are exactly balanced). For example, the per capita birth and death rates could become exactly balanced due to density dependence and/or to the effect of a stressor that reduces survival and/or reproduction (Caswell 2001, Vandermeer and Goldberg 2003, Gotelli 2008, Murray and Sandercock 2020). </span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Effects incurred on a population from a chemical or non-chemical stressor could have an impact directly upon birth rate (reproduction) and/or death rate (survival), thereby causing a decline in population growth rate. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● Example of direct effect on r: Exposure to 17b-trenbolone reduced reproduction (i.e., reduced b) in the fathead minnow over 21 days at water concentrations ranging from 0.0015 to about 41 mg/L (Ankley et al. 2001; Miller and Ankley 2004). </span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Alternatively, a stressor could indirectly impact survival and/or reproduction. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● Example of indirect effect on r: Exposure of non-sexually differentiated early life stage fathead minnow to the fungicide prochloraz has been shown to produce male-biased sex ratios based on gonad differentiation, and resulted in projected change in population growth rate (decrease in reproduction due to a decrease in females and thus recruitment) using a population model. (Holbech et al., 2012; Miller et al. 2022)</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Density dependence can be an important consideration:</span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● The effect of density dependence depends upon the quantity of resources present within a landscape. A change in available resources could increase or decrease the effect of density dependence and therefore cause a change in population growth rate via indirectly impacting survival and/or reproduction. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● This concept could be thought of in terms of community level interactions whereby one species is not impacted but a competitor species is impacted by a chemical stressor resulting in a greater availability of resources for the unimpacted species. In this scenario, the impacted species would experience a decline in population growth rate. The unimpacted species would experience an increase in population growth rate (due to a smaller density dependent effect upon population growth rate for that species). </span> </span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Closed versus open systems:</span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● The above discussion relates to closed systems (there is no movement of individuals between population sites) and thus a declining population growth rate cannot be augmented by immigration. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● When individuals depart (emigrate out of a population) the loss will diminish population growth rate. </span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Population growth rate applies to all organisms, both sexes, and all life stages.</span></span></span></span></p>
<p> </p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Population growth rate (instantaneous growth rate) can be measured by sampling a population over an interval of time (i.e. from time t = 0 to time t = 1). The interval of time should be selected to correspond to the life history of the species of interest (i.e. will be different for rapidly growing versus slow growing populations). The population growth rate, r, can be determined by taking the difference (subtracting) between the initial population size, N</span><sub><span style="font-size:9pt"><span style="color:black">t=0 </span></span></sub><span style="color:black">(population size at time t=0), and the population size at the end of the interval, N</span><sub><span style="font-size:9pt"><span style="color:black">t=1 </span></span></sub><span style="color:black">(population size at time t = 1), and then subsequently dividing by the initial population size. </span></span></span></span></p>
<p style="margin-left:96px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Equation 2: r = (N</span><sub><span style="font-size:9pt"><span style="color:black">t=1 </span></span></sub><span style="color:black">- N</span><sub><span style="font-size:9pt"><span style="color:black">t=0</span></span></sub><span style="color:black">) / N</span><sub><span style="font-size:9pt"><span style="color:black">t=0</span></span></sub></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">The diversity of forms, sizes, and life histories among species has led to the development of a vast number of field techniques for estimation of population size and thus population growth over time (Bookhout 1994, McComb et al. 2021). </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● For stationary species an observational strategy may involve dividing a habitat into units. After setting up the units, samples are performed throughout the habitat at a select number of units (determined using a statistical sampling design) over a time interval (at time t = 0 and again at time t = 1), and the total number of organisms within each unit are counted. The numbers recorded are assumed to be representative for the habitat overall, and can be used to estimate the population growth rate within the entire habitat over the time interval. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● For species that are mobile throughout a large range, a strategy such as using a mark-recapture method may be employed (i.e. tags, bands, transmitters) to determine a count over a time interval (at time = 0 and again at time =1). </span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Population growth rate can also be estimated using mathematical model constructs (for example, ranging from simple differential equations to complex age or stage structured matrix projection models and individual based modeling approaches), and may assume a linear or nonlinear population increase over time (Caswell 2001, Vandermeer and Goldberg 2003, Gotelli 2008, Murray and Sandercock 2020). The AOP framework can be used to support the translation of pathway-specific mechanistic data into responses relevant to population models and output from the population models, such as changing (declining) population growth rate, can be used to assess and manage risks of chemicals (Kramer et al. 2011). As such, this translational capability can increase the capacity and efficiency of safety assessments both for single chemicals and chemical mixtures (Kramer et al. 2011). </span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Some examples of modeling constructs used to investigate population growth rate:</span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● A modeling construct could be based upon laboratory toxicity tests to determine effect(s) that are then linked to the population model and used to estimate decline in population growth rate. Miller et al. (2007) used concentration–response data from short term reproductive assays with fathead minnow (<em>Pimephales promelas</em>) exposed to endocrine disrupting chemicals in combination with a population model to examine projected alterations in population growth rate. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● A model construct could be based upon a combination of effects-based monitoring at field sites (informed by an AOP) and a population model. Miller et al. (2015) applied a population model informed by an AOP to project declines in population growth rate for white suckers (Catostomus commersoni) using observed changes in sex steroid synthesis in fish exposed to a complex pulp and paper mill effluent in Jackfish Bay, Ontario, Canada. Furthermore, a model construct could be comprised of a series of quantitative models using KERs that culminates in the estimation of change (decline) in population growth rate. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● A quantitative adverse outcome pathway (qAOP) has been defined as a mathematical construct that models the dose–response or response–response relationships of all KERs described in an AOP (Conolly et al. 2017, Perkins et al. 2019). Conolly et al. (2017) developed a qAOP using data generated with the aromatase inhibitor fadrozole as a stressor and then used it to predict potential population‐level impacts (including decline in population growth rate). The qAOP modeled aromatase inhibition (the molecular initiating event) leading to reproductive dysfunction in fathead minnow (Pimephales promelas) using 3 computational models: a hypothalamus–pituitary–gonadal axis model (based on ordinary differential equations) of aromatase inhibition leading to decreased vitellogenin production (Cheng et al. 2016), a stochastic model of oocyte growth dynamics relating vitellogenin levels to clutch size and spawning intervals (Watanabe et al. 2016), and a population model (Miller et al. 2007).</span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● Dynamic energy budget (DEB) models offer a methodology that reverse engineers stressor effects on growth, reproduction, and/or survival into modular characterizations related to the acquisition and processing of energy resources (Nisbet et al. 2000, Nisbet et al. 2011). Murphy et al. (2018) developed a conceptual model to link DEB and AOP models by interpreting AOP key events as measures of damage-inducing processes affecting DEB variables and rates.</span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● Endogenous Lifecycle Models (ELMs), capture the endogenous lifecycle processes of growth, development, survival, and reproduction and integrate these to estimate and predict expected fitness (Etterson and Ankley, 2021). AOPs can be used to inform ELMs of effects of chemical stressors on the vital rates that determine fitness, and to decide what hierarchical models of endogenous systems should be included within an ELM (Etterson and Ankley, 2021).</span></span></span></span></p>
<p> </p>
<p>Consideration of population size and changes in population size over time is potentially relevant to all living organisms.</p>
Not SpecifiedUnspecificNot SpecifiedAll life stagesHigh<ul>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Ankley GT, Jensen KM, Makynen EA, Kahl MD, Korte JJ, Hornung MW, Henry TR, Denny JS, Leino RL, Wilson VS, Cardon MD, Hartig PC, Gray LE. 2003. Effects of the androgenic growth promoter 17b-trenbolone on fecundity and reproductive endocrinology of the fathead minnow. Environ. Toxicol. Chem. 22: 1350–1360.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Bookhout TA. 1994. Research and management techniques for wildlife and habitats. The Wildlife Society, Bethesda, Maryland. 740 pp.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Caswell H. 2001. Matrix Population Models. Sinauer Associates, Inc., Sunderland, MA, USA</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Cheng WY, Zhang Q, Schroeder A, Villeneuve DL, Ankley GT, Conolly R. 2016. Computational modeling of plasma vitellogenin alterations in response to aromatase inhibition in fathead minnows. Toxicol Sci 154: 78–89.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Conolly RB, Ankley GT, Cheng W-Y, Mayo ML, Miller DH, Perkins EJ, Villeneuve DL, Watanabe KH. 2017. Quantitative adverse outcome pathways and their application to predictive toxicology. Environ. Sci. Technol. 51: 4661-4672.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Etterson MA, Ankley GT. 2021. Endogenous Lifecycle Models for Chemical Risk Assessment. Environ. Sci. Technol. 55: 15596-15608. </span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Gotelli NJ, 2008. A Primer of Ecology. Sinauer Associates, Inc., Sunderland, MA, USA.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Holbech H, Kinnberg KL, Brande-Lavridsen N, Bjerregaard P, Petersen GI, Norrgren L, Orn S, Braunbeck T, Baumann L, Bomke C, Dorgerloh M, Bruns E, Ruehl-Fehlert C, Green JW, Springer TA, Gourmelon A. 2012 Comparison of zebrafish (<em>Danio rerio</em>) and fathead minnow <em>(Pimephales promelas</em>) as test species in the Fish Sexual Development Test (FSDT). Comp. Biochem. Physiol. C Toxicol. Pharmacol. 155: 407–415.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Kramer VJ, Etterson MA, Hecker M, Murphy CA, Roesijadi G, Spade DJ, Stromberg JA, Wang M, Ankley GT. </span><span style="color:black">2011. Adverse outcome pathways and risk assessment: Bridging to population level effects. Environ. Toxicol. Chem. 30, 64-76.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">McComb B, Zuckerberg B, Vesely D, Jordan C. 2021. Monitoring Animal Populations and their Habitats: A Practitioner's Guide. Pressbooks, Oregon State University, Corvallis, OR Version 1.13, 296 pp. </span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Miller DH, Villeneuve DL, Santana Rodriguez KJ, Ankley GT. 2022. A multidimensional matrix model for predicting the effect of male biased sex ratios on fish populations. Environmental Toxicology and Chemistry 41(4): 1066-1077.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Miller DH, Tietge JE, McMaster ME, Munkittrick KR, Xia X, Griesmer DA, Ankley GT. 2015. </span><span style="color:black">Linking mechanistic toxicology to population models in forecasting recovery from chemical stress: A case study from Jackfish Bay, Ontario, Canada. Environmental Toxicology and Chemistry 34(7): 1623-1633.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Miller DH, Jensen KM, Villeneuve DE, Kahl MD, Makynen EA, Durhan EJ, Ankley GT. 2007. </span><span style="color:black">Linkage of biochemical responses to population-level effects: A case study with vitellogenin in the fathead minnow (<em>Pimephales promelas</em>). Environ Toxicol Chem 26: 521–527.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Miller DH, Ankley GT. 2004. Modeling impacts on populations: Fathead minnow (<em>Pimephales promelas</em>) exposure to the endocrine disruptor 17b-trenbolone as a case study. Ecotox Environ Saf 59: 1–9.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Murphy CA, Nisbet RM, Antczak P, Garcia-Reyero N, Gergs A, Lika K, Mathews T, Muller EB, Nacci D, Peace A, Remien CH, Schultz IR, Stevenson LM, Watanabe KH. 2018. Incorporating suborganismal processes into dynamic energy budget models for ecological risk assessment. Integrated Environmental Assessment and Management 14(5): 615–624.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Murray DL, Sandercock BK (editors). 2020. Population ecology in practice. Wiley-Blackwell, Oxford UK, 448 pp.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Nisbet RM, Jusup M, Klanjscek T, Pecquerie L. 2011. Integrating dynamic energy budget (DEB) theory with traditional bioenergetic models. The Journal of Experimental Biology 215: 892-902.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Nisbet RM, Muller EB, Lika K, Kooijman SALM. 2000. </span><span style="color:black">From molecules to ecosystems through dynamic energy budgets. J Anim Ecol 69: 913–926.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Perkins EJ, Ashauer R, Burgoon L, Conolly R, Landesmann B,, Mackay C, Murphy CA, Pollesch N, Wheeler JR, Zupanic A, Scholzk S. 2019. Building and applying quantitative adverse outcome pathway models for chemical hazard and risk assessment. Environmental Toxicology and Chemistry 38(9): 1850–1865. </span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Vandermeer JH, Goldberg DE. 2003. Population ecology: first principles. Princeton University Press, Princeton NJ, 304 pp.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Villeneuve DL, Crump D, Garcia-Reyero N, Hecker M, Hutchinson TH, LaLone CA, Landesmann B, Lattieri T, Munn S, Nepelska M, Ottinger MA, Vergauwen L, Whelan M. Adverse outcome pathway (AOP) development 1: Strategies and principles. Toxicol Sci. 2014: 142:312–320</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Watanabe KH, Mayo M, Jensen KM, Villeneuve DL, Ankley GT, Perkins EJ. 2016. Predicting fecundity of fathead minnows (<em>Pimephales promelas</em>) exposed to endocrine‐disrupting chemicals using a MATLAB(R)‐based model of oocyte growth dynamics. PLoS One 11: e0146594.</span></span></span></li>
</ul>
2016-11-29T18:41:242023-01-03T09:09:06505523c8-d81f-4ddd-bb85-7bc1d3eff2287b9e274a-1cdb-46e8-a09a-ec73ea0a2b482019-05-22T05:13:502019-05-22T05:13:507b9e274a-1cdb-46e8-a09a-ec73ea0a2b484852e8f8-ed9a-49a3-bbc5-5857ba352e7a2019-05-22T05:14:202019-05-22T05:14:204852e8f8-ed9a-49a3-bbc5-5857ba352e7a54c3eb93-3a9d-4e35-b3e0-da8d618988a42019-05-22T05:14:412019-05-22T05:14:4154c3eb93-3a9d-4e35-b3e0-da8d618988a4e9d5f5ef-1b06-48d2-ae85-8ffa17e10331<p><strong>Photoreceptors in the retina of vertebrates and invertebrates are the cells that are responsible for phototransduction. Photoreceptor subtypes are characterized by different opsins (light-sensitive proteins) that respond to light with different wavelengths. The pattern of photoreceptors in the eyes therefore determines visual function. Alterations in photoreceptor patterning could include altered numbers of photoreceptor subtypes leading to an altered ratio of photoreceptor subtypes and/or altered spatial organization.</strong></p>
<p dir="ltr"><strong>Since different photoreceptor subtypes have different opsins that allow for perceiving light of different wavelengths, it is plausible to assume that alterations in photoreceptor patterning such as altered ratios of photoreceptor subtypes affect normal visual function.</strong></p>
<p><br />
</p>
<ul>
<li dir="ltr">
<p dir="ltr"><strong>Flamarique et al. (2013) used thyroid hormone treatment to transform the UV cones of young rainbow trout into blue cones and showed that this reduced the distances and angles at which prey were located (variables that are known indicators of foraging performance). Using optical measurements and photon-catch calculations, the study showed that control rainbow trouts perceived Daphnia with greater contrast compared to thyroid-hormone-treated fish, demonstrating that the presence of UV cones enhances foraging performance of young rainbow trout.</strong></p>
</li>
<li dir="ltr">
<p dir="ltr"><strong>Houbrechts et al. (2016) used a knockdown of deiodinase 1 and 2 in zebrafish embryos to induce transient hypothyroidism and observed decreased levels of mRNA coding for rod and cone opsins (at 3 dpf, days post fertilization) and a strong transient reduction in rods and all four cone types (at 3 dpf but no longer at 7 dpf) together with a transiently reduced response (increase of swimming activity) to light (4 dpf, but no longer at 7 dpf).</strong></p>
</li>
<li dir="ltr">
<p dir="ltr"><strong>Van Camp et al. (2019) showed that permanent deiodinase 2 deficiency resulted in a reduction of the number of R/G cones and rods that persisted through 7 dpf together with a reduced response to light (observed at 6 dpf). </strong></p>
</li>
<li dir="ltr">
<p dir="ltr"><strong>Frau et al. (2020) studied the consequences of differences in photoreceptor patterning across fish species. They concluded that species that are primarily nocturnal or live in low light environments such as the common sole and Senegalese sole have a less ordered mosaic cone pattern. A study of different fish species reveiled that lattice-like patterning of the cone mosaic seems to improve visual acuity. Fish taxa that live in low light environments generally do not possess lattice-like cone mosaics.</strong></p>
</li>
</ul>
Not Specified<ol>
<li dir="ltr">
<p dir="ltr"><strong>Taxonomic</strong></p>
</li>
</ol>
<p dir="ltr"><strong>Although there are important taxonomic differences in opsin genes and in photoreceptor patterning across taxa, it is plausible to assume that the importance of proper photoreceptor patterning for normal visual function is applicable across all vertebrates and invertebrates that have eyes.</strong></p>
<ol start="2">
<li dir="ltr">
<p dir="ltr"><strong>Life stage</strong></p>
</li>
</ol>
<p dir="ltr"><strong>It is plausible to assume that alterations of photoreceptor patterning would result in altered visual function across all life stages, but such alterations are most likely to occur during the development of the normal photoreceptor pattern, which occurs in the embryonic phase. </strong></p>
<ol start="3">
<li dir="ltr">
<p dir="ltr"><strong>Sex</strong></p>
</li>
</ol>
<p dir="ltr"><strong>Zebrafish are undifferentiated gonochorists since both sexes initially develop an immature ovary (Maack and Segner, 2003). Immature ovary development progresses until approximately the onset of the third week. Later, in female fish immature ovaries continue to develop further, while male fish undergo transformation of ovaries into testes. Final transformation into testes varies among male individuals, however finishes usually around 6 weeks post fertilization. Effects on visual function resulting from altered photoreceptor patterning during early development are therefore expected to be independent of sex.</strong></p>
<p><br />
</p>
<p dir="ltr"><strong>Flamarique, I.N., 2013. Opsin switch reveals function of the ultraviolet cone in fish foraging. Proceedings of the Royal Society B-Biological Sciences 280.</strong></p>
<p dir="ltr"><strong>Frau, S., Flamarique, I.N., Keeley, P.W., Reese, B.E., Munoz-Cueto, J.A., 2020. Straying from the flatfish retinal plan: Cone photoreceptor patterning in the common sole (Solea solea) and the Senegalese sole (Solea senegalensis). Journal of Comparative Neurology 528, 2283-2307.</strong></p>
<p dir="ltr"><strong>Houbrechts, A.M., Vergauwen, L., Bagci, E., Van Houcke, J., Heijlen, M., Kulemeka, B., Hyde, D.R., Knapen, D., Darras, V.M., 2016. Deiodinase knockdown affects zebrafish eye development at the level of gene expression, morphology and function. Molecular and Cellular Endocrinology 424, 81-93.</strong></p>
<p dir="ltr"><strong>Maack, G., Segner, H., 2003. Morphological development of the gonads in zebrafish. Journal of Fish Biology 62, 895-906.</strong></p>
<p dir="ltr"><strong>Vancamp, P., Houbrechts, A.M., Darras, V.M., 2019. Insights from zebrafish deficiency models to understand the impact of local thyroid hormone regulator action on early development. General and Comparative Endocrinology 279, 45-52.</strong></p>
<p><br />
</p>
2019-05-22T05:15:392021-06-16T07:24:33e9d5f5ef-1b06-48d2-ae85-8ffa17e103312c0a6b20-5f75-4eec-a0a1-7d80a3f15abbNot Specified2020-05-25T10:50:242020-05-25T10:50:24Inhibition of retinaldehyde dehydrogenase leads to population declineretinaldehyde dehydrogenase inhibition,population decline<p><span style="font-size:12px"><span style="color:#000000">Cho,Kichul (</span><a href="mailto:kichul.cho@kist-europe.de"><span style="color:#000000">kichul.cho@mabik.re.kr </span></a><span style="color:#000000">)</span></span></p>
<p><span style="color:#000000"><span style="font-size:12px">Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe, Campus E 7.1, 66123 Saarbruecken, Germany</span></span></p>
<p><span style="font-size:12px"><span style="color:#000000">Ryu, Chang Seon (</span><a href="mailto:changryu@kist-europe.de"><span style="color:#000000">changryu@kist-europe.de</span></a><span style="color:#000000">)</span></span></p>
<p><span style="color:#000000"><span style="font-size:12px">Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe, Campus E 7.1, 66123 Saarbruecken, Germany</span></span></p>
<p><span style="font-size:12px"><span style="color:#000000">Sung, Baeckkyoung <u>(</u>sung@kist-europe.de<u>)</u></span></span></p>
<p><span style="font-size:10px">Park Chang-Beom, Korea Institute of Toxicology JRC-APT (Joint Research Center for Alternative and Predictive Toxicology)</span></p>
<p><span style="font-size:10px"><span style="color:#000000">Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe, Campus E 7.1, 66123 Saarbruecken, Germany</span></span></p>
<p><span style="font-size:10px"><span style="color:#000000">Baik, Seung yun (</span><a href="mailto:sbaik@kist-europe.de"><span style="color:#000000">sbaik@kist-europe.de</span></a><span style="color:#000000">)</span></span></p>
<p><span style="font-size:10px"><span style="color:#000000">Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe, Campus E 7.1, 66123 Saarbruecken, Germany</span></span></p>
<p><span style="font-size:10px"><span style="color:#000000">Kim, Youngjun (</span><a href="mailto:youngjunkim@kist-europe.de"><span style="color:#000000">youngjunkim@kist-europe.de</span></a><span style="color:#000000">)</span></span></p>
<p><span style="font-size:10px"><span style="color:#000000">Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe, Campus E 7.1, 66123 Saarbruecken, Germany</span></span></p>
Under Development: Contributions and Comments WelcomeUnder DevelopmentIncluded in OECD Work Plan1.77<p>The present AOP is designed to estimate potential AO of fishes results from the retinaldehyde dehydrogenase (RALDH) inhibition. Visual impairment results from eye development of an embryonic cell might lead to population decline which is the potential endpoint. This AOP will provide a useful risk assessment tool for the toxic assessment of chemicals. Furthermore, this AOP can be applied to the prediction of eco-toxicity caused by the inhibition of RALDH.</p>
<table align="left" cellpadding="0" cellspacing="0">
<tbody>
<tr>
<td>
<p>This adverse outcome pathway (AOP) represents the potential causative adverse outcomes (AOs) by inhibition of retinaldehyde dehydrogenase (RALDH), which is one of the crucial enzymes participating in retinol metabolism. The role of RALDH in retinol metabolism is to catalyze the chemical reaction converting retinal to retinoic acid (RA). The synthesized RA is associated with the cellular RA-binding protein (CRABP) and enters into the nucleus, and then bind to retinoic acid receptors (RARs) along with retinoid X receptors (RXRs) (Vilhais-Neto and Pourquié, 2008). The activated RARs and RXRs can act as target gene transcription factors regulating embryonic development in fishes (Perz-Edwards et al., 2011). Inhibition of RALDH can be caused by chemical inhibitors such as Disulphiram, Citral, Paclobutrazol, Diethylaminobenzaldehyde, Nitrofen, 4-biphenyl carboxylic acid, Bisdiamine, SB-210661 and etc. (Marsh-Armstrong et al., 1994; Chawla et al., 2018; Wang et al., 2017; Le et al., 2012; Mey et al., 2003). RALDH inhibition, the molecular initiating event (MIE) for this AOP, leads to decreased RA synthesis blocking the reaction converting retinal to RA in embryonic cells (Hyatt and Dowling, 1997; Molotkov et al., 2002; Le et al., 2012; Duester, 2009). Since RA is an essential activator for the RARs and RXRs-mediated gene transcription, low level of plasma RA leads to abnormal development in embryonic cells. A number of previous studies well-elucidated the abnormal developments by RA inhibition including visual function and eye development (Duester et al., 2009; Hyatt and Dowling, 1997; Hyatt et al., 1996; Kam et al., 2012; Le et al., 2012; Luo et al., 2006; Marsh-Armstrong et al., 1994; Matt et al., 2005; Wang et al., 2017), intestinal development (Nadauld et al., 2005), brain patterning and neurogenesis (Begemann et al., 2004; Niederreither and Dollé, 2008; Samarut et al., 2015), and heart development (Niederreither and Dollé, 2008; Samarut et al., 2015). The development of early embryonic cells of fishes plays an essential role in the organism’s young of year survival and adaptation in fluctuated environmental condition. The impact of the development of the optical elements of the eye by RALDH inhibition in fish population trajectory has not been clarified yet, although the importance of the visual function of fishes previously mentioned by previous studies (Fernald, 1984; Sandström, 1999).</p>
<p><strong>Acknowledgements</strong>: This research was supported by the National Research Council of Science & Technology(NST) grant by the Korea government (MSIP) (No. CAP-17-01-KIST Europe)</p>
</td>
</tr>
</tbody>
</table>
<div> </div>
<p>Maintenance of sustainable fish and wildlife populations (i.e., adequate to ensure long-term delivery of valued ecosystem services) is a widely accepted regulatory goal upon which risk assessments and risk management decisions are based.</p>
adjacentNot SpecifiedHighadjacentNot SpecifiedHighadjacentNot SpecifiedHighadjacentModerateModerateadjacentLowLowModerateMixedModerateBirth to < 1 monthModerate<p>This AOP is under development supported by the National Research Council of Science & Technology (NST) grant by the Korea government (MSIP) (No. CAP-17-01-KIST Europe) and P11911.</p>
<p> </p>
<table border="1" cellpadding="0" cellspacing="0" style="width:841px">
<tbody>
<tr>
<td colspan="2" style="height:17px; width:463px">
<p><strong><u>To do</u></strong></p>
</td>
<td style="height:17px; width:97px">
<p><strong><u>Expected duration</u></strong></p>
</td>
</tr>
<tr>
<td rowspan="2" style="height:16px; width:168px">
<p>Building the AOP frame</p>
</td>
<td style="height:16px; width:294px">
<p>Development of KEs</p>
</td>
<td style="height:16px; width:97px">
<p>3 month</p>
</td>
</tr>
<tr>
<td style="height:17px; width:294px">
<p>Production of experimental data</p>
</td>
<td style="height:17px; width:97px">
<p>18 month</p>
</td>
</tr>
<tr>
<td rowspan="5" style="height:16px; width:168px">
<p>Overall assessment of the AOP</p>
</td>
<td style="height:16px; width:294px">
<p>Biological domain of applicability</p>
</td>
<td style="height:16px; width:97px">
<p>3 month</p>
</td>
</tr>
<tr>
<td style="height:17px; width:294px">
<p>Essentiality of all KEs</p>
</td>
<td style="height:17px; width:97px">
<p>3 month</p>
</td>
</tr>
<tr>
<td style="height:16px; width:294px">
<p>Evidence supporting all KERs</p>
</td>
<td style="height:16px; width:97px">
<p>5 month</p>
</td>
</tr>
<tr>
<td style="height:17px; width:294px">
<p>Quantitative WoE considerations</p>
</td>
<td style="height:17px; width:97px">
<p>5 month</p>
</td>
</tr>
<tr>
<td style="height:17px; width:294px">
<p>Quantitative understanding for each KER</p>
</td>
<td style="height:17px; width:97px">
<p>6 month</p>
</td>
</tr>
</tbody>
</table>
<p><em>The roles of RALDH play in sensory perception of fish mating opportunities via their presence in the visual functions. Significantly, the AO (population decline) can apply to IATA by dysfunction of the retinoid in reproduction in the aquatic environment. It can be applied to</em> <em>retinoid effects on a central nervous system within the OECD EDTA</em></p>
HighHighHighHighHighHighHighHigh<ol>
<li>Chawla, B., Swain, W., Williams, A. L., & Bohnsack, B. L. (2018). Retinoic Acid Maintains Function of Neural Crest–Derived Ocular and Craniofacial Structures in Adult Zebrafish. Investigative ophthalmology & visual science, 59(5), 1924-1935.</li>
<li>Duester, G. (2009). Keeping an eye on retinoic acid signaling during eye development. Chemico-biological interactions, 178(1-3), 178-181.</li>
<li>Fernald, R. D. (1984). Vision and Behavior in an African Cichlid fish: Combining behavioral and physiological analyses reveals how good vision is maintained during rapid growth of the eyes. American Scientist, 72(1), 58-65.</li>
<li>Hyatt, G. A., Schmitt, E. A., Marsh-Armstrong, N., McCaffery, P., Drager, U. C., & Dowling, J. E. (1996). Retinoic acid establishes ventral retinal characteristics. Development, 122(1), 195-204.</li>
<li>Hyatt, G. A., & Dowling, J. E. (1997). Retinoic acid. A key molecule for eye and photoreceptor development. Investigative ophthalmology & visual science, 38(8), 1471-1475.</li>
<li>Kam, R. K. T., Deng, Y., Chen, Y., & Zhao, H. (2012). Retinoic acid synthesis and functions in early embryonic development. Cell & bioscience, 2(1), 11.</li>
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