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Key Event Title
Altered, Visual function
|Level of Biological Organization|
Key Event Components
|vision trait||eye||functional change|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|retinaldehyde dehydrogenase inhibition,population decline||KeyEvent||Young Jun Kim (send email)||Under Development: Contributions and Comments Welcome||Under Development|
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|TPOi retinal layer structure||KeyEvent||Lucia Vergauwen (send email)||Open for citation & comment||EAGMST Under Review|
|TPOi eye size||KeyEvent||Lucia Vergauwen (send email)||Under development: Not open for comment. Do not cite||Under Development|
|TPOi photoreceptor patterning||KeyEvent||Lucia Vergauwen (send email)||Under development: Not open for comment. Do not cite||Under Development|
Key Event Description
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).
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).
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).
How It Is Measured or Detected
Measurements of visual function can be performed at the level of neuronal activity:
- Electroretinography (Chrispell et al., 2015)
- 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).
- 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.
Other measurements are performed at the level of the eyes:
- 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.
Yet other studies use assessment of vision-related behaviours:
- 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)).
- Light-dark transition or vision startle response: reaction to change in light intensity (light sensitivity) (Brastrom et al., 2019)
- Black-white preference test (Baumann et al., 2016)
- 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).
Domain of Applicability
Taxonomic applicability: Visual function decrease can be evaluated in a wide range of species including mammals, amphibians, fish and humans. Evaluation of these visual function modifications change according to the species and its environment.
Life-stage applicability: 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). 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).
Sex applicability: 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).
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
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
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
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
Chrispell JD, Rebrik TI, Weiss ER. 2015. Electroretinogram Analysis of the Visual Response in Zebrafish Larvae. Jove-Journal of Visualized Experiments(97).
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
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.
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.
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.2017.10.003
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
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
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
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
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
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
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
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.
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
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
Strauss, O. (2005). The retinal pigment epithelium in visual function. Physiological Reviews, 85(3), 845–881.https://doi.org/10.1152/physrev.00021.2004
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
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
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
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