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Event: 2083

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Occurrence of Cataracts

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Cataracts
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Organ

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
eye opacity Lens increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Deposition of energy leading to cataracts AdverseOutcome Vinita Chauhan (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
human Homo sapiens High NCBI
rat Rattus norvegicus High NCBI
mouse Mus musculus High NCBI
rabbit Oryctolagus cuniculus High NCBI
Monkey Monkey Moderate NCBI
Pig Pig Moderate NCBI
guinea pig Cavia porcellus Moderate NCBI
rainbow trout Oncorhynchus mykiss Moderate NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
All life stages High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Female High
Male High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Cataracts are a condition where the lens of the eye develops opacities and becomes cloudy, resulting in blurred vision as well as glare and haloes around lights (Liu et al., 2017). It is one of the leading causes of blindness around the world (Raj et al., 2009; Liu et al., 2017), and surgery is currently the only cure.  

The lens is a transparent, biconvex tissue located at the front of the eye. It is responsible for focusing light onto the retina, producing a clear image. However, under certain conditions, sections of the lens may develop small opacities, losing their transparency and resulting in blurred vision (Hildreth et al., 2009). As the lens has low metabolic and mitotic activity, there is very little tissue turnover. Therefore, opacities are not removed and accumulate with time (Hamada, 2017).  

A variety of factors are essential for maintaining the transparency of the lens, and therefore preventing cataracts. These include proper organization of proteins such as crystallins (Hildreth et al., 2009; Ainsbury et al., 2016; Hamada, 2017; Wu et al., 2018), no organelles within the lens fiber cells (Pendergrass, 2010; Fujimichi et al., 2014; Hamada, 2017), and a low water content in the lens (Ainsbury et al., 2016). Genetic factors can also play a role, such as mutations in genes coding for molecular chaperones, growth factors, gap-junction proteins, intermediated filament proteins, membrane proteins, and RNA binding proteins (Hamada & Fujimichi, 2015; Lachke, 2022). When any of these factors are affected, it causes light scattering, which increases lens opacity, contributing to cataract formation and intensity.  

In general, there are three main categories of cataract: pediatric, age-related and those secondary to other causes. Age-related cataracts are the most common and can be subdivided into nuclear, cortical, or posterior subcapsular cataracts based on which portion of the lens becomes opaque. In nuclear cataracts the opacities are in the nucleus of the lens, in cortical cataracts they are in the cortex, and in posterior subcapsular cataracts they are located beneath the posterior capsule (Van Kuijk, 1991).  

Cataracts can be diagnosed through several different methods and there is no universally accepted grading system. The most common grading systems are the Lens Opacities Classification System I, II, or III (LOC I, II, or III), the Modified Merriam-Focht Cataract Scoring System, and the slit lamp grading system. They classify cataracts on a scale of severity, which is often subjective, relying upon the examiner’s judgement (Barraquer et al., 2017). 

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Listed below are common methods for detecting the KE, however there may be other comparable methods that are not listed. 

Assay 

Reference 

Description 

OECD Approved Assay 

Lens opacification grading systems 

Barraquer et al., 2017 

Systems used to classify the severity of cataracts. There are multiple types including: the Modified Merriam-Focht Cataract Scoring System, Lens Opacities Classification System III (LOC III), Word Health Organization Cataract Grading System, Lens Opacities Classification System I (LOCI), Lens Opacities Classification System II (LOC II), Wisconsin Clinical and Photographic Cataract Grading System, Wilmer Clinical and Photographic Grading System, Oxford Clinical Cataract Grading System, Age-Related Eye Disease Study, National Eye Institute Clinical Cataract Grading System, Japanese Cooperative Cataract Research Group Cataract Grading System 

No 

Slit Lamp Grading System 

Barraquer et al., 2017; Robert & Alastair, 2017 

Measures the light intensity reflected from opacities in nuclear cataracts. This also includes various techniques such as retroillumination.  

No 

Microscopy Examination 

Stirling and Griffiths, 1991 

Tests can help to examine interlocking processes and membrane architecture of lens. 

No 

Histological staining 

Singh et al., 2003 

Uses dyes such as trypan blue to differentiate different parts of the lens. 

No 

Optical coherence tomography (OCT) 

Sharma, 2016 

Optical signals are sent towards a tissue, where they either pass through or are reflected. These signals are then interpreted to build a spatial image of the tissue. 

No 

Scheimpflug imaging 

Singh Grewal & Singh Grewal, 2012 

This technique allows for the photography of obliquely tilted specimens without losing focus. Cataract grading systems that utilize this principle include the Oxford Scheimpflug System, the Nidek EAS-1000, and the Zeiss Schfeimpflug video camera. 

No 

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Taxonomic applicability: This KE is relevant to any species requiring a clear lens for vision. 

Life stage applicability: This key event can occur at any life stage; however, it is most common in older adults. Among humans, cataract changes usually begin after the age of 50 and become increasingly prevalent with age.  

Sex applicability: Females have a small increased background risk of cataracts (Ainsbury et al., 2016). Females also have a higher risk for radiation induced cataracts including PSC, cortical and nuclear cataracts (Choshi et al., 1983, Nakashima et al., 2006; Henderson et al., 2010; Dynlacht et al., 2011; Azizova et al. 2018; Little et al., 2018; Garrett et al., 2020).  

Evidence for perturbation by prototypic stressors: A large body of evidence supports cataract induction via both ionizing and non-ionizing radiation. This includes X-rays, γ-rays, UV, neutrons, protons, β particles, and various heavy ions (56Fe, 40Ar, 12C, 20Ne, 224Ra, and He). Of these, X-rays and γ-rays are the best supported (Yang & Ainsworth, 1987; Chmelevsky, 1988l; Brenner et al., 1991; Fedorenko, 1995; Char et al., 1998; Nakashima et al., 2006; Worgul et al., 2007; Davis et al., 2010; Karatasakis et al., 2018; Garrett et al., 2020; Kang et al., 2020; McCarron et al., 2021).  

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

References

List of the literature that was cited for this KE description. More help

Ainsbury, E. A. et al. (2016), “Ionizing radiation induced cataracts: recent biological and mechanistic developments and perspectives for future research”, Mutation research. Reviews in mutation research, Vol. 770, Elsevier B.V., https://doi.org/10.1016/j.mrrev.2016.07.010  

Barraquer, R. I. et al. (2017), “Validation of the nuclear cataract grading system BCN 10”, Ophthalmic Research, Vol. 57/4, Karger, https://doi.org/10.1159/000456720  

Brenner, D. J. et al. (1991), “Accelerated heavy particles and the lens: VI. RBE studies at low doses”, Radiation Research, Vol. 128/1, Academic Press, Inc, United States, https://doi.org/10.2307/3578069  

Char, D. H., S. M. Kroll, and J. Castro (1998), “Ten-year follow-up of helium ion therapy for uveal melanoma”, American Journal of Ophthalmology, Vol. 125/1, Elsevier Inc, New York, https://doi.org/10.1016/S0002-9394(99)80238-4  

Chmelevsky, D et al. (1988), “An epidemiological assessment of lens opacifications that impaired vision in patients injected with radium-224”, Radiation Research, Vol. 115/2, Academic Press, Oak Brook, https://doi.org/10.2307/3577161  

Choshi, K et al. (1983), “Ophthalmologic changes related to radiation exposure and age in adult health study sample, Hiroshima and Nagasaki”, Radiation Research, Vol. 96/3, Academic Press, Oak Brook, https://doi.org/10.2307/3576122  

Davis, J. G et al. (2010), “Dietary supplements reduce the cataractogenic potential of proton and HZE-particle radiation in mice”, Radiation Research, Vol. 173/3, The Radiation Research Society, United States, https://doi.org/10.1667/RR1398.1  

Dynlacht, J. R et al. (2011), “Age and hormonal status as determinants of cataractogenesis induced by ionizing radiation. I. Densely ionizing (high-LET) radiation”, Radiation Research, Vol. 175/1, The Radiation Research Society, United States, https://doi.org/10.1667/RR2319.1  

Fujimichi, Y., N. Hamada and M. Duncan (2014), “Ionizing irradiation not only inactivates clonogenic potential in primary normal human diploid lens epithelial cells but also stimulates cell proliferation in a subset of this population”, PloS one, Vol. 9/5, Public Library of Science, United States, https://doi.org/10.1371/journal.pone.0098154  

Garrett, J et al. (2020), “The protective effect of estrogen against radiation cataractogenesis is dependent upon the type of radiation”, Radiation Research, Vol. 194/5, Radiation Research Society, United States, https://doi.org/10.1667/RADE-20-00015.1  

Hamada, N. (2015), “Role of carcinogenesis related mechanisms in cataractogenesis and its implications for ionizing radiation cataractogenesis.” Cancer letters, Vol. 368,2 . https://doi.org/10.1016/j.canlet.2015.02.017  

Hamada, N. (2017), “Ionizing radiation sensitivity of the ocular lens and its dose rate dependence”, International journal of radiation biology, Vol. 93/10, Taylor & Francis, England, https://doi.org/10.1080/09553002.2016.1266407  

Hausmann, J. C. et al. (2020), “Ophthalmic examination findings and intraocular pressure measurements in six species of Anura”, Journal of Zoo and Wildlife Medicine, Vol. 50/4, American Association of Zoo Veterinarians, United States, https://doi.org/10.1638/2019-0115  

Henderson, M. A. et al. (2010), “Effects of estrogen and gender on cataractogenesis induced by high-let radiation” Radiation Research, Vol. 173/2, The Radiation Research Society, United States, https://doi.org/10.1667/RR1917.1  

Hildreth, C. J., A. E. Burke, and R. M. Glass (2009), “Cataracts”, JAMA: the journal of the American Medical Association, Vol. 301/19, https://doi.org/10.1001/jama.301.19.2060  

Kang, L. H. et al. (2020), “Ganoderic acid A protects lens epithelial cells from UVB irradiation and delays lens opacity”, Chinese Journal of Natural Medicines, Vol. 18/12, Elsevier B. V., China, https://doi.org/10.1016/S1875-5364(20)60037-1  

Karatasakis, A. et al. (2018), “Radiation-associated lens changes in the cardiac catheterization laboratory: Results from the IC-CATARACT (CATaracts Attributed to Radiation in the CaTh lab) study”, Catheterization and Cardiovascular Interventions, Vol. 91/4, Wiley Subscription Services, United States, https://doi.org/10.1002/ccd.27173  

Lachke, S. A. (2022), “RNA-binding proteins and post-transcriptional regulation in lens biology and cataract: mediating spatiotemporal expression of key factors that control the cell cycle, transcription, cytoskeleton and transparency”, Experimental Eye Research, Vol. 214, Elsevier Ltd, England, https://doi.org/10.1016/j.exer.2021.108889  

Little, M. P. et al. (2018), “Occupational radiation exposure and risk of cataract incidence in a cohort of US radiologic technologists”, European Journal of Epidemiology, Vol. 33/12, Springer, https://doi.org/10.1007/s10654-018-0435-3.  

Liu, Y. et al. (2017), “Cataracts”, The Lancet (British edition), Vol. 390/10094, Elsevier Ltd, England, https://doi.org/10.1016/S0140-6736(17)30544-5  

McCarron, R. A. et al. (2021), “Radiation-induced lens opacity and cataractogenesis: a lifetime study using mice of varying genetic backgrounds”, Radiation research, Vol. 197/1, Radiation Research Society, United States, https://doi.org/10.1667/RADE-20-00266.1  

Nakashima, E. et al. (2006), “A reanalysis of atomic-bomb cataract data, 2000-2002: A threshold analysis”, Health Physics, Vol. 90/2, Health Physics Society, Philadelphia, https://doi.org/10.1097/01.HP.0000175442.03596.63  

Pendergrass, W. et al. (2010), “X-ray induced cataract is preceded by LEC loss, and coincident with accumulation of cortical DNA, and ROS; similarities with age-related cataracts”, Molecular vision, Vol. 16, Molecular Vision, United States, pp. 1496-1513  

Raj et al. (2009), “Post-operative capsular opacification”, Nepalese journal of ophthalmology, Nepal, https://doi.org/10.3126/nepjoph.v1i1.3673  

Singh, A. J. et al. (2003), “A histological analysis of lens capsules stained with trypan blue doe capsulorrhexis in phacoemulsification cataract surgery”, Eye, Vol. 17/5, Springer Nature, London, https://doi.org/10.1038/sj.eye.6700440  

Sing Grewal, D. and S. P. Singh Grewal (2012), “Clinical applications of Scheimpflug imaging in cataract surgery”, Saudi Journal of Ophthalmology, Vol. 26, Elsevier, pp. 25-32  

Stirling, R.J. and P. G. Griffiths (1991), “Scanning EM studies of normal human lens fibres and fibres from nuclear cataracts”, Eye, Vol. 5/1, Springer Nature, London, https://doi.org/10.1038/eye.1991.17  

Worgul, B. V et al. (2007), “Cataracts among Chernobyl clean-up workers: Implications regarding permissible eye exposures”, Radiation Research, Vol. 167/2, Radiation Research Society, Lawrence, https://doi.org/10.1667/RR0298.1  

Wu, Shu-Yu et al. (2018), “Transgenic zebrafish models reveal distinct molecular mechanisms for cataract-linked αA-crystallin mutants”, PloS One, Vol. 13/11, Public Library of Science, United States, https://doi.org/10.1371/journal.pone.0207540  

Yang, V. C. and E. J. Ainsworth (1987), “A histological study on the cataractogenic effects of heavy charged particles”, Vol. 11/1, National Science Council of the Republic of China, pp. 18-28