Occurrence of Cataracts

Cataracts are a progressive condition in which the lens of the eye develops opacities and becomes cloudy, resulting in blurred vision as well as glare and haloes around lights (National Eye Institute, 2022). For this AOP, a cataract is defined when over 5% of the lens is opacified. 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, damaged proteins that are not removed can acucmulate over time contributing to opacities and formation of cataracts (Hamada, 2017).  

A variety of factors are essential for maintaining the transparency of the lens, and therefore preventing cataracts. These include proper organization, development and balance of proteins such as crystallins (Hildreth et al., 2009; Ainsbury et al., 2016; Hamada, 2017; Wu et al., 2018), no organelles within the mature lens fiber cells (Pendergrass, 2010; Fujimichi et al., 2014; Hamada, 2017; Heitmancik & Shiels, 2015), 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 density.  

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 (PSC) 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).  Research has shown that posterior subcapsular (PSC) cataracts are a subtype of cataract that are most often found with ionizing radiation exposure. This may be due to radiation exposure causing the improperly differentiated lens epithelial cells (LECs) to leave the germinative zone (GZ) and migrate along the posterior capsule towards the center of the lens. As atypical lens fiber cells (LFCs), and atypical LECs accumulate in this area, they may cause the development of a PSC cataract (Loganovsky et al., 2020).

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. However, there are some methods such as Scheimpflug imaging which are less subjective as they measure lens density (Barraquer et al., 2017; Singh Grewal & Singh Grewal, 2012). 

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

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: The adverse outcome can develop in both sexes and is not sex-specific. Females, however, have a small increased background risk of cataracts (Ainsbury et al., 2016). They 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).  

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