Adverse Outcome Pathway on Deposition of Energy Leading to Cataracts

The present Adverse Outcome Pathway (AOP) describes the development of cataracts following ionizing radiation exposure, beginning with the deposition of energy into cells of the eye. This event generates an excess of reactive oxygen species, leading to oxidative stress when the balance between oxidants and antioxidants is disrupted. Oxidative stress can damage critical macromolecules, particularly proteins such as crystallins in the lens, which may become structurally altered and aggregate. If these damaged proteins are not removed, they accumulate and cause lens opacity. Simultaneously, radiation-induced oxidative stress can damage DNA, leading to strand breaks and, if not adequately repaired, an increase in mutations and chromosomal abnormalities. When such genetic damage affects genes controlling cell proliferation, it can promote uncontrolled division of lens epithelial cells, further contributing to cataract formation. This AOP is supported by high biological plausibility and moderate evidence for the essentiality of key events. However, there is limited quantitative understanding of dose-response relationships. Despite these limitations, this AOP provides valuable insight for evaluating ocular risks of radiation exposure and guiding radiological protection efforts.