Overexpression of Ku80 Protects Lens Epithelial Cells from Selenium-Induced Cataract Formation by Regulating the DNA Damage Response

PURPOSE: DNA damage and repair defects in lens epithelial cells (LECs) contribute to the formation and progression of age-related cataracts (ARC). Ku antigen 80 kDa (Ku80) plays an important role in the non-homologous end-joining (NHEJ) pathway for repairing DNA double-strand breaks, while the Cockayne Syndrome Complementary B (CSB) protein plays a critical role in the nucleotide excision repair pathway. This study evaluates the protective effect of AAV-mediated overexpression of Ku80 in rat LECs and explores its contribution to delaying selenium-induced cataract formation. METHODS: = 14). The AAV-Ku80 group received adenovirus-mediated overexpression of Ku80, the AAV-NC group received adenoviral vector negative control, and the control group was injected with physiological saline. All injections were performed in the anterior chamber. Except for the control group, the other two groups were subcutaneously injected with sodium selenite solution into the nape of the neck 30 min after the injection. The degree of lens opacity was examined using a slit-lamp, and lenses were harvested to assess antioxidant parameters, including superoxide dismutase (SOD) activity, reduced glutathione (GSH) content, and the oxidative damage marker malondialdehyde (MDA) content. Western blot analysis was performed to examine the upregulation of CSB protein and its association with delayed cataract formation. RESULTS: Overexpression of Ku80 significantly enhanced the expression of CSB protein, improved DNA repair capacity, and mitigated the influences of oxidative stress on rat LECs. This resulted in a significant increase in SOD and GSH levels, a significant decrease in MDA levels, and postponed the onset of selenium-induced cataracts, hence preserving lens clarity. Moreover, Ku80 overexpression partially alleviated damage to the corneal endothelium and retina. CONCLUSION: Ku80 overexpression alleviates damage to LECs and postpones the development of selenium-induced cataracts by increasing CSB protein levels and controlling DNA repair processes. This research underscores the significant therapeutic potential of Ku80 in postponing cataract formation and may offer new avenues for gene therapy in the prevention and treatment of cataracts.