Elevated level of uric acid in aqueous humour is associated with posterior subcapsular cataract in human lens

Importance Age-related cataract is the leading cause of blindness worldwide. The pathological mechanisms causing this disease remain elusive. Background To examine the involvement of uric acid (UA) in the pathogenesis of posterior subcapsular cataract (PSC). Design Retrospective study and experimental investigation. Participants A total of 180 patients with PSC or non-PSC were included. Methods Samples obtained from the patients were used to analyse content of UA and for histochemical examinations. The effects of UA on human lens epithelial cells were also investigated. Main Outcome Measures Aqueous humour UA and urate deposits. Results The results showed a significant increase of aqueous humour UA in patients with PSC. After adjustment for potential confounders, elevated aqueous humour UA (odds ratio [OR] = 1.45) showed a stronger association with PSC than serum UA (OR = 1.10). Gomori methenamine silver staining revealed in PSC an intense deposit of urates in the lens fibres in equatorial regions, and in subcapsular fibres in posterior regions of the lens. Such staining was not detected in the lens with non-PSC. Treatment with UA-induced senescence and apoptosis in human lens epithelial cells in a dose dependent manner. Our results suggest that the elevated level of UA in aqueous humour causes a deposition of urates in human lens epithelium, which could possibly lead to dysfunction of these cells that generates opacification in PSC. Conclusions and Relevance These findings indicate the local action of excessive UA in the pathogenesis of PSC. Control of serum UA level could delay the progression of PSC.