Oral administration of a xanthine oxidoreductase inhibitor suppresses retinal degeneration and preserves ocular ATP levels

Retinal degeneration results in irreversible visual impairment. In a neurodegenerative animal model, xanthine oxidoreductase inhibitor application reduced disease severity. The present study examined the effect of a novel xanthine oxidoreductase (XOR) inhibitor, NC-2500, on a spontaneous retinal degeneration rat model via oral administration. Three-and-a half-week-old RCS (-/-) rats received formulated NC-2500 orally daily for 19 days, and 2-week-old RCS (+/+) rats received it for 21 days. Retinal damage was evaluated histologically. The purine metabolites were analyzed using high-performance liquid chromatography. An electroretinogram was performed on RCS (+/+) rats on the 17th day of treatment. The RCS (-/-) showed rapid, and the RCS (+/+) showed slow progression in retinal degeneration. The thinning of the outer nuclear layer and photoreceptor layer was reduced by NC-2500 administration for RCS (-/-). The adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels in eyes were elevated in the NC-2500 group. The electroretinogram test for RCS (+/+) revealed a greater response in the NC-2500 treated group than in the control group under light-adapted conditions. The levels of hypoxanthine and xanthine in the eyes were higher in the NC-2500 group. These results indicate that the oral administration of xanthine oxidoreductase inhibitor suppressed the progression of spontaneous retinal degeneration and was associated with preservation of ATP levels in the eyes.