Inhibition of lens opacification in x-irradiated rats treated with WR-77913

Radiation induced cataracts are models for studying mechanisms of lens opacification. WR-77913, S-3-(amino-2-hydroxypropyl) phosphorothioate (NCS-318809), has been identified as a radioprotective agent. Injection of WR-77913 (1160 mg/kg, i.p.) 15 to 30 min before exposure to 15.3 gray of x-irradiation inhibited rat lenses from developing radiation cataracts. Irradiated rats which did not receive the drug developed dense cataracts. Lenses from control rats which received no radiation remained transparent. Individual lenses were weighed, homogenized, and assayed for protein content using the Lowry method. The molecular weight distribution of soluble protein was determined by HPLC. Mean lens weights were: controls 48.2 mg; irradiated, drug-treated 45.9 mg; and irradiated, nontreated 45.5 mg. Protein accounted for over 40% of the lens weight in control and drug-treated rats and less than 20% for the nontreated cataractous lenses. Water was less than 60% of the lens weight in control and drug-treated rats and over 80% in cataractous lenses. Insoluble protein ranged from 12 to 17% of the total lens weight for each group. The ratio of insoluble to soluble lens protein was 0.40 for control, 0.65 for drug-treated, and 11.28 for cataractous rat lenses. HPLC confirmed a dramatic loss of soluble protein and a complete absence of protein below 25K daltons in cataractous lenses. Proteins below 25K daltons accounted for over 25% of the soluble protein in control and drug-treated rat lenses. WR-77913 stabilizes protein composition and appears to be an effective inhibitor of radiation cataractogenesis.