LIGHT-DEPENDENT CORNEAL TOXICITY IN STREPTOZOCIN-TREATED RATS

Purpose. To find the role of nitric oxide (NO) in streptozocin-induced corneal toxicity in rats. Methods. Spraque-Dawley rats were injected intraperitoneally with streptozotocin (65 mg/kg). For exposure to ligh t, each rat cage was placed in a box surrounded with aluminum foil and illuminated for 6 hours per day with two 20-W fluorescent lamps at a distance of 50 cm. When not exposed to light, each cage was placed in a dark room. Some animals with and without light exposure also were tr eated with and without streptozotocin treatment. Control animals did n ot receive streptozotocin and were housed in a darkroom 24 hours a day . Each group contained 15 rats. After 1, 3, 7, and 10 days of light ex posure, concentrations of nitrite and nitrate, stable oxidation produc ts of NO, were measured in the aqueous humor. Corneal changes also wer e examined by electron microscopy after 10 days. To examine specific N O-induced histopathologic changes, several rats were injected subconju nctivally with a balanced saline solution containing the NO-generating agent (S-nitroso-N-acetyl-D,L-penicillamine or minoethyl)-N-(2-ammoni oethyl)amino]diazen-1-ium-1, 2-diolate]). Results. Concentrations of n itrite and nitrate were highest in the streptozocin-injected rats irra diated while under the fluorescent lamp. On the 10th day of the strept ozotocin injection, the concentrations of nitrite and nitrate in strep tozocin-treated rats irradiated while under the fluorescent lamp was a lmost two-and-a-half times greater than that of nontreated rats reared in the dark (111.37 +/- 7.47 mu M, 45.43 +/- 3.91 mu M, respectively) . Slit-lamp biomicroscopy showed that the corneas swelled gradually an d opacified by the third day in the irradiated streptozocin-injected g roup. The corneas became hazy to the point of indistinguishable detail structures by the 10th day, although those of the other rats were rel atively clear at the same time. Histopathologically, ultrastructural c hanges included the remarkable swelling of intracytoplasmic organelles , including mitochondria, and denaturation of collagen fibril was show n in the streptozocin-injected-irradiated rats by the 10th day. The co rneas injected with two NO-generating agents, S-nitroso-N-acetyl-D,L-p enicillamine and (Z)-1-[2-(2-aminoethyl)-N-(2- ammonioethyl) amino]dia zen-1-ium-1, 2-diolate, showed similar but more severe changes. Conclu sions, Nitric oxide can cause damage to the mitochondria, the most imp ortant energy source of the cell, and induce ultrastructural damage to the corneal endothelium and fibroblast. The authors suggest that NO i s associated with the development of corneal cytotoxicity and that NO production and subsequent cytotoxicity call be prevented by blocking t o photoactivation.