Retinal Oxidative Stress Induced by High Intraocular Pressure

Abstract

Abstract: : Purpose: The aim of the present study was to examine the status of the endogenous antioxidant defense system in retinas of rats with chronic intraocular hypertension induced by the intracameral injection of hyaluronic acid (HA). Methods: HA (1% in saline) was injected weekly in the anterior chamber of male Wistar rats, whereas the contralateral eye was injected with vehicle. Intraocular pressure (IOP) was assessed with a TonoPen XL. Rats were sacrificed after 3 or 6 weeks of ocular hypertension, and the retinas were dissected. Catalase and glutathione peroxidase activities, as well as the levels of reduced glutathione were measured by standard spectrophotometric methods. Thiobarbituric acid reactive substances (TBARS) levels were measured as an index of lipid peroxidation. Nitric oxide synthase (NOS) activity was determined through the conversion of ³H-L-arginine to ³H-L-citrulline, while retinal melatonin content was quantified by radioimmunoassay. Heme oxygenase (HO) levels were assessed by western blotting. Results: Retinal catalase activity was significantly decreased after 3 and 6 weeks of ocular hypertension. Only after 6 weeks, an increase in TBARS levels and a decrease in reduced glutathione levels were observed. Glutathione peroxidase activity increased after 3 weeks and decreased after 6 weeks in HA-injected eyes as compared to vehicle- injected eyes. A decrease in NOS activity and an increase in HO-1 levels were only evident after 6 weeks of ocular hypertension. Retinal melatonin content was significantly lower in the retinas of HA-treated eyes for 3 weeks. Conclusions: These results indicate that the retinal activity of the endogenous antioxidant defense system is affected by ocular hypertension. Since some of these changes preceded functional and histologycal damage induced by the chronic injection of HA, present results support a causal relationship between both phenomena. Moreover, based on the multiple evidence in favor of a role for melatonin as an endogenous antioxidant, it seems likely that some of the changes in the antioxidant response may be associated to a decrease in retinal levels of this methoxyindole

Keywords: melatonin • pathology: experimental • oxidation/oxidative or free radical damage