Abstract

Objective: Diabetic retinopathy (DR) displays the features of a neurodegenerative disease. Oxidative stress is involved in the pathogenesis of DR. This investigation sought to determine whether hypertension exacerbates oxidative stress, neurodegeneration and mitochondrial dysfunction that exists in DR and whether these changes could be minimized by the angiotensin II type 1 receptor blocker (ARB) losartan.

Research Design and Methods: Diabetes was induced in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The diabetic SHR groups were assigned to receive or not receive losartan.

Results: The level of apoptosis in the retina was higher in diabetic WKY rats (DM-WKY) than the control group, and higher levels were found in diabetic SHR (DM-SHR). The apoptotic cells expressed neural and glial markers. The retinal glial reaction was more evident in DM-WKY and was markedly accentuated in DM-SHR rats. Superoxide production in retinal tissue increased in DM-WKY and a greater increase occurred in DM-SHR rats. Glutathione levels decreased only in DM-SHR rats. As a consequence, the levels of nitrotyrosine and 8-hydroxy 2′-deoxyguanosine, markers of oxidative stress, were elevated in diabetic groups, mainly in DM-SHR rats. Mitochondrial integrity was dramatically affected in the diabetic groups. The ARB treatment reestablished all of the above-mentioned parameters.

Conclusions: These findings suggest that concomitance of hypertension and diabetes exacerbates oxidative stress, neurodegeneration and mitochondrial dysfunction in the retinal cells. These data provide the first evidence of AT₁ blockage as a neuroprotective treatment of diabetic retinopathy by reestablishing oxidative redox and the mitochondrial function.