Aquaporin Changes during Diabetic Retinopathy in Rats Are Accelerated by Systemic Hypertension and Are Linked to the Renin-Angiotensin System

PURPOSE. We explored the relationship between the renin-angiotensin system (RAS) and aquaporins (AQP1 and AQP4 in Muller glia and astrocytes) in diabetic retinopathy (DR) with and without systemic hypertension. METHODS. Diabetes was induced in spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats by intraperitoneal injections of streptozotocin. The diabetic and control non-diabetic rats were assigned randomly to receive no anti-hypertension treatment, or to be treated with the angiotensin II receptor blocker (ARB), valsartan (40 mg/kg/d) or the beta-blocker, metoprolol (50 mg/kg/day). Eight weeks later, retinas were evaluated by immunohistochemistry and Western blot to detect changes in the expression of AQP1, AQP4, and glial fibrillary acidic protein (GFAP). RESULTS. Hypertension increased expression of glial GFAP and AQP4 (P < 0.01), but not AQP1 (P > 0.05) in diabetic rats. Valsartan and metoprolol decreased GFAP, AQP1, and AQP4 expression in diabetic SHR rats (P < 0.01). Valsartan decreased GFAP and AQP1 expression in diabetic WKY rats (P < 0.01), while metoprolol did not. CONCLUSIONS. Activation of Muller glia and astrocytes was involved in the mechanism by which systemic hypertension affects DR. AQPs and macroglia were linked to changes in the RAS in DR. Changes in aquaporin expression in DR were increased by hypertension. This provides additional support for the early use of an ARB in the treatment of DR, especially in cases with retinal edema. (Invest Ophthalmol Vis Sci. 2012;53:3047-3053) DOI:10.1167/iovs.11-9154