Regulation of the Early Subnormal Retinal Oxygenation Response in Experimental Diabetes by Inducible Nitric Oxide Synthase

Abstract

Abstract: : Purpose: To test the hypothesis that the inducible form of nitric oxide synthase (iNOS) contributes to the development of an early subnormal retinal oxygenation response in preclinical models of diabetic retinopathy. Methods: In urethane anesthetized Sprague Dawley rats or C57BL/6 mice, fMRI was used to noninvasively measure the change in retinal oxygen tension (ΔPO₂) during a carbogen inhalation challenge. In the rat experiments, the retinal ΔPO₂ of the following groups were compared: control rats (n = 9), 3 month diabetic rats (n = 5), and 3 month diabetic rats treated orally with L-N(6)-(1-iminoethyl)lysine 5-tetrazole amide, a prodrug of an inhibitor of inducible nitric oxide synthase (n = 6). In addition, the retinal ΔPO₂ of the following mouse groups were compared: C57BL/6 mice (20), C57BL/6-Nos2^tm1Lau mice (n = 10), 4 month diabetic mice (n = 13), and 4 month diabetic KO mice (n = 6). Results: The superior ΔPO₂ of diabetic rats treated with the prodrug was not significantly (P > 0.05) different from their respective normal controls. In the mouse experiments, the superior retinal ΔPO₂ of iNOS null mice was not statistically different (P > 0.05) from that of normal control mice. Only the ΔPO₂ of the superior hemiretina of diabetic rat and mouse groups were significantly (P < 0.05) subnormal. Conclusions: iNOS is required for the development of an early subnormal ΔPO₂ in experimental diabetic retinopathy.

Keywords: nitric oxide • diabetic retinopathy • imaging methods (CT, FA, ICG, MRI, OCT, RTA, S