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

We aimed 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. In urethane anesthetized Sprague Dawley rats or C57BL/6 mice, functional magnetic resonance imaging 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 iNOS (n = 6). In addition, the retinal ΔPO₂ of the following mouse groups were compared: C57BL/6 mice (n = 20), C57BL/6-Nos2^tm1Lau mice (n = 10), 4-month diabetic mice (n = 13), and 4-month diabetic knockout mice (n = 6). Only the ΔPO ₂ of the superior hemiretina of the diabetic rat and mice groups were significantly subnormal (P < 0.05). The superior ΔPO₂ of the diabetic rats treated with the prodrug was not significantly (P > 0.05) different from their respective normal controls. In the mice experiments, the superior retinal ΔPO₂ of the iNOS null mice was not statistically different (P > 0.05) from that of normal control mice. iNOS is required for the development of an early subnormal ΔPO₂ in experimental diabetic retinopathy.