Abstract
Abstract: :
Purpose: Administration of a cycloxygenase–2 (COX–2) inhibitor or an inhibitor of the inducible isoform of nitric oxide synthase (iNOS) during the first 3 mo of diabetes in rats prevents the development of subnormal retinal oxygenation response (ΔPO2). In this study, we tested the hypothesis that interventional treatment with either COX–2 or iNOS inhibitors, initiated after a subnormal retinal ΔPO2 has developed, will restore the retinal oxygenation response to normal. Methods: In urethane anesthetized Sprague Dawley rats, functional MRI was used to noninvasively measure ΔPO2 during a carbogen inhalation challenge. The following groups were compared: non–diabetic control (C, n = 5), untreated 4 mo diabetic (D, n = 6), diabetic rats untreated for the first 3 mo and for the last month treated orally with either L–N(6)–(1–iminoethyl)lysine 5–tetrazole amide, a prodrug of an inhibitor of iNOS (D+iNOSi, n = 6)) or an inhibitor of COX–2 (Celecoxib, D+COX2i, n = 7) animals. Results: As expected, there were no statistical differences (P > 0.05) between inferior hemiretinal ΔPO2 between any of the groups. As in previous studies, the superior hemiretinal response for group D was significantly lower than that in group C (P < 0.05). Superior hemiretinal ΔPO2 was normal (P < 0.05) for the D+COX2i group but subnormal (P < 0.05) for the D+iNOSi groups. Conclusions: COX–2 and iNOS, both of which appear to be important in the pathogenesis of diabetic retinopathy, initially contribute to subnormal oxygenation responses in diabetes, but during a later more chronic period of diabetes the effects of COX–2 and iNOS activity on ΔPO2 appear to dissociate. Functional MRI is useful for examining biochemical changes involved in the reversible and irreversible phases of the diabetic retinopathy.
Keywords: diabetic retinopathy • inflammation • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)