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

Bruce A. Berkowitz, Hongmei Luan, Rita R. Gupta, Daniel Pacheco, Andres Seidner, Robin Roberts, Jessica Liggett, Deborah L. Knoerzer, Jane R. Connor, Yunpeng Du, Timothy S. Kern, Yasuki Ito

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

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-Nos2tm1Lau 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.

Original languageEnglish
Pages (from-to)173-178
Number of pages6
JournalDiabetes
Volume53
Issue number1
DOIs
Publication statusPublished - 01-2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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