Regulation of the Early Subnormal Retinal Oxygenation Response in Experimental Diabetes by Inducible Nitric Oxide Synthase
- Bruce A. Berkowitz12,
- Hongmei Luan1,
- Rita R. Gupta1,
- Daniel Pacheco1,
- Andres Seidner1,
- Robin Roberts1,
- Jessica Liggett1,
- Deborah L. Knoerzer3,
- Jane R. Connor3,
- Yunpeng Du4,
- Timothy S. Kern4 and
- Yasuki Ito1
- 1Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan
- 2Department of Ophthalmology, Wayne State University, Detroit, Michigan
- 3Pharmacia Corporation, St. Louis, Missouri
- 4Department of Medicine, Case Western Reserve University, Cleveland, Ohio
- Address correspondence and reprint requests to Bruce A. Berkowitz, PhD, Department of Anatomy and Cell Biology, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201. E-mail: baberko{at}med.wayne.edu
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 ΔPO2 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.
- AMG, aminoguanidine
- iNOS, inducible nitric oxide synthase
- MRI, magnetic resonance imaging
- NO, nitric oxide
- NOS, NO synthase
Footnotes
-
B.A.B. has received honoraria and research support from Pharmacia Corporation.
-
- Accepted October 3, 2003.
- Received October 21, 2002.
- DIABETES
