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 (Delta PO(2)) during a carbogen-inhalation challenge. In the rat experiments, the retinal Delta PO(2) 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 Delta PO(2) of the following mouse groups were compared: C57BL/6 mice (n = 20), C57BL/6-Nos2(tm1 Lau) mice (n = 10), 4-month diabetic mice (n = 13), and 4-month diabetic knockout mice (n = 6). Only the Delta PO(2) of the superior hemiretina of the diabetic rat and mice groups were significantly subnormal (P < 0.05). The superior Delta PO(2) 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 Delta PO(2) 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 Delta PO(2) in experimental diabetic retinopathy.
Berkowitz
Bruce A
BA
Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan 48201, USA. baberko@med.wayne.edu
Luan
Hongmei
H
Gupta
Rita R
RR
Pacheco
Daniel
D
Seidner
Andres
A
Roberts
Robin
R
Liggett
Jessica
J
Knoerzer
Deborah L
DL
Connor
Jane R
JR
Du
Yunpeng
Y
Kern
Timothy S
TS
Ito
Yasuki
Y
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000503:physiopathology*; D004195:Disease Models, Animal; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D009900:Optic Nerve / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000502:physiology*; D010313:Partial Pressure; D051381:Rats; D012160:Retina / Q000503:physiopathology*
D001786:Blood Glucose; D002245:Carbon Dioxide; D009569:Nitric Oxide; D010100:Oxygen