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Experimental Diabetes Research
Volume 2007 (2007), Article ID 21976, 7 pages
Research Article

Metabolic Memory Phenomenon and Accumulation of Peroxynitrite in Retinal Capillaries

Kresge Eye Institute, Wayne State University, Detroit, MI 48201, USA

Received 26 February 2007; Accepted 17 April 2007

Academic Editor: Subrata Chakrabarti

Copyright © 2007 Renu A. Kowluru et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Aim. Diabetic retinopathy resists reversal after good glycemic control (GC) is reinitiated, and preexisting damage at the time of intervention is considered as the major factor in determining the outcome of the GC. This study is to investigate the role of peroxynitrite accumulation in the retinal capillaries in the failure of retinopathy to reverse after reestablishment of GC, and to determine the effect of this reversal on the activity of the enzyme responsible for scavenging mitochondrial superoxide, MnSOD. Methods. In streptozotocin-diabetic rats, 6 months of poor glycemic control (PC, glycated hemoglobin, GHb>12.0%) was followed by 6 additional months of GC (GHb about 6%). The trypsin-digested retinal microvessels were prepared for immunostaining of nitrotyrosine (a measure of peroxynitrite) and for counting the number of acellular capillaries (a measure of histopathology). The retina from the other eye was used to quantify nitrotyrosine concentration, MnSOD activity and the total antioxidant capacity. Results. Reversal of hyperglycemia after 6 months of PC had no significant effect on nitrotyrosine concentration in the retina, on the nitrotyrosine-positive retinal capillary cells and on the number of acellular capillaries; the values were similar in PC-GC and PC groups. In the same rats retinal MnSOD activity remained inhibited and the total antioxidant capacity was subnormal 6 months after cessation of PC. Conclusions. Peroxynitrite accumulation in the retinal microvasculature, the site of histopathology, fails to normalize after reversal of hyperglycemia, and superoxide remains inadequately scavenged. This failure of reversal of peroxynitrite accumulation could be, in part, responsible for the resistance of diabetic retinopathy to reverse after termination of PC.