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Click to add/remove this article to your list of 'My Favorites' A Role for 5-Lipoxygenase in Diabetic Retinopathy

Year: 2006

Abstract Number: 225-OR


Institutions: Cleveland, OH.

Results: Evidence suggests that diabetic retinopathy may result from chronic inflammation. Clinically, a hallmark lesion of diabetic retinopathy is degeneration of retinal capillaries, which eventually progresses to retinal ischemia and subsequent neovascularization. These degenerate capillaries (acellular capillaries) can be studied and quantified histologically. The role of eicosanoids as inflammatory mediators in the development of diabetic retinopathy is explored using the mouse model. Diabetes was induced with streptozotocin in C57Bl/6 mice (wildtype and 5-lipoxygenase-/-) and acellular capillaries quantified after 9 months of diabetes. As expected, diabetes caused a significant increase in the number of degenerate retinal capillaries in wildtype animals, whereas 5-lipoxygenase-/- diabetic mice were protected from the capillary degeneration (p=0.01). A current hypothesis proposes that the formation of acellular capillaries is due to early obstruction of the retinal microvasculature by white blood cells. Diabetic wild-type mice have an increased adhesion of leukocytes (i.e., leukostasis) in comparison to nondiabetic wild-type mice (15.5 ± 7.0 leukocytes/retina vs. 3 ± 1.9 leukocytes/retina, respectively, p<0.005), whereas the diabetes-induced leukostasis is absent in diabetic 5-lipoxygenase-/-mice. This data suggests that the eicosanoids produced by 5-lipoxygenase in the mouse participate in the pathogenesis of diabetic retinopathy, and that inhibition of this lipoxygenase might offer a novel therapeutic target to inhibit development of the retinopathy.