5-Lipoxygenase, but Not 12/15-Lipoxygenase, Contributes to Degeneration of Retinal Capillaries in a Mouse Model of Diabetic Retinopathy

Abstract Objective: Lipoxygenases are regulators of chronic inflammation and oxidative stress generation. We evaluated the role of 5- and 12-lipoxygenases in the development of diabetic retinopathy. Research design and methods: Wild-type (WT) mice, 5-lipoxygenase-deficient (5-LO) mice, and 12/15-lipoxygenase-deficient (12-LO) mice were assessed 1) after 9 months of diabetes for retinal histopathology and leukotriene receptor expression, and 2) after 3 months of diabetes for leukostasis and retinal superoxide generation. Results: Diabetic WT mice developed the expected degeneration of retinal capillaries and pericytes, and increases in both leukostasis and superoxide production (P diabetic wt mice were enriched with receptors for the 5-lo metabolite leukotriene b 4 . Conclusions: Diabetes-induced histological and biochemical alterations were significantly reduced in 5-LO-deficient mice, but not 12-LO-deficient mice. 5-LO represents a novel pathway for therapeutic intervention of diabetic retinopathy.