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M. A. Al-Shabrawey, II, R. Mussell, G. I. Liou, S. K. Akeel, A. M. Tawfik; Diabetes Increases 12-Lipoxygenase Expression in Human and Mouse Retinas. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5370.
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Diabetic retinopathy is a vision threatening complication of diabetes associated with vascular damage and retinal cell apoptosis. 12- hydroxyeicosatetraenoic acid (12-HETE) is a biologically active metabolite of arachidonic acid produced by 12-lipoxygenase enzyme (12-LO). 12- HETE has been shown to induce leukocyte/endothelial interaction and neuronal cell death, both are major processes involved in the pathogenesis of diabetic retinopathy. However, the specific role of 12-HETE in diabetic retinopathy has not yet been elucidated. So, the goal of this study was to investigate the changes in the expression and activity of 12-LO in diabetic retina and correlating these changes with the vascular and neuronal cell injury associated with diabetic retinopathy.
Expression of 12-LO and the inflammatory marker, intracellular adhesion molecule-1 (ICAM-1) was examined in retinas from human and streptozotocin-induced diabetic mice using Western blotting and immunofluroscence techniques. One group of diabetic mice was treated with 12-LO inhibitor baicalein (20mg/kg) for 12 weeks. Apoptotic cells in the retina were quantified using terminal dUTP nick-end labeling (TUNEL). We also tested the effect of baicalein on lipopolysacchardies (LPS)-induced ICAM-1 expression to evaluate the role of 12-LO in retinal inflammation.
Diabetes increased 12-LO expression in human and mouse retinas (2 and 1.5 fold respectively). This was associated with a marked increase in the level of ICAM-1 and number of apoptotic cells. Immunoflurosence showed that 12-LO expression was localized mainly in retinal vessels and related glial cells. Inhibition of 12-LO by baicalein treatment reduced the number of apoptotic cells and ICAM-1expression in diabetic and LPS injected mice.
12-LO plays a role in vascular and neuronal injury associated with diabetic retinopathy. Inhibition of 12-LO activity could be a new therapeutic strategy to treat diabetic retinopathy.
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