Abstract
BackgroundDiabetic retinopathy is a major complication of dysregulated hyperglycemia. Retinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy. Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by docosahexaenoic acid (DHA, 22:6 ω-3) and eicosapentaenoic acid (EPA, 20:5 ω-3). The influence of dietary omega-3 PUFA on brain zinc metabolism has been previously implied. Zn2+ is essential for the activity of Δ6 desaturase as a co-factor that, in turn, converts essential fatty acids to their respective long chain metabolites. Whether essential fatty acids (EFAs) α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood.MethodsRF/6A cells were treated with different concentrations of high glucose, α-linolenic acid and linoleic acid and Zn2+. The alterations in mitochondrial succinate dehydrogenase enzyme activity, cell membrane fluidity, reactive oxygen species generation, SOD enzyme and vascular endothelial growth factor (VEGF) secretion were evaluated.ResultsStudies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by both linoleic acid (LA) and α-linolenic acid (ALA), while the saturated fatty acid, palmitic acid was ineffective. A dose–response study with ALA showed that the activity of the mitochondrial succinate dehydrogenase enzyme was suppressed at all concentrations of glucose tested to a significant degree. High glucose enhanced fluorescence polarization and microviscocity reverted to normal by treatment with Zn2+ and ALA. ALA was more potent that Zn2+. Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity. ALA suppressed ROS generation to a significant degree in a dose dependent fashion and raised SOD activity significantly. ALA suppressed high-glucose-induced VEGF secretion by RF/6A cells.ConclusionsThese results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage.
Highlights
IntroductionRetinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy
Diabetic retinopathy is a major complication of dysregulated hyperglycemia
Hyperglycemia induces an increase in protein kinase C activity in cultured bovine retinal capillary endothelial cells that could enhance neovascularization and cell growth that leads to the development of diabetic vascular complications [4]
Summary
Retinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy. Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by docosahexaenoic acid (DHA, 22:6 ω-3) and eicosapentaenoic acid (EPA, 20:5 ω-3). High blood glucose levels in diabetic patients increase the risk of diabetic microangiopathy. High glucose levels are capable of altering homeostasis of vascular endothelial cells and lead to changes in gene expression that might initiate diabetic retinopathy [1]. Exposure of retinal endothelial cells to high glucose promotes a promigratory phenotype that contributes to the development of diabetic retinopathy. Hyperglycemia induces an increase in protein kinase C activity in cultured bovine retinal capillary endothelial cells that could enhance neovascularization and cell growth that leads to the development of diabetic vascular complications [4]
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