Effect of essential fatty acids on glucose-induced cytotoxicity to retinal vascular endothelial cells.
BACKGROUND
Diabetic 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.


METHODS
RF/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.


RESULTS
Studies 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.


CONCLUSIONS
These results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage.
Laboratory of Clinical Visual Science, Tongji Eye institute, Tongji University School of Medicine, Shanghai, China.
Junhui
J
Shen
Shengrong
S
Shen
Undurti N
UN
Das
Guotong
G
Xu
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000502:physiology / Q000633:toxicity*; D019787:Linoleic Acid / Q000494:pharmacology*; D008253:Macaca mulatta; D008560:Membrane Fluidity / Q000187:drug effects; D018384:Oxidative Stress; D019308:Palmitic Acid / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012171:Retinal Vessels / Q000473:pathology*; D055571:Secretory Pathway / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014783:Viscosity / Q000187:drug effects; D017962:alpha-Linolenic Acid / Q000494:pharmacology*
D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D017962:alpha-Linolenic Acid; D019308:Palmitic Acid; D019787:Linoleic Acid; D013482:Superoxide Dismutase; D005947:Glucose