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F. J. Romero, S. Johnsen-Soriano, M. Sancho-Tello, M. Garcia-Pous, S. Garcia-Delpech, E. Arnal, M. Miranda, M. Diaz-Llopis, F. Bosch-Morell; Early Lipoic Acid Intake Protects Retina in Diabetic Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5920.
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The aim of this study was to confirm biochemical and functional changes in retina after a short diabetic insult and to test the effect of lipoic acid treatment on those parameters.
The investigation conformed with ARVO Statement for the Use of Animals in Ophthalmic and Vision Research and Declaration of Helsinki. Diabetes was induced by a single subcutaneous injection of 200 mg alloxan/kg body weight (66 mg/ml) in 0.1 M citrate buffer, pH 4.5 and the control group received a subcutaneous injection of citrate buffer alone. Mice were considered diabetic with a blood glucose level higher than 16 mM, 4 days after alloxan treatment. Then, animals were divided into subgroups (control, control+lipoic acid, diabetic, diabetic+lipoic acid, diabetic+insulin, diabetic+insulin+lipoic acid) and maintained with their respective treatment for 3 weeks. At least 20 animals were used in each group. Lipoic acid (Sigma, St. Louis, MO, USA) was administered ip daily at a dose of 100 mg/kg body weight, and insulin at 500 mU/g body weight. Blood samples were taken daily from the tail vein to assay blood glucose levels. Glutathione (GSH) and Malondialdehyde (MDA) concentrations in addition to glutathione peroxidase activity (GPx activity) were measured in eye homogenates without lens as oxidative stress markers. The last day of the experiment electroretinograms (ERG) were recorded, and b-wave amplitudes were measured.
Early administration of lipoic acid prevented the statistically significant decrease of the antioxidant enxymes GSH and GPx activity and increase in MDA content observed in the retina of diabetic animals. Moreover, when functionality of the retina was tested in form of electroretinogram recordings, lipoic acid restored b-wave amplitude in diabetic animals to control values. In agreement with previous findings by other authors, no statistical significant increase in the number of TUNEL+ cells was found, though a slight increase was observed after this short diabetic insult.
Lipoic acid has an protective effect by slowing the onset and progression of retinopathy, but must be administered as early as possible to the diabetic patients in order to prevent oxidative damage and its consequences such as apoptosis and possible vision loss.
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