α-Tocopherol Reduces Diabetes-Induced Retinal Vascular Leakage and ERG Abnormalities in the Rat
Abstract Number: 2153-PO
Authors: KIM M. DELLA VECCHIA, NIGEL TIMOTHY, ALLEN C. CLERMONT, SUSAN L. ROOK, GEORGE L. KING, LLOYD P. AIELLO, SVEN-ERIK BURSELL
Institutions: Boston, MA
Results: Mediators of diabetic retinal vascular abnormalities include activation of the diacylglycerol (DAG)/protein kinase C (PKC) pathway, and generation of reactive oxygen intermediates (ROI). The anti-oxidant, α-tocopherol (Vitamin E) inhibits PKC by enhancing DAG kinase activity. This study shows that Vitamin E ameliorates the diabetes-induced impairment in retinal vascular permeability (RVP) and electroretinogram (ERG) and reduces apoptosis. Sprague-Dawley non-diabetic (NDM) and STZ-induced diabetic (DM) rats were treated with 40 mg/kg α-tocopherol or placebo QOD from onset of diabetes for 4 weeks. We measured plasma hydroperoxide levels, single flash ERGs (flash time 5 ms, illumination 14000 cd/m², 1 hour dark adaptation, to evaluate a- and b-wave and oscillatory potential (OP) characteristics), and RVP (Evans-blue albumin permeation). Separately, retinal apoptosis was examined from retinal sections. Plasma hydroperoxide increased 2.4 fold in DM (20.6±9.5 μmol/l, n=7) versus NDM (4.9±4.1 μmol/l, p<0.05) and was normalized by Vitamin E treatment in DM (3.7±3.7 μmol/l, n=7, p<0.05). Peak latency was prolonged (p<0.05) in DM for OP1-4, b-wave, and summation of OP1-4 as compared to NDM. Vitamin E treatment of DM inhibited these diabetes-induced changes in peak OP2 latency and summed OP1-4 by 44±32% (p=0.025) and 36±41% (p=0.046) respectively as compared to DM control. ERG amplitude was reduced (p<0.05) in DM for a-wave, OP1-3, b-wave, and summed OP1-4 compared to NDM. Diabetes-induced amplitude alterations for OP1, OP2, & b-wave decreased 85±77% (p=0.006), 40±45% (p=0.041), and 57±50% (p=0.036) by Vitamin E treatment as compared to DM control. Retinal vascular leakage increased by 94±61% (n=4) in DM compared to NDM, an effect abolished by Vitamin E treatment compared to untreated DM (n=4, 6.3±2.1 vs 22.7±7.2, p=0.006). α-Tocopherol treatment ameliorates diabetes-induced ERG and RVP abnormalities. High-dose Vitamin E may have a therapeutic role in treating diabetic ocular disease.