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Change in levels of vascular endothelial growth factors (VEGF) isoforms is a feature of diabetic retinopathy. To better characterize the expression of VEGFa and VEGF165b isoforms in the diabetic retina and to explore how oxidative stress influences the balance between these molecules, we have used the Ins2Akita mouse model of diabetes. Retinal tissue collected from wild-type and Ins2Akita mice, together with D407 retinal pigment epithelial (RPE) cells were used as experimental models. The retina of the Ins2Akita diabetic mice was shown to have decreased levels of the anti-angiogenic VEGF165b protein and a high production of reactive oxygen species (ROS). High glucose deregulated the expression of VEGF proteins as well as the production of ROS in RPE cells. Physiological levels of H2O2 were found to preserve the equilibrium between VEGF isoforms in RPE cells while pathological levels down-regulated the VEGF165b. Besides hyperglycemia, oxidative stress also contributes to disrupt the equilibrium between proand anti-angiogenic factors in the retina, a profile frequently found in retinal pathologies. Abbreviations: AMD – age-related macular degeneration; BRB – blood-retinal barrier; DR – diabetic retinopathy; PEDF – pigment epithelium-derived; factor RPE – retinal pigment epithelial; ROS – reactive oxygen species; VEGF – vascular endothelial growth factor

Oxidative stress modulates the expression of VEGF isoforms in the diabetic retina