MODULATION OF GLUTAMATERGIC AND PURINERGIC PATHWAY IN PRIMARY NEURONAL CELLS OF RETINA IN DIABETIC MICE AND THEIR CONTROLS NOT DIABETICS: Study in vitro of possible antioxidant mechanisms in the neuroproteção of retina.

Abstract

The diabetic retinopathy (RD) is a chronic complication characterized by the degeneration of the neurons, glial cells and accompanied by extensive microvascular dysfunction in the retina. However, several biochemical evidences were described associates to the toxicity for hyperglycemia in retinal cells, among them oxidative stress. The oxidative stress was already described as pivotal in the neurodegenerative disease of the diabetic retina, especially for the generation of pro-oxidants, inflammatory mediators and toxic neurotransmitters. In the retina of rat diabetics and studies in vitro in culture of primary cells of retina it was show a significant increase experimentally in the production of reactive oxygen especies (ROS) for the mitochondrion, system NADPH-oxidase with activation of type NMDA receptors (glutamatergic) and synergism with purinergic P2X7 receptors. As models of culture in vitro of primary retinal cells constitute an appropriate model for us evaluate mechanisms neurodegenerative, we will analyze in primary culture of neural cells of the retina obtained of rat experimentally diabetics and their controls no-diabetics the production of ROS, expression of NMDA receptor and this modulation in the glutamate release, the expression of P2X7 receptor and this release of ATP vesicular compared with their controls no-diabetics respectively. To access the possible involved mechanisms, the cells will be submitted to different treatments with antioxidant/anti-inflammatory compounds and/or by small RNA interference (siRNA) for type NMDA and P2X7 receptors. The objective of this study is to profound the knowledge of the mechanisms physiopatogenic involved in neurodegenerative processes in the diabetes and to demonstrate possible neuroprotectors of antioxidant compounds in this context.