Diabetic retinopathy is a severe retinal complication that diabetic patients are susceptible to present. Although this disease is currently characterized as a microvascular disease, there is growing evidence that neural changes occur and maybe precede vascular impairments. Using chicken retina, an avascular tissue with no direct contact with blood vessels and neural retina, this study aimed to evaluate the influence of acute exposure to high glucose concentration in the retinal GABAergic system, and the role of nitric oxide (NO) in this modulation. Therefore, in ex vivo experiments, retinas were incubated in control (10 mM glucose) or high glucose condition (35 mM) for 30 min. By using DAF-FM to evaluate NO production, it was possible to show that high glucose (HG) significantly increased NO levels in the outer nuclear layer, inner nuclear layer (outer and inner portion), and inner plexiform layer. It was also observed that HG increased GABA immunoreactivity (IR) in amacrine and horizontal cells. HG did not change glutamic acid decarboxylase-IR, whereas it decreased GABA Transporter (GAT) 1-IR and increased GAT-3-IR. The co-treatment with 7-NI, an inhibitor of neuronal nitric oxide synthase (nNOS), blocked all changes stimulated by HG exposure. The concomitant exposure with SNAP-5114, a GAT-2/3 inhibitor, blocked the increase in GABA-IR caused by HG incubation. Therefore, our data suggest that hyperglycemia induces GABA accumulation in the cytosol by modulating GABA transporters. This response is dependent on NO production and signaling.
Keywords: Avascular; Diabetes; Diabetic retinopathy; GABA; Neuronal nitric oxide synthase; Retina.
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