Add time:08/07/2019         Source:sciencedirect.com

Pregabalin is the first drug to receive FDA approval for treating diabetic neuropathic pain. This study investigated the neuroprotective effect of pregabalin in an experimental model of diabetic retinopathy and tested some possible mechanisms underlying the putative neuroprotective effect. Male Wistar rats received streptozotocin (45 mg/kg) to induce type 1 diabetes mellitus. After two weeks, a course of pregabalin (3, 10 and 30 mg/kg) has been launched for five consecutive weeks. Retinal expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) was estimated by real-time PCR and retinal glutamate content was also estimated. Further, retinal caspase-3 immunoblotting and DNA fragmentation assays determined the degree of apoptosis. Pregabalin improved histopathological abnormalities in diabetic retinas and suppressed the diabetes-enhanced retinal expression of IL-1β, TNF-α, CD11b (a surface marker for microglia) while attenuated expression of caspase-3 and DNA fragmentation versus the diabetic group. In addition, diabetic rats treated with pregabalin displayed reductions in retinal glutamate, nitric oxide and malondialdehyde (MDA) and enhanced reduced glutathione (GSH) content versus the diabetic controls. Furthermore, pregabalin enhanced the histopathological picture and reduced fibrosis in the optic nerve of diabetic rats in addition to suppression of the content of the glia fibrillary acidic protein. The findings provide the first evidence demonstrating that pregabalin alleviates retinal neuroinflammation, apoptosis and oxidative stress in an experimental type 1 diabetes mellitus. Therefore, pregabalin might serve as a potential therapy for retinopathy after adequate clinical research.

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