Can metformin modulate the retinal degenerative changes in a rat model of retinitis pigmentosa?

Retinitis pigmentosa (RP) affects over a million people worldwide, characterized by photoreceptor cell death, progressive retinal degeneration, and visual loss. Metformin is demonstrated as a potential therapeutic approach for preventing light-induced retinal degeneration by decreasing apoptosis and oxidative stress. This work aimed to investigate the effect of metformin on the retina of the N-Ethyl-N-nitrosourea (ENU) induced rat model of RP. Eighteen adult male Wistar rats were divided into two groups. Group I: normal vehicle control (N = 6). Group II: ENU-induced photoreceptor degeneration (N = 12) received a single intraperitoneal injection of ENU at a 600 mg/kg dose. Rats in group II were equally divided into two subgroups: IIa: photoreceptor degeneration-induced group and IIb: metformin-treated group (200 mg/kg) for seven days. Specimens from the retina were processed for light and electron microscopy. In ENU treated group, the retina revealed vacuolations and morphological changes in the glia (Müller cells and microglia) and blood capillaries. Increasing caspase-3 (apoptotic marker), iNOS (oxidative stress marker), CD68 (macrophage marker) and glial fibrillary acidic protein (GFAP) expression were detected. In the metformin-treated group, the retinal vacuolations reduced with the morphological improvement in the glia and blood capillaries. Caspase-3, iNOS, CD68, and GFAP expression decreased. Metformin was found to have a neuroprotective effect on the retina in ENU induced rat model of RP.

Metformin treatment confers protection of the optic nerve following photoreceptor degeneration.

Acquired or inherited or photoreceptor loss causes retinal ganglion cell loss and ultimately axonal transport alteration. Thus, therapies should be applied early during photoreceptors degeneration before the remodeling process reaches the inner retina. This study aimed to evaluate the protective effect of metformin on the rat optic nerve following photoreceptors loss induced by N-Ethyl-N-nitrosourea (ENU). Eighteen adults male Wistar rats were divided into two groups. Group I: normal vehicle control (n=6). Group II: ENU-induced photoreceptors degeneration (n=12) received a single intraperitoneal injection of ENU at a dose of 600 mg/kg. Rats in group II were equally divided into two subgroups: IIa: photoreceptor degeneration induced group and IIb: metformin treated group (200 mg/kg) for 7 days. Specimens from the optic nerve were processed for light and electron microscopy. In ENU treated group, the optic nerve revealed reduction in the diameter of the optic nerve fibers and thinning of myelin sheath with morphological changes in the glia (astrocytes, oligodendrocytes, and microglia). Caspase-3 (apoptotic marker), iNOS (oxidative stress marker) and CD68 (macrophage marker) expression increased. In metformin-treated group, the diameter of optic nerve fibers and myelin sheath thickness increased with improvement of the deterioration in the glia. Caspase-3, iNOS and CD68 expression decreased. Metformin ameliorates the histological changes of the rat optic nerve following photoreceptors loss induced by ENU.