Melatonin: a novel neuroprotectant for the treatment of glaucoma

Abstract

Glaucoma is a leading cause of blindness. Although ocular hypertension is the most important risk factor, several concomitant factors such as elevation of glutamate and decrease in gamma-aminobutyric acid (GABA) levels, disorganized NO metabolism, and oxidative damage could significantly contribute to the neurodegeneration. The aim of this report was to analyze the effect of melatonin on retinal glutamate clearance, GABA concentrations, NO synthesis, and retinal redox status, as well as on functional and histological alterations provoked by chronic ocular hypertension induced by intracameral injections of hyaluronic acid (HA) in the rat eye. In normal retinas, melatonin increased glutamate uptake, glutamine synthase activity, GABA turnover rate, glutamic acid decarboxylase activity, superoxide dismutase activity, and reduced glutathione (GSH) levels, whereas it decreased NOS activity, L-arginine uptake, and lipid peroxidation. To assess the effect of melatonin on glaucomatous neuropathy, weekly injections of HA were performed in the eye anterior chamber. A pellet of melatonin was implanted subcutaneously 24 hr before the first injection or after six weekly injections of HA. Melatonin, which did not affect intraocular pressure (IOP), prevented and reversed the effect of ocular hypertension on retinal function (assessed by electroretinography) and diminished the vulnerability of retinal ganglion cells to the deleterious effects of ocular hypertension. These results indicate that melatonin could be a promissory resource in the management of glaucoma.

Alpha7 nicotinic acetylcholine receptor agonist promotes retinal ganglion cell function via modulating GABAergic presynaptic activity in a chronic glaucomatous model

“…GAD plays an essential role in maintaining a balance between excitation and inhibition in the CNS, and a reduction in GAD expression may cause a decrease in GABA production. In the current study, using a rat model of chronic glaucoma, we presented evidence that glaucomatous neuropathy may involve a decrease in the GABAergic presynaptic activity of RGCs 27, 51 . The reduced retinal GAD65/67 and GABA levels and the decreased GABAergic mIPSC frequencies observed in the glaucomatous retinas in this study are indicative of deficits in retinal GABA synthesis and a conspicuous reduction in GABA release.…”

Associations of sleep duration with open angle glaucoma in the Korea national health and nutrition examination survey

“…[39–42] Melatonin also acts as an antioxidant in the retina, where it scavenges light-induced free radicals and inhibits the nitridergic pathway, [43–46] thereby having a protective effect on the outer membranes of photoreceptors and reversing the effect of ocular hypertension on retinal function. [47] Melatonin also directly and significantly reduces IOP, putatively through the MT3 receptor. [48,49] Reports from various laboratories have correlated the daily onset of melatonin secretion with the onset of nocturnal sleepiness.…”

Melatonin and Its Analog 5-Methoxycarbonylamino-N-Acetyltryptamine Potentiate Adrenergic Receptor-Mediated Ocular Hypotensive Effects in Rabbits: Significance for Combination Therapy in Glaucoma

“…Although there are several risk factors for glaucoma, high IOP remains the major risk factor, and it is the only one currently that can be modified (Crooke et al, 2012a). In this sense, melatonin and its analogs can act as potent neuroprotective agents (Belforte et al, 2010) in addition to reducing IOP. These two facts seem to indicate that melatonin and its derivatives are promising drugs to prevent glaucoma (Agorastos and Huber, 2011;Crooke et al, 2012a).…”