Melatonin: a novel neuroprotectant for the treatment of glaucoma.
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.
Belforte
Nicolás A
NA
Department of Human Biochemistry, University of Buenos Aires, CEFyBO/CONICET, Argentina.
Moreno
María C
MC
de Zavalía
Nuria
N
Sande
Pablo H
PH
Chianelli
Mónica S
MS
Keller Sarmiento
María I
MI
Rosenstein
Ruth E
RE
D000818:Animals; D001120:Arginine / Q000378:metabolism; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006651:Histocytochemistry; D007429:Intraocular Pressure / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D012165:Retinal Ganglion Cells; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018696:Neuroprotective Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001120:Arginine; D019001:Nitric Oxide Synthase; D005968:Glutamate Decarboxylase; D008550:Melatonin