Melatonin Prevents Functional and Histological Alterations in an Experimental Model of Glaucoma in Rats

ROSENSTEIN, RUTH; BELFORTE, NICOLAS; DE ZAVALÍA NURIA; KELLER SARMIENTO, MARIA; MORENO, MARIA

Fort Lauderdale, USA

Congreso; The Association for Research in Vision and Ophthalmology; 2009

The Association for Research in Vision and Ophthalmology

Invest Ophthalmol Vis Sci 2009;50: E-Abstract 2765.© 2009 ARVO 2765—D689 Melatonin Prevents Functional and Histological Alterations in an Experimental Model of Glaucoma in Rats R. E. Rosenstein, N. Belforte, N. de Zavalía, M. I. Keller Sarmiento and M. C. Moreno Dept Human Biochem-Sch Med/ UBA-CEFyBO/CONICET, University of Buenos Aires, Buenos Aires, Argentina Commercial Relationships: R.E. Rosenstein, None; N. Belforte, None; N. de Zavalía, None; M.I. Keller Sarmiento, None; M.C. Moreno, None. Support: Ruth Rosenstein, BID 1728 PICT 25364 Abstract Purpose:An increase in retinal glutamate and nitric oxide levels, as well as oxidative damage could be involved in glaucomatous neuropathy. The aim of the present work was to investigate the effect of melatonin on these parameters as well as on functional and histological alterations in an experimental model of glaucoma induced by chronic injections of hyaluronic acid (HA) Methods:In retinas from normotensive eyes, glutamate uptake and glutaminase activity were assessed using 3H-glutamate and 3H-glutamine, respectively. NOS activity was measured through the conversion of 3H-arginine to 3H-citrulline. Superoxide dismutase (SOD), glutamine synthetase (GS) activity, and reduced glutathione levels (GSH) were measured by spectrophotometric methods, while thiobarbituric acid reactive substances (TBARS) levels were determined as an index of lipid peroxidation. On the other hand, weekly injections of HA were performed unilaterally in the rat anterior chamber, whereas the contralateral eye was injected with saline solution. A pellet of 5 mg melatonin was implanted subcutaneously two hours before the first injection of HA. The pellet of melatonin was replaced every 15 days. After 6 or 10 weeks of ocular hypertension retinal function was assessed by electroretinography, and the ganglion cell layer cells number was measured. Results:Melatonin increased glutamate uptake, GS and SOD activities, as well as GSH levels. Moreover, melatonin decreased glutaminase and NOS activities and lipid peroxidation. On the other hand, melatonin significantly prevented the electroretinographic dysfunction and the decrease in the number of retinal ganglion cells induced by ocular hypertension Conclusions:The chronic treatment with melatonin prevented functional alterations and diminished the vulnerability of retinal ganglion cells to the deleterious effects of ocular hypertension, probably by antagonizing the effect of ocular hypertension on glutamatergic and nitridergic systems and on oxidative damage. Therefore, these results indicate that melatonin could be a promissory resource in the management of glaucoma Keywords: melatonin • neuroprotection • retina: neurochemistry © 2009, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.