Protective role of melatonin on retinal ganglionar cells: in vitro an in vivo evidences

DIAZ DE BARBOZA, G; CARPENTIERI AGATA; DIAZ FAJRELDINES HUGO; ALLEMANDI DANIEL; BESSONE CAROLINA; TOLOSA DE TALAMONI N; QUINTEROS DANIELA

LIFE SCIENCES

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2019 vol. 218 p. 233 - 240

0024-3205

Oxidative stress triggers ocular neurodegenerative diseases, such as glaucoma or macular degeneration. Theincrease of reactive oxygen and nitrogen species in retinal ganglion cells (RGCs) causes damage to the structureand function of the axons that make up the optic nerve, leading to cell death arising from apoptosis, necrosis orautophagy in the RCGs. The use of antioxidants to prevent visual neurodegenerative pathologies is a novel andpossibly valuable therapeutic strategy. To investigate in vitro and in vivo neuroprotective efficacy of melatonin(MEL) in RGCs, we used a model of oxidative glutamate (GLUT) toxicity in combination with L-butionin-S, Rsulfoximine(BSO), which induces cell death by apoptosis through cytotoxicity and oxidative stress mechanisms.Histological sectioning and immunohistochemical assays using the TUNEL technique were performed to determinethe damage generated in affected cells and to observe the death process of RGCs. Whit BSO-GLUT theresults revealed a progressive RGCs death without any significant evidence of a decreased retinal function after9 days of treatment. In this way, we were able to develop a retinal degeneration model in vivo to carry outtreatment with MEL and observed an increase in the survival percentage of RGCs, showing that BSO-GLUT couldnot exert an oxidant effect on cells to counteract the effect of MEL. These findings reveal that MEL has a neuroprotectiveand antiapoptotic effect as evidenced by the reduction of oxidative stress damage. MEL demonstratedin this model makes it a promising neuroprotective agent for the treatment of ocular neurodegenerativediseases when administered locally.