title: Effect of memantine: A NMDA receptor blocker, on ethambutol-induced retinal injury.
abstract: Ethambutol (ETM)-induced retinal injury is associated with a deterioration in visual function caused by a mechanism similar to many other retinal injuries; i.e. glutamate-induced N-methyl-d-aspartate (NMDA) receptor hyperexitability. Therefore, the current study was carried out to investigate the effect of memantine (MEM), NMDA receptor blocker, on ETM-induced retinal injury. A total of 36 rats were divided equally into: group I, control, group II (ETM administration, 100mg/kg/d, orally for 4 weeks) and group III (administration of ETM+MEM, 100 and 5mg/kg/d, respectively, orally for 4 weeks). Specimens of the retina were prepared for histological study by haematoxylin, eosin (H&E) as well as for immunohistochemical study by Bcl-2, cleaved caspase-3 and glial fibrillary acidic protein (GFAP). In the ETM group, the neural retina became significantly thinner (p<0.05) and the ganglion cell layer (GCL) was the main layer affected in the form of a significant decrease (p<0.001) in its cellularity, along with an obvious increase in Bcl-2 and GFAP expression as well as caspase-3 and oxidative stress markers level compared with other groups. On the other hand, on combining MEM with ETM, the retinal thickness, NFL appearance and GCL cellularity returned to amounts nearly similar to the control group coupled with a significant decrease (p<0.05) in the detected caspase-3, Bcl-2 levels and minimal GFAP expression. Therefore, memantine could be an effective neuroprotective agent in ETM-induced retinal injury by a mechanism that may involve correction of the pro/anti-apoptotic pathways and normalization of the oxidative and Müller cell stress responses.
authors.affiliation: Department of Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Electronic address: drahmadabdelhamid@gmail.com.
authors.forename: Ahmed A M
authors.initials: AA
authors.lastname: Abdel-Hamid
authors.affiliation: Department of Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Alaa El-Din L
authors.initials: Ael-D
authors.lastname: Firgany
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Eyad M T
authors.initials: EM
authors.lastname: Ali
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D004977:Ethambutol; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012160:Retina / Q000473:pathology; D012167:Retinal Perforations / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016194:Receptors, N-Methyl-D-Aspartate; D004977:Ethambutol; C505410:Casp3 protein, rat; D053148:Caspase 3; D008559:Memantine
keywords: Bcl-2; Ethambutol; GFAP; Memantine; NMDA receptors; Neural retina