Neuroprotective effects of brimonidine against transient ischemia-induced retinal ganglion cell death: a dose response in vivo study.
The purpose of this study was to investigate the dose-response effects of topically administered brimonidine (BMD) on retinal ganglion cell (RGC) survival, short and long periods of time after transient retinal ischemia. In adult Sprague-Dawley rats, RGCs were retrogradely labeled with the fluorescent tracer fluorogold (FG) applied to both superior colliculi. Seven days later, the left ophthalmic vessels were ligated for 90 min. One hr prior to retinal ischemia, two 5 microl drops of saline alone or saline containing 0.0001, 0.001, 0.01 or 0.1% BMD were instilled on the left eye. Rats were processed 7, 14 or 21 days later and densities of surviving RGCs were estimated by counting FG-labeled RGCs in 12 standard regions of each retina. The following have been found. (1) Seven days after 90 min of transient ischemia there is loss of approximately 46% of the RGC population. (2) topical pre-treatment with BMD prevents ischemia-induced RGC death in a dose-dependent manner. Administration of 0.0001% BMD resulted in the loss of approximately 37% of the RGC population and had no significant neuroprotective effects. Administration of higher concentrations of BMD (0.001 or 0.01%) resulted in the survival of 76 or 90%, respectively, of the RGC population, and 0.1% BMD fully prevented RGC death in the first 7 days after ischemia. (3) Between 7 and 21 days after ischemia there was an additional slow cell loss of approximately 25% of the RGC population. Pre-treatment with 0.1% BMD also reduced significantly this slow cell death. These results indicate that the neuroprotective effects of BMD, when administered topically, are dose-dependent and that the 0.1% concentration achieves optimal neuroprotective effects against the early loss of RGCs. Furthermore, this concentration is also effective to diminish the protracted loss of RGCs that occurs with time after transient ischemia.
Lafuente
M P
MP
Laboratorio de Oftalmología Experimental, Departamento de Oftalmología, Universidad de Murcia, E-30.100 Espinardo, Murcia, Spain
Villegas-Pérez
M P
MP
Mayor
S
S
Aguilera
M E
ME
Miralles de Imperial
J
J
Vidal-Sanz
Manuel
M
D000287:Administration, Topical; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000818:Animals; D000068438:Brimonidine Tartrate; D016923:Cell Death; D004305:Dose-Response Relationship, Drug; D007511:Ischemia / Q000150:complications* / Q000473:pathology; D008856:Microscopy, Fluorescence; D011810:Quinoxalines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology*; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D000068438:Brimonidine Tartrate