Retinal ganglion cell death induced by retinal ischemia: Neuroprotective effects of two alpha-2 agonists

We have investigated in adult Sprague-Dawley rats the neuroprotective effec ts of true alpha -2-selective agonists [AGN 191,103 (AGN) and brimonidine t artrate (BMD)I on retinal ganglion cell (RGC) survival after transient reti nal ischemia. RGCs were labelled with Fluorogold (FG) applied to both super ior colliculi. Seven days later, 90 min of retinal ischemia were induced in the left eyes by ligature of the ophthalmic vessels (LOV). In one group of animals, vehicle or AGN (0.01 mg/kg) were administered systemically 1 hr b efore ischemia. In another group of animals, two 5 mul drops of vehicle, AG N (0.05%) or BMD (0.1%) were administered topically in the left rye 1 hr be fore ischemia. The animals were processed 7 or 21 days later. RGC survival was estimated by counting FG-labelled cells in 12 standard areas of each re tina. In control retinas of systemically pretreated animals, mean densities of labelled RGCs were 2372 +/- 49 cells/mm(2) (mean +/- SEM; n = 6). In ex perimental retinas of systemically pretreated animals, mean RGC densities h ad decreased 7 days after ischemia to 53% in = 6) or 81% (n = 6) of control in the groups treated with vehicle or AGN, respectively. Twenty-one days a fter ischemia, mean RGC densities had decreased to 38% (n = 6) or 79% (n = 6) of control in the groups treated with vehicle or AGN, respectively. In c ontrol retinas of topically pretreated animals, mean densities of labelled RGCs were 2208 +/- 29 cells/mm(2) in = 6). In experimental retinas of topic ally pretleated animals, mean RGC; densities had decreased 7 days after isc hemia to 54% (n = 6),95% in = 6) or 96% (n = 6) of control in the groups tr eated with vehicle, AGN or BMD, respectively. These results indicate that p retreatment with a single systemic or topical dose of AGN or BMD can preven t completely the early rapid phase of RGC loss and abolish the delayed RGC loss observed after 90 min of retinal ischemia induced by ligature of the o phthalmic vessels. (C) 2001 by Elsevier Science Inc. All rights reserved.