Neuroprotective effects of α2-selective adrenergic agonists against ischemia-induced retinal ganglion cell death

PURPOSE. To investigate in adult rats the effects of two alpha (2)-selective adrenergic agonists (alpha (2)-SAs; AGN 191103 and AGN 190342) on retinal ganglion cell (RGC) survival after transient retinal ischemia. METHODS. RGCs were labeled with a Fluorogold (FG) tracer applied to both superior colliculi. Seven days later, the left ophthalmic vessels were ligated for 60 or 90 minutes. In one group, a single dose of saline or one alpha (2)-SA was administered intraperitoneally (IP) or topically 1 hour before ischemia. In another group, a single dose of AGN 190342 was administered IP, 1, 2, 4, 24, or 72 hours after ischemia. Rats were processed 7, 14, or 21 days later. Densities of surviving RGCs were estimated by counting FG-labeled cells in 12 standard retinal areas. RESULTS. Seven days after 60 or 90 minutes of retinal ischemia death had occurred in 36% or 47%, respectively, of the RGC population, and by 21 days the loss of RGCs amounted to 42% or 62%, respectively. Systemic pretreatment with an alpha (2)-SA resulted in enhanced survival of ischemic-injured RGCs. Topical pretreatment with an alpha (2)-SA prevented up to 100% of the ischemia-induced RGC loss. Pretreatment with an alpha (2)-SA abolished the secondary slow RGC loss that occurred between days 7 and 21 after ischemia. When administered shortly after ischemia (up to 2 hours) AGN 190342 rescued substantial proportions of RGCs destined to die and diminished slow RGC death. CONCLUSIONS. Pretreatment and early posttreatment with an alpha (2)-SA induces marked long-lasting neuroprotective in vivo protection against ischemia-induced cell death in RGCs.