Neuroprotective effects of alpha(2)-selective adrenergic agonists against ischemia-induced retinal ganglion cell death

PURPOSE. To investigate in adult rats the effects of two alpha (2)-selectiv e 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 su perior colliculi. Seven days later, the left ophthalmic vessels were ligate d 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 i schemia. 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-label ed cells in 12 standard retinal areas. RESULTS. Seven days after 60 or 90 minutes of retinal ischemia death had oc curred in 36% or 47%, respectively, of the RGC population, and by 21 days t he loss of RGCs amounted to 42% or 62%, respectively. Systemic pretreatment with an alpha (2)-SA resulted in enhanced survival of ischemic-injured RGC s. Topical pretreatment with an alpha (2)-SA prevented up to 100% of the is chemia-induced RGC loss. Pretreatment with an alpha (2)-SA abolished the se condary slow RGC loss that occurred between days 7 and 21 after ischemia. W hen administered shortly after ischemia (up to 2 hours) AGN 190342 rescued substantial proportions of RGCs destined to die and diminished slow RGC dea th. CONCLUSIONS. Pretreatment and early posttreatment with an alpha (2)-SA indu ces marked long-lasting neuroprotective in vivo protection against ischemia -induced cell death in RGCs.