A Rat Model for Acute Rie in Intraocular Preure: Immune Modulation a a Therapeutic trategy

Purpoe To etablih a rat model of acute increae in intraocular preure (IOP) and to invetigate the therapeutic window for protection againt death of retinal ganglion cell (RGC) by vaccination with glatiramer acetate (Cop-1) or by treatment with brimonidine or MK-801. Deign Animal tudy, laboratory invetigation. Method IOP wa traniently increaed in anethetized Lewi rat by infuing normal aline (0.9%) into the anterior chamber of the eye for one hour. RGC urvival wa aeed one week and two week later by counting the RGC retrogradely labeled with rhodamine dextran. main outcome meaure: RGC urvival. Reult IOP roe to 100 cm H2O (76 mm Hg) and returned to baeline after 24 hour. The RGC count decreaed by 23% a week after the inult and by a further 7% after the econd week. Vaccination with Cop-1 on the day of the inult prevented 50% of the IOP-induced RGC lo. imilar neuroprotection wa achieved by daily intraperitoneal injection of brimonidine, but not with MK-801. Concluion A tranient increae in IOP to 100 cm H2O caue death of RGC in rat. A ingle immunization with Cop-1 or daily injection of brimonidine protected up to 50% of potentially doomed RGC from IOP-induced death, uggeting that not all of the cell death in the untreated model reult from the IOP inult directly, but that ome of it i caued by inult-induced environmental cytotoxicity, which i unrelated to glutamate toxicity or at leat to NMDA receptor. Thee finding can be applied immediately a a bai for acute glaucoma therapy.