Neuro-protection of retinal ganglion cells by brimonidine in rats with laser-induced chronic ocular hypertension

PURPOSE. To examine the neuroprotective effect of the alpha (2)-adrenergic agonist brimonidine in a chronic ocular hypertension model. METHODS. Intraocular pressure (IOP) was elevated by laser photocoagulation of episcleral and limbal veins. Retinal ganglion cell loss was evaluated in wholemounted retinas. Brimonidine or timolol was administered, either at t he time of or 10 days after IOP elevation and continued for 3 weeks. Drug-r elated immunohistochemical changes in glial fibrillary acidic protein (GFAP ) were also determined after 3 weeks. RESULTS. Laser treatment caused a twofold IOP increase over baseline that w as maintained for 2 months. A time-dependent loss of ganglion cells occurre d with elevated IOP. Systemic administration of brimonidine or timolol caus ed little decrease in IOP. After 3 weeks of elevated IOP, ganglion cell los s in control rats was 33% +/- 3%. Brimonidine reduced the progressive loss of ganglion cells to 26% +/- 1% and 15% +/- 2% at doses of 0.5 and 1 mg/kg . d, respectively. Timolol had no effect. Ten days of high IOP resulted in 22% +/- 4% ganglion cell loss. Brimonidine administration initiated 10 days after IOP elevation prevented any further loss of ganglion cells. In vehic le- or timolol-treated rats, ganglion cell loss continued to 33%. The incre ase in immunoreactivity of GFAP in ocular hypertensive retinas was attenuat ed by brimonidine. CONCLUSIONS. Systemic application of brimonidine or timolol had little effe ct on IOP. Brimonidine, but not timolol, showed significant protection of r etinal ganglion cells when applied at the time of IOP elevation and prevent ed further cell loss when applied after IOP was elevated. This indicates th at brimonidine has a neuroprotective activity unrelated to its effect on oc ular hypotension.