Purpose: Recent preclinical studies have shown that treatment with the selective alpha-2 agonist brimonidine up regulates an intrinsic survival pathway that protects the retina and the optic nerve from injury and neuronal death. To test the hypothesis that upregulation of an intrinsic survival pathway may have a lasting neuroprotective effect even after clearance of the drug from the tissue, we examined the effects of brimonidine pretreatment on the survival of RGCs following acute optic nerve injury. The ocular hypertensive rat (OHTR) was used to test brimonidines’s neuroprotective effect in eyes with chronically elevated IOP.
Methods: Brimonidine (0.1 mg/kg, i.p.) was injected 48, 24, 14, or 6 hrs before, or just (0 hrs) after calibrated rat optic nerve crush (Yoles, et.al., IOVS, 1999). The methods of Woldemussie (IOVS, abst 4410, 2000) were used to develop the OHTR.
Results: Significant neuroprotection was seen with treatment at 48, 24, 14 and 6 hours prior to injury. To examine neuroprotection in a more chronic injury model, IOP was elevated >2-fold in rats. After three weeks, rats with elevated IOP treated with or without vehicle (control) lost 35% of their RGCs. Rats receiving constant brimonidine treatment (1mg/1kg/day by osmotic pump) lost only 12% of their RGCs.
Conclusion: These data increase our understanding of brimonidine’s neuroprotective activity in both acute and more chronic retinal and optic nerve injuries.