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Abstract #18374 Published in IGR 3-3
Neuroprotection of retinal ganglion cells by brimonidine in rats with laser-induced chronic ocular hypertension
Woldemussie E; Ruiz G; Wijono M; Wheeler LAInvestigative Ophthalmology and Visual Science 2001; 42: 2849-2855
PURPOSE: To examine the neuroprotective effect of the α2-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 whole-mounted retinas. Brimonidine or timolol was administered, either at the time of or ten days after IOP elevation, and continued for three weeks. Drug-related immunohistochemical changes in glial fibrillar acidic protein (GFAP) were also determined after three weeks. RESULTS: Laser treatment caused a two-fold IOP increase over baseline that was maintained for two months. A time-dependent loss of ganglion cells occurred with elevated IOP. Systemic administration of brimonidine or timolol caused little decrease in IOP. After three weeks of elevated IOP, ganglion cell loss 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 ten days after IOP elevation prevented any further loss of ganglion cells. In vehicle- or timolol-treated rats, ganglion cell loss continued to 33%. The increase in immunoreactivity of GFAP in ocular hypertensive retinas was attenuated by brimonidine. CONCLUSIONS: Systemic application of brimonidine or timolol had little effect on IOP. Brimonidine, but not timolol, showed significant protection of retinal ganglion cells when applied at the time of IOP elevation, and prevented further cell loss when applied after IOP was elevated. This indicates that brimonidine has a neuroprotective activity unrelated to its effect on ocular hypotension.
Dr E. WoldeMussie, Department of Biological Sciences, Allergan, Inc., 2525 Dupont Drive, Irvine, CA 92612-1599, USA. woldemussie_liz@allergan.com
Classification:
11.3.3 Apraclonidine, brimonidine (Part of: 11 Medical treatment > 11.3 Adrenergic drugs)