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G. Ruiz, B. Feldmann, E. WoldeMussie, J. Burke, L. Wheeler; A Fixed Combination of Brimonidine and Timolol (CombiganTM) Lowers Intraocular Pressure (IOP) and Reduces Retinal Ganglion Cell (RGC) Loss in the Rat Model of Ocular Hypertension. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4205.
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Brimonidine has been reported to be neuroprotective (i.e. protects RGCs) in animal models of ocular hypertension and optic nerve injury (E. WoldeMussie, Minerva Oftalmol 2000:42). This study evaluated a fixed combination of brimonidine 0.2% and timolol 0.5% (CombiganTM) on IOP and RGC survival in the laser-induced rat glaucoma model.
Thirty Wistar rats were divided into five groups of six and laser-treated in OD for induction of OHT, as previously described (WoldeMussie et al IOVS, 2001 Vol. 42) with two laser sessions on Day 1 and Day 7. The five treatment groups were: naïve, PBS, brimonidine 0.2%, timolol 0.5%, and CombiganTM. Animals were dosed with topical eye-drops (5 µL, BID) which began immediately after the 1st laser treatment and continued for the 21 day study. At the end of the study, RGCs were labeled by retrograde transport using crystals of 3000 MW dextran tetramethylrhodamine (DTMR; Molecular Probes). The animals were euthanized 24 hours after labeling, eyes collected and fixed in 4% paraformaldehyde. Retinas were whole-mounted and labeled-RGCs were counted under fluorescent light with Rhodamine filters at 400X magnification. Data are presented as mean (SEM).
One week after the second laser treatment (Day 14), IOP increased two-fold to 30.7 ± 0.7 mm Hg and this pressure remained through Day 21 in the PBS-treated animals. All three actives prevented the rise in IOP with the following ranked order of potency at Day 21: Combigan > brimonidine > timolol. RGC decreased in the PBS-treated animals by 34.3 ± 1.2 %, compared to the naïve untreated eyes. Timolol, brimonidine and CombiganTM decreased RGC counts by 24.3% ± 4.4%, 13 ± 1.9% and 9.1 ± 3.9%, respectively. The RGC responses in the brimonidine and CombiganTM groups were significantly different (p<0.01) from the PBS-treated animals.
Topical administration of a fixed combination of brimonidine and timolol decreased IOP, and was neuroprotective in a rat model of ocular hypertension.
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