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S. Nizari, L. Guo, M. F. Cordeiro; Systemic Brimonidine is Neuroprotective in OHT-Induced RGC Apoptosis in vivo. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3185.
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Brimonidine (BMD) has been shown to be neuroprotective via a number of different mechanisms. It is used topically in glaucoma for lowering intraocular pressure, although this effect is believed to be limited on systemic administration. Here, we investigate intraperitoneal BMD and RGC apoptosis in a rat model of ocular hypertension.
Using our established chronic ocular hypertension (OHT) rat model, IOP was induced in 36 animals, with DARC imaging performed at 3 and 8 weeks after IOP elevation. Animals were randomly assigned to no treatment (untreated OHT) or intraperitoneal BMD (0.1 mg/kg) at singly time of IOP elevation (single, BMD) or multiple doses at surgery and 1 & 2 weeks later (multiple, BMD). The IOP of both eyes in each rat was measured regularly using a Tonolab pen. Mean values were calculated with 95% confidence intervals for the absolute counts. All treatment groups were compared to each other and control using ANOVA. The percentage reduction in RGC apoptosis associated with treatment and compared to control were calculated, as we have previously described.
Both single and multiple BMD treatments induced a significant reduction in RGC apoptosis at 3 and 8 weeks after IOP elevation compared to control (p<0.001). Interestingly there was no difference between single or multiple treatment regimens at either time point. There was no statistical difference between IOPs between treatment groups.
Systemic brimonidine treatment appears to very effectively inhibit RGC apoptosis in our experimental OHT model, and its effects are not related to intraocular pressure. More importantly, its effect is prolonged, with efficacy demonstrable even after 8 weeks with a single application. Our results are consistent with previous published results, the most recent being from Hernandez et al , who showed a non-IOP dependent neuroprotective effect of systemic brimonidine in an experimental model of OHT.
M. Hernandez et al, Experimental Eye Research 86 (2008) 798-806.
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