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S. Nizari, L. Guo, W. Cheung, M. F. Cordeiro; Systemic Brimonidine Is Neuroprotective in Abeta-Induced RGC Apoptosis in vivo Model of Neurodegeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4045.
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We have recently demonstrated that beta-Amyloid (Abeta), the protein forming Alzheimer plaques, is neurotoxic and showed that intravitreal Abeta induces RGC apoptosis in the rat retina in a time- and dose- dependent manner. In this study, we investigate the effects of systemic brimonidine on Abeta-induced RGC apoptosis using our recently described model of neurodegeneration .
Dark Agouti (DA) rat eyes were imaged at baseline and then randomly assigned to treatment with intraperitoneal brimonidine (1mg/kg, 0.1 mg/kg and vehicle) at the same time as 25nmol Aß25-35 was given intravitreally. 3 days following intravitreal Aß25-35, animals were DARC imaged again following which they were killed for histological assessment. The number of apoptotic RGCs were counted as we have previously described, by observers masked to treatment protocols. Statistical analysis were performed by using ANOVA.
Low dose brimonidine (0.1 mg/kg ip) significantly reduced RGC apoptosis compared to both high dose (1.0 mg/kg) (p= 0.0021) and vehicle control (p= 0.0041). Reductions in the levels of RGC apoptosis compared to control were 67.1 % in the low dose brimonidine (0.1 mg/kg ip) compared to 8.7% in the high dose (1.0 mg/kg) group, with efficacy demonstrated both in vivo and histologically.
These results show that low dose systemic brimonidine (0.1 mg/kg ip) has a neuroprotective effect on Abeta-induced RGC apoptosis in vivo. 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. As we have recently implicated Abeta in OHT-induced RGC apoptosis, our results suggest a mechanism by which brimonidine may be neuroprotective in glaucoma.
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