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Mohammadali Almasieh, Mylène Pouliot, Melanie Kelly, Elvire Vaucher, Adriana Di Polo; Retinal Ganglion Cell Survival Correlates with Retinal Microvasculature Protection and Blood Flow Restoration in Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2608.
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© ARVO (1962-2015); The Authors (2016-present)
The relationship between neuronal and vasculature degeneration in glaucoma is not well understood. We previously demonstrated that the acetylcholinesterase inhibitor galantamine protects retinal ganglion cells (RGCs) in experimental glaucoma. Here, we asked whether galantamine-induced neuroprotection correlates with changes in the retinal microvasculature and blood flow.
Ocular hypertension (OHT) was induced by injection of a hypertonic saline solution into an episcleral vein in Brown Norway rats. Daily galantamine treatment began on the first day of OHT and continued thereafter (3.5 mg/kg, i.p.). The retinal microvasculature density was quantified using isolectin, and the regional ocular blood flow was assessed by quantitative autoradiography using N-isopropyl-p-14C-iodoamphetamine ([14C]-IMP). Ex vivo experiments were carried out on isolated retinal arterioles. Neuroprotection was evaluated by quantification of RGC soma and axons, and by recording visual evoked potentials (VEPs) from the superior colliculus.
RGC death was accompanied by a dramatic reduction in the density of the retinal microvasculature and blood flow. Galantamine-mediated protection of RGCs (70%, n=10) correlated with the preservation of retinal capillaries (75%, n=6) compared to vehicle-treated controls (37% RGCs, n=9; 40% vessels, n=6) at 5 weeks of OHT. Furthermore, vasculature protection correlated with marked restoration of blood flow in glaucomatous eyes (82%, n=4) compared to control eyes (42%, n=4); and recovery of the VEP in the corresponding superior colliculi. Consistent with an increase in blood flow, galantamine induced vasodilation in isolated retinal arterioles pre-constricted with endothelin-1. Blockers of muscarinic ACh receptors (mAChR) inhibited the neuro- and vaso-protective effects of galantamine.
Our study supports a tight relationship between neuronal and vascular preservation in experimental glaucoma. We also demonstrate a role for galantamine in RGC and vascular protection via mediated mAChR activation.
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