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M.L. Archibald, T.L. LeVatte, B.C. Chauhan; Retinal Ganglion Cell Loss With Low Doses of Endothelin–1 in a Model of Chronic Optic Neuropathy in Rat . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1239.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously described a model of endothelin–1 (ET–1) induced chronic optic neuropathy in rat (Chauhan et al. IOVS 2004;45:144–152) in which ∼ 10–6 M ET–1 produced a reduction in optic nerve head blood flow and caused a time–dependent loss of retinal ganglion cells (RGCs). In the present study we wanted to determine if doses below the threshold for haemodynamic effects were capable of causing RGC loss. Methods: Osmotic minipumps were surgically implanted to deliver 10–7 M (n=5), 10–9 M (n=6) or 10–11 M (n=4) ET–1/day for 28 days to the right retrobulbar optic nerve of adult Brown Norway rats. Before pump implantation, RGCs in both eyes were retrogradely labelled with fluorogold (FG) applied to the superior colliculi. RGC survival was expressed as the ratio of RGC counts in the treated versus control eyes in whole–mounted retinas. Glial activity was assessed in longitudinal sections of optic nerve and retina stained for ED–1 immunoreactivity (n=3, per dose). Results: The mean RGC survival rate for the 10–7, 10–9 and 10–11 M ET–1 doses was 0.83 ± 0.11, 0.76 ± 0.08 and 0.93 ± 0.09 respectively. There were round ED–1 positive cells in the retrobulbar nerve, with the density of labeling decreasing with decreasing ET–1 dose. In the retina, ramified FG–positive cells found in the inner retina co–localised with ED–1 positive cells, indicating the presence of phogocytic microglia or macrophages. Conclusions: Doses of ET–1 that do not have an impact on optic nerve head blood flow lead to mild loss of RGCs with activation of glial cells in the optic nerve and retina. This study supports the hypothesis that ET–1 induced RGC death in this experimental optic neuropathy may be due to factors in addition to, or independent of, optic nerve head ischaemia.
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