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W. Shen, S. H. Chung, L. Zhu, M. C. Gillies; Erythropoietin Stabilizes Retinal Vasculature and Improves Vascular Lesions in RCS Rats. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3660.
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© ARVO (1962-2015); The Authors (2016-present)
Royal College of Surgeons (RCS) rats develop progressive retinal neuronal damage and vascular abnormalities. The aim of this study was to investigate if erythropoietin (EPO) is effective in protecting retinal vasculature from damage in RCS rats.
Fundus fluorescein angiography (FFA) was employed to monitor dynamic retinal changes in RCS rats from 6 to 25 weeks of age. Confocal microscopy was performed with frozen sections using antibodies for changes in the retinal glia [glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), vimentin and OX-42], retinal vasculature (collagen IV) and expression of vascular endothelial growth factor (VEGF) and pigment epithelium derived growth factor (PEDF). To study the effect of EPO treatment on retinal vascular rescue, EPO was injected intraperitoneally in RCS rats at 14 weeks of age with a dose of 5000IU/kg, twice a week for 4 consecutive weeks. Changes in the retinal vasculature, glia and recruitment of CD34+ endothelial progenitor cells into the retina were examined by FFA and confocal microscopy using frozen sections and flatmounted retinas.
RCS rats developed progressive vascular lesions from 3 months of age, which were predominantly confined to regions surrounding the optic disc. Changes in the retinal vasculature were accompanied by progressive disruption of the retinal glia (astrocytes, Müller cells and OX-42+ microglial cells), increased expression of VEGF and decreased expression of PEDF. Immunostaining for collagen IV showed subretinal vascular abnormalities. Quantitative image analysis demonstrated that EPO treatment significantly reduced the area of vascular lesions and stabilized both superficial and deep retinal vascular plexuses. Immunohistochemical studies revealed that EPO reduced retinal glial swelling and increased the number of OX-42+ and CD34+ cells in the inner retina but most CD34+ cells failed to incorporate into the retinal vasculature.
EPO may have valuable therapeutic potentials for retinal vascular rescue via modulating retinal glia and bone marrow derived progenitor cells in pathological conditions.
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