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Joshua M. Barnett, Gary W. McCollum, John S. Penn; Blocking Endoglin Reduces Endothelial Progenitor Cell Angiogenic Capacity and Retinal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3018.
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Angiogenesis and neovascularization (NV) are common pathological processes in age-related macular degeneration and neovascular retinopathies. Endoglin (CD105) expression has been reported as being upregulated in proliferative tumor vasculature, and, as an auxiliary receptor in the TGFβ super family, it is suggested to be involved in cell proliferation, migration and differentiation. This study sought to examine the contribution of endoglin to endothelial progenitor cell (EPC) angiogenic activity and retinal NV.
Sprauge-Dawley rat litters were exposed to alternating 50% and 10% oxygen atmospheres from birth through P14. Upon removal from the exposure chamber, some rats received an intraperitoneal injection of a CXCR4 antagonist (inhibitor of EPC homing), AMD3100, at post-oxygen days 0 and 3. Other animals received intravitreal injections of vehicle, anti-VEGF, or anti-CD105. These animals were sacrificed at 6 days later, and their retinas were ADPase-stained and evaluated for NV and avascular area. The AMD3100-treated animals were sacrificed at 3 and 6 days post-oxygen exposure, and retinal CD105 levels were measured by ELISA.
Endoglin protein was found to be upregulated 4.8-fold in retinal tissue from oxygen-exposed rats relative to control animals (p<0.01). This increase in endoglin was reduced 56% in animals treated with a CXCR4 antagonist (AMD3100), presumably by inhibition of EPC homing to neovascular areas (p<0.02). Anti-CD105 treatment reduced in vivo NV by 46% at the highest concentration (p<0.05) and worked additively with anti-VEGF treatment to reduce NV by an additional 23% (p<0.05).
Anti-CD105 was found to be effective in reducing neovascular lesion size in oxygen-exposed rats and worked additively with anti-VEGF treatments. Endoglin plays an angiogenic role in retinal NV, and blocking endoglin function is an effective method of reducing NV, partially through a reduced angiogenic capacity of EPCs.
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