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S. Caballero, N. Sengupta, R.N. Mames, E.W. Scott, M.B. Grant; Stem Cell Recruitment and Participation in Choroidal Neovascularization Following Rupture to Bruch's Membrane . Invest. Ophthalmol. Vis. Sci. 2003;44(13):546.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Age related macular degeneration (AMD) is the leading cause of new blindness in the elderly. Choroidal neovascularization (CNV) is responsible of 80% of severe visual loss in patients with AMD. We have previously shown that adult hematopoietic stem cells (HSC) can function as hemangioblasts, making both blood and preretinal blood vessels (Nat Med 2002, 8:607). We now asked whether hemangioblasts could participate in choroidal neovascularization. Methods: C57/Bl6J animals were long-term engrafted with purified (Lin-/Sca-1+) HSC from green fluorescent protein (gfp) transgenic mice, then subjected to rupture of Bruch’s membrane by laser photocoagulation at three sites in each eye. After 21 days, the animals were perfused with rhodamine-labeled dextran, enucleated and the retina was dissected and mounted flat. The area of CNV at each rupture site was evaluated by confocal microscopy. Results: Hemangioblast activity in adult mice resulted in the formation of functional gfp+ vasculature. These new vessels were concentrated at the sites of injury and spread radially. All animals showed robust hemangioblast activity in the retinal tissues at the sites of Bruch’s membrane rupture. Conclusion: Current treatments for CNV are ineffective because they are directed at ablating the new vessels rather than addressing the underlying angiogenic stimuli. These treatments also do not consider the potential sources of new blood vessels, i.e. resident endothelial proliferation versus recruitment of endothelial precursors. Laser injury to Bruch’s membrane resulted in sufficient injury to induce HSC transdifferentiation and incorporation into CNV. These data indicate that recruitment of circulating hemangioblasts to areas of retinal injury may be important to the pathogenesis of CNV. This observation suggests a new therapeutic target for AMD.
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