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N. Sengupta, S. Caballero, R.N. Mames, E.W. Scott, M.B. Grant; Preventing Stem Cell Incorporation into Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2233.
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Purpose: In the Western world, the primary cause of vision loss for people over the age of 50 is age–related macular degeneration (ARMD). The "wet" form of ARMD is characterized by choroidal neovascularization (CNV) that often leads to severe vision loss. We have previously shown that adult hematopoietic stem cells (HSC) contribute to approximately 50% of newly formed vasculature in the choroid. Stromal–derived factor–1 (SDF–1) is involved with homing and migration of cells from bone marrow to target tissue. Vascular–endothelial cadherin (VE–cadherin, CD144) is involved in endothelial cell adhesion. Preventing homing and/or adhesion of HSC to damaged choroid could reduce CNV. Methods: Lethally irradiated adult C57BL/6J mice were transplanted with purified Lin–Sca–1+ HSC from the bone marrow of green fluorescent protein (gfp) homozygous donor mice. Laser photocoagulation was used to rupture Bruch’s membrane and thereby induce CNV. Animals were injected subretinally with anti–SDF–1, anti–CD144, or saline control or were uninjected before or after laser photocoagulation. The eyes were enucleated and the neural retinas were separated from the RPE/choroid/sclera complex. All tissues were flat–mounted and qualitatively and quantitatively assessed by fluorescence microscopy. Results: Treatment with either antibody significantly reduced the degree of gfp+ stem cell recruitment and incorporation into the CNV lesions, compared to saline control, which had similar quantities of gfp+ cell incorporation as compared to uninjected animals. The efficacy of treatment varied with the time of injection as well as with the effector (anti–SDF–1 or anti–CD144). Conclusions: These results indicate that homing and adhesion of HSC to CNV may be targeted differentially or in combination in order to prevent CNV.
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