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I.A. Bhutto, D.S. McLeod, C.A. Merges, T. Hasegawa, G.A. Lutty; Localization of SDF–1 and CXCR4 Receptor in Aged Human Control Eyes and Eyes With Age–Related Macular Degeneration (AMD) . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5293.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The chemokine stromal cell–derived factor (SDF–1) has a range of biologic activities including regulation of leukocyte trafficking, modulation of hematopoietic cell migration, regulation of angiogenesis, and fetal development. It has been suggested that SDF–1 plays a critical role in recruitment of hematopoietic stem cells and endothelial precursor cells to areas of injury, where these cells participate in compensatory angiogenesis. The purpose of this study was to examine the immunolocalization of SDF–1 and its receptor CXCR4 in the retina and choroid of aged human control donor eyes and in eyes with AMD. Methods: Postmortem ocular tissues from 8 aged control donors (mean age, 79.8 yrs) and from 12 donors with AMD (mean age, 83.9 yrs) were cryopreserved and sectioned. SDF–1 and CXCR4 were localized using streptavidin alkaline phosphatase immunohistochemistry and sections were bleached (Bhutto et al., IOVS. 2004;45:1544). Blood vessels were identified with anti–CD 34 antibody. Three independent observers scored the immunohistochemical reaction product. Results: In aged control eyes, SDF–1 immunoreactivity was observed in internal limiting membrane (ILM) and in large retinal blood vessels, but the interphotoreceptor matrix had the most intense retinal immunostaining. In contrast, the highest expression level of CXCR4 was observed in circulating leukocytes. The most prominent sites of SDF–1 localization in aged control and AMD choroid were retinal pigment epithelial (RPE) cells and choroidal stroma. However, the intensity for SDF–1 was significantly reduced in RPE (p<0.0075) and choroidal stroma (p<0.05) in late AMD eyes. This may be due to a loss in RPE in late AMD. SDF–1 was weak or nearly absent in disciform scars with choroidal neovascularization (CNV). Conclusions: To our knowledge this is the first study of the distribution of SDF–1/CXCR4 in the adult human eye. Our results show that SDF–1/CXCR4 were not be related to early AMD and may not contribute to the formation of CNV in AMD. However, the examples of CNV studied were within disciform scars, so we cannot comment on SDF–1/CXCR4 in developing CNV.
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