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K. Yoneda, M. Kamei, N. Kume, T.–I. Matsuda, H. Sakaguchi, M. Suzuki, H. Itabe, S. Yonehara, T. Kita; Oxidized Lipoprotein and its Scavenger Receptors in Choroidal Neovascularization of Age–Related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1783.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Oxidative stress has been implicated in the pathogenesis of age–related macular degeneration (AMD). Co–localization between lipoprotein–containing debris and macrophages in AMD has also been indicated histophthologically. However, little is known about the disease progress. We hypothesize that macrophages may accumulate to scavenge oxidized lipoprotein in AMD. In this study, therefore, we investigated whether oxidized lipoprotein and its scavenger receptors are present in AMD, and identified cells expressing oxidized low density lipoprotein (Ox–LDL) specific cell–surface receptors. Methods: Immunohistochemistry was performed with DLH3, anti–Ox–LDL antibody, on four surgically excised choroidal neovascular (CNV) membranes. Double–stained immunohistochemistry was then performed using antibodies against scavenger receptors and cell markers. We applied antibodies against LOX–1 (lectin–like Ox–LDL receptor–1) or SR–PSOX (scavenger receptor that binds phosphatidylserine and oxidized lipoprotein) to detect scavenger receptors, and antibodies against pancytokeratin, CD68 or von Willebrand factor to identify retinal pigment epithelium (RPE), macrophages and vascular endothelial cells, respectively. Results: Ox–LDL was present in all CNV membranes, and its scavenger receptors, SR–PSOX and LOX–1, also showed localized immunoreactivity. Cells that expressed SR–PSOX were suspected to be dominantly macrophages and partially vascular endothelial cells. Cells that expressed LOX–1 were suspected to be macrophages, RPE and vascular endothelial cells. Almost all macrophages expressed these scavenger receptors to Ox–LDL. Conclusions: Ox–LDL exists in AMD lesion and the macrophages accumulating there express cell surface scavenger receptors for Ox–LDL. These findings are consistent with the concept that oxidatively modified lipoproteins and response to them may have a role in pathogenesis.
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