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A. Vogel, G. Zahn, F.G. Holz, K.U. Loeffler; Integrin 5ß1 in Choroidal Neovascular Membranes Associated With Age–Related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5051.
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To determine the presence and evaluate the possible role of integrin α5ß1 in neovascular tissue associated with age–related macular degeneration (AMD).
Paraffin sections of 7 formalin–fixed choroidal neovascular membranes (CNV) which were removed during subretinal surgery for neovascular AMD were investigated. As a positive control for neovascularization in other ocular samples, similarly processed tissue from 3 pyogenic granulomas was used. Furthermore, sections from 6 eyes enucleated for end–stage glaucoma (one of which, in addition, revealed a typical AMD lesion) were also examined, in particular with regard to the presence of integrin α5ß1 in normal choroidal vessels and choriocapillaries. Immunohistochemistry was performed using 3 different antibodies (Abs) to integrin α5ß1 (2 polyclonal and 1 monoclonal) as well as Abs to Factor VIII (endothelial cell marker), CD68 (macrophage marker) and CK 18 (RPE cell marker) on adjacent sections for comparison. The reaction product was visualized using AEC.
In pyogenic granuloma, there was intense labeling with anti–integrin α5ß1 of all endothelial cells as well as some macrophages/inflammatory cells within the stroma. This was confirmed by a similar reaction using anti–Factor VIII and anti–CD68 on adjacent sections. Sections from the enucleated eyes all revealed some anti–integrin α5ß1 immunoreactivity in normal choroidal vessels while choriocapillary vessels were mostly negative. In CNV, anti–integrin α5ß1 labeling was seen in most vascular structures and was more prominent than in normal choriocapillaries but less intense compared to labeling with anti–Factor VIII. Individual cells, most likely of macrophage origin, were also stained but even more prominent labeling was found in retinal pigment epithelial (RPE) cells within these membranes. This staining pattern was similar in the eye with AMD while no significant labeling of RPE cells away from the lesion (presumably normal RPE) nor in RPE cells in glaucomatous eyes was seen.
New vessels in CNV exhibit more prominent anti–integrin α5ß1 immunoreactivity compared to normal choriocapillaries. The difference appears even more striking with regard to RPE cells from AMD lesions compared to normal RPE. From our findings we therefore conclude that an upregulation of integrin α5ß1 in RPE cells might play an important role in the development of CNV associated with AMD.
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