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K. Klatt, G. Zahn, J. S. Heier, P. E. Daniel, Jr., P. Pour Nouroz, F. G. Holz, K. U. Loeffler; Integrin 5ß1 (I5ß1) in Preretinal Membranes Associated With Proliferative Vitreoretinopathy (PVR). Invest. Ophthalmol. Vis. Sci. 2007;48(13):1233.
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Iα5ß1 is supposed to play an important role in neovascularization and has been shown to be present in subretinal neovascular membranes associated with age-related macular degeneration. In this study, we determined the presence and evaluated the possible role of Iα5ß1 in tissue associated with PVR.
Paraffin sections of 12 formalin-fixed preretinal membranes from 10 patients were investigated. Surgery was performed for idiopathic posterior PVR in 4 patients, for PVR after retinal detachment in 1 patient and for diabetic PVR in 1 patient. One eye enucleated for neovascular glaucoma, exhibiting a prominent preretinal neovascular membrane, was also examined. Immunohistochemistry was performed using 3 different antibodies (Abs) to Iα5ß1 (2 poly- 1 monoclonal) as well as Abs to Factor VIII (endothelial cell marker), CD68 (macrophage marker) and CK18 (RPE cell marker) on adjacent sections for comparison. As a positive control for Iα5ß1 labeling in other ocular samples, similarly processed tissue from 3 pyogenic granulomas was used. Sections from eyes enucleated for choroidal melanoma were used for comparison with labeling of normal retina and RPE.
In pyogenic granuloma, there was intense labeling with anti-Iα5ß1 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. No anti-Iα5ß1 immunoreactivity (IR) was seen in normal retina and RPE. As for the study tissues, 8 membrane specimens from 6 patients (4 male/2 female) provided enough tissue for immunohistochemical analysis. All membranes were labeled distinctly with anti-CK18 and anti-CD68. All samples also revealed a consistent and prominent IR with the 3 antibodies to Iα5ß1. This IR co-localized mostly with cells that were also positive for CK18 and with some cells that were positive for CD68. No significant IR was seen with anti-Factor VIII in any of the membranes apart from a subtle staining of a few cells in the diabetic membrane. By contrast, the neovascular membrane within the enucleated eye showed intense labeling of all vascular channels with anti-Factor VIII as well as with anti-Iα5ß1.
In preretinal membranes, there is marked anti-Iα5ß1 IR in cells of most likely RPE and macrophage origin even when no vascular channels are evident. Iα5ß1 might therefore be an important target in future treatment of PVR.
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