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P Hermans, A Lommatzsch, G Spital, S Woijtecki, D Mueller, N Bornfeld, D Pauleikhoff; RPE Integrins And Extracellular Matrix Proteins In Normal Macula And Exudative AMD . Invest. Ophthalmol. Vis. Sci. 2002;43(13):695.
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Purpose: The normal adhesion of the RPE with Bruch´s Membrane (BM) is promoted by integrins and extracellular matrix (ECM) proteins. Because changes in the composition of the RPE ECM and the expression of specific integrins may be an important factor associated with the developement of exudative AMD lesions, the aims of the study was the analysis of ECM proteins and RPE integrins in the RPE of macula of elderly donors and in the RPE of different exudative AMD lesions. Methods: Macular specimens of 25 donor eyes (≷65y) and 20 surgically excised exudative AMD lesions (CNV and vascul. PED) were examined by immunhistochemistry. Cryo sections were stained for integrins alpha 2-6 and V, beta 1,2 and the heterodimers alpha5beta1, alphaVbeta3, alphaVbeta5 as well as for the ECM proteins laminin, collagen IV, fibronectin and vitronectin. Staining was qualitatively classified as positive or negative. Results: In the RPE ECM of macular specimens of donors ≷65y positive continiuos staining could only be observed for vitronectin (100% pos. staining) while laminin, collagen IV and fibronectin showed staining only in 20%,30% and 10%. The integrin pattern demonstrated weak positive staining for all subunits and heterodimers with the exception of alpha 2 and 4. This integrin staining pattern could also be seen but more continious at the basal surface of the RPE in exudative AMD lesions. In these lesions the RPE and associated sub-RPE ECM deposits (BLD) showed positive staining for laminin, vitronectin, fibronectin (all 100% pos.)and collagen IV (70%pos.). Conclusion: In older macular specimens the RPE ECM-proteins and integrin pattern could not be demonstrated continiuos perhaps due to aging changes like protein crosslinking. This process may result in regressed adhesive properties of the RPE cells. In contrast in exudative AMD lesions a continious positive staining for all integrins could be seen as well as a strong positive staining for the ECM proteins studied in the basal ECM of the RPE cells. This could be interpreted as a stimulated metabolic activity of RPE ECM production in exudative AMD lesions with increased integrin receptor expression, newly produced laminin in the basal ECM and excessive vitronectin and fibronectin production and deposition in BLD, which was always associated with the development of choroidal neovascularisation.
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