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F. J. Adamakos, S. Maloney, E. Antecka, B. F. Fernandes, E. Castiglione, M. N. Burnier, Jr.; Expression of PAR-1, PAR-3 and PAR-4 in Human Choroidal Neovascular Membranes. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3409.
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Protease-activated receptors (PARs) have been shown to promote disease progression in cancer by playing critical roles in angiogenesis. Accordingly, PARs may promote abnormal non-neoplastic neovascularization such as in patients with Age-related Macular Degeneration (AMD). The aim of this study was to investigate expression of PARs in choroidal neovascular membranes (CNV) excised from patients with neovascular AMD.
Formalin-fixed, paraffin-embedded sections of CNV membranes surgically excised from 8 patients with AMD were immunostained for PAR-1, PAR-3 and PAR-4 expression, using the Ventana BenchMark fully automated machine. Staining was evaluated by a trained ocular pathologist and classified as either negative or positive in each of the following cell types: retinal pigment epithelial cells (RPE), vascular endothelial cells and fibroblasts. Two control eyes from patients with no history of AMD were obtained from the eye bank and were also stained.
Five of 8 (63%) CNV membranes stained positive for PAR-1 in RPE cells and 6 of 8 (75%) stained positive in vascular endothelial cells. Only 2 of 8 (25%) stained positive for PAR-1 in fibroblasts. All CNV membranes stained positive for PAR-3 in RPE cells, while 7 of 8 (89%) stained positive in vascular endothelial cells and 5 of 8 (63%) stained positive in fibroblasts. None of the CNV membranes stained for PAR-4 in RPE cells, while 2 of 8 (25%) stained positive for PAR-4 in vascular endothelial cells and 5 of 8 (63%) stained positive in fibroblasts. Control eyes stained positive in the RPE and the choroid for all three receptors.
We observed different expression of each PAR in AMD-related CNVs. Most notably, PAR-4 expression was absent in RPE cells in all membranes yet positive in the RPE of control eyes. It is possible that the loss of PAR-4 expression in RPE cells plays an important role in the development of CNV in AMD patients. Further investigation is warranted to elucidate the significance of this finding.
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