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Ray Gariano, Luo L. Zheng; Endothelial Mesenchymal Transition in Human Diabetic Epiretinal Fibrosis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5774.
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Epiretinal fibrosis is a leading cause of permanent blindness in patients with advanced diabetic retinopathy. The source of the fibroblasts within epiretinal fibrosis is uncertain. Recently, vascular endothelial cells have been shown to differentiate into fibroblasts, in a process termed Endothelial Mesenchymal Transition, or EndMT. This study aims to detect evidence of EndMT in diabetic retinopathy.
Epiretinal fibrovascular membranes were removed from patients undergoing vitrectomy surgery for diabetic traction retinal detachments. Membranes were fixed in formalin. Whole-mount double labeling fluorescence immunohistochemistry was performed using markers of vascular endothelium (CD31, Ulex lectin) and of fibroblasts (FSP1).
Four membranes from four patients were examined. In each case numerous FSP+ cells and CD31+ or Ulex+ vascular structures were evident. In all membranes spindle shaped double-labeled cells were found, separate from blood vessels. Double-labeled cells were detected infrequently and comprised a small minority of single-labeled cells.
The presence of FSP+/CD31+ double-labeled cells in diabetic epiretinal membranes indicates that fibroblasts in advanced retinopathy may arise via EndMT. The technique used in our study captures only those cells in earlier stages of transition, and may underestimate the total contribution of EndMT to the fibroblast population. A large fraction of fibroblasts arise via EndMT in several fibrosing diseases, including diabetic nephropathy and cardiomyopathy; EndMT.thus appears to be a pathologic mechanism common to multiple diabetic complications.
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