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- Title
Myofibroblasts in proliferative diabetic retinopathy can originate from infiltrating fibrocytes and through endothelial-to-mesenchymal transition (Endo MT).
- Authors
Abu El Asrar, A.; De Hertogh, G.; van den Eynde, K.; Alam, K.; Van Raemdonck, K.; Opdenakker, G.; Van Damme, J.; Geboes, K.; Struyf, S.
- Abstract
Purpose The fibrovascular epiretinal membranes from patients with proliferative diabetic retinopathy ( PDR) are characterized by the accumulation of a large number of myofibroblasts. We explored the hypothesis that proliferating endothelial cells via endothelial-to-mesenchymal transition (Endo MT) and/or bone marrow-derived circulating fibrocytes contribute to the myofibroblast population present in PDR membranes. Methods Epiretinal membranes from 14 patients with PDR were studied by immunohistochemistry. In addition, we investigated the phenotypic changes that take place in human retinal microvascular endothelial cells following exposure to transforming growth factor-β ( TGF-β1), connective tissue growth factor ( CTGF) and the proinflammatory cytokines interleukin-1β ( IL-1β) and tumor necrosis factor-a ( TNF-a). Results All membranes contained neovessels expressing the endothelial cell marker CD31. CD31+ endothelial cells co-expressed the fibroblast/myofibroblast markers fibroblast-specific protein-1 ( FSP-1) and a- SMA, indicative for the occurrence of endo MT. In the stroma, cells expressing FSP-1, a- SMA, the leukocyte common antigen CD45, and the myelomonocytic marker CD11b were detected. Double labeling showed co-localization of CD45 with FSP-1 and a- SMA and co-localization of CD11b with a- SMA and matrix metalloproteinase-9, demonstrating the presence of infiltrating fibrocytes. Retinal microvascular endothelial cells changed morphology upon cytokine exposure, lost the expression of endothelial cell markers (endothelial nitric oxide synthase and vascular endothelial-cadherin) and started to express mesenchymal markers (calponin, snail, transgelin and FSP-1). Conclusions These results suggest that endothelial cells as well as circulating fibrocytes may differentiate into myofibroblasts in the diabetic eye and contribute to pathologic fibrosis in PDR.
- Subjects
MYOFIBROBLASTS; RETROLENTAL fibroplasia; DIABETIC retinopathy; BLINDNESS; FIBROBLASTS
- Publication
Acta Ophthalmologica (1755375X), 2015, Vol 93, pn/a
- ISSN
1755-375X
- Publication type
Abstract
- DOI
10.1111/j.1755-3768.2015.1290