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Ray Gariano, Anne M Hanneken, ; Fibroblasts in Diabetic Traction Retinal Detachment May Arise From Vascular Endothelial and Perivascular Cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4283.
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© ARVO (1962-2015); The Authors (2016-present)
Tractional retinal detachment is a surgically challenging and often blinding complication of severe diabetic retinopathy. Fibroblasts and myofibroblasts (FB) are a major cellular component of fibrotic tissues and the primary source of fibrotic matrix and contractility. The origin of FBs in diabetic retinopathy, however, is unknown. We evaluate the hypothesis that FBs arise from cells of the blood vessel wall.
Fluorescence immunohistochemistry for markers of FBs (FSP1), endothelial cells (CD31, vWF), pericytes (NG2), myeloid cells (CD68), and astrocytes (GFAP), was performed on flat-mounted diabetic and non-diabetic cadaveric retina, and on fibrovascular tissues removed from diabetic patients during surgery for traction retinal detachment.
In diabetic retina, occasional CD31+ endothelial cells and NG2+ pericytes were found adjacent to but separate from blood vessels. In fibrovascular specimens, FSP1+ cells were numerous and exhibited an ovoid or stellate morphology with one or more fine processes, typical of FBs. A small proportion of FBs exhibited CD31 immunoreactivity, consistent with an endothelial-mesenchymal transition giving rise to FBs. Similarly, FSP1+/NG2+ double-labeled cells were detected in fibrovascular specimens, suggestive of a pericyte source for FBs. In some cases, NG2+ pericytes exhibited FSP1 immunoreactivity while partly unwrapping from neovessels and migrating into the fibrotic stroma. Astrocytes (GFAP+) and myleoid cells (CD68+) were infrequently found in specimens, and only very rarely exhibited FSP1 labeling.
Endothelial and perivascular cells can detach from the vessel wall and “transition” to a fibroblast phenotype. Transitioning cells may retain vascular markers as they acquire fibroblast markers; such double-labeled cells occur in renal, pulmonary, cardiac, and hepatic fibrotic diseases and may comprise the majority of disease-related FBs. Our results suggest that these processes of separation and migration from the vessel wall and acquisition of a fibroblast phenotype also operate in the retina of patients with diabetic retinopathy. The transition of endothelial and perivascular cells to FBs is consistent with the tendency for diabetic preretinal fibrosis to localize along retinal vessels, and might exacerbate pericyte loss and vascular rarefaction, hallmarks of diabetic retinopathy.
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