Abstract
Abstract: :
Purpose: Endothelin–1 (ET–1) is a small peptide that modulates survival and growth of different cell types, including glial cells. It also regulates production of extracellular matrix and has been associated to pathological fibrosis. In previous studies we detected the presence of ET–1 expression in myofibroblasts from human proliferative vitreoretinopathy (PVR) membranes. We have now asked whether a similar co–localization was present in PVR–like membranes experimentally induced in mice. Methods: Human specimens were obtained from patients undergoing surgery for PVR (according to World Medical Association rules). Experimental retinal detachment and PVR–like lesions were induced in C57Bl/6 mice using intravitreal injections of dispase–collagenase (Roche Applied Science). Samples were proccessed for immunohistochemistry and confocal microscopy using primary antibodies for ET–1 and smooth muscle actin (SMA). Results: Experimentally induced membranes contained numerous SMA+ elongate cells. Co–localization with ET–1 immunoreactivity could be detected using confocal microscopy. No SMA immunoreactivity was present in the neural retina, even after dispase treatment. By contrast, ET–1 immunoreactivity was present in astrocytes. After dispase injection, endothelinergic astrocytes showed an increase in number and length of their processes. Elongate cells showing ET–1 immunoreactivity appeared along the interface between neural retina and epiretinal membrane. Some of these cells resembled myofibroblasts. A similar distribution of ET–1 and SMA immunoreactivity was found in human PVR membranes. Conclusions: The presence of ET–1 in myofibroblasts suggests a role of this peptide in migration and contraction of these cells. De novo expression of ET–1 gene has been demonstrated in myofibroblasts from other sources. However, a transition of retinal astrocytes into myofibroblasts might occur during PVR membrane development.
Keywords: proliferative vitreoretinopathy • retina • vitreoretinal surgery