TGF-beta 1, TGF-beta receptor II and ED-A fibronectin expression in myofibroblast of vitreoretinopathy

PURPOSE. Formation of scarlike epiretinal membranes (ERMs) constitutes pote ntially the end stage of evolution of proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Among various cellular popul ations, ERMs contain cells with contractile features typical of myofibrobla sts. The current study was conducted to investigate the presence of transfo rming growth factor (TGF)-beta 1, TGF-beta receptor II (RII) and ED-A fibro nectin (FN), the main inducers of myofibroblastic differentiation in ERMs i n PDR and PVR. METHODS. Samples of ERM were obtained from 23 patients during microsurgery for PVR or PDR. Electron microscopy, immunohistochemistry, and confocal mic roscopy with antibodies recognizing alpha-smooth muscle (SM) actin, desmin, TGF-beta 1, TGF-beta receptors I and II, and ED-A FN were performed. RESULTS. alpha-SM actin was detected in all ERMs, whereas desmin was presen t in 50% of the cases; ED-A FN was expressed in all ERMs in close relation with alpha-SM actin-positive myofibroblasts. In addition, TGF-beta 1 and TG F-beta R II were always present, TGF-beta RII being expressed in both alpha -SM actin-positive and negative fibroblastic cells. CONCLUSIONS. Myofibroblast accumulation is a key event in ERM-associated tr action retinal detachment occurring during PVR and PDR. The current results suggest that the presence of alpha-SM actin-positive myofibroblasts is pro bably dependent on the concomitant neoexpression of TGF-beta 1, TGF-beta RI I, and ED-A FN. The results furnish new data on the mechanism of alpha-SM a ctin stimulation in fibroblasts in a human pathologic setting.