Inventors: Prof Ayala Pollack and Dr Zeev Dvashi
Background: Proliferative vitreoretinopathy (PVR) is a scarring process that develops as complication during retinal detachments (RDs) and it is the most common cause of surgical failure upon RD treatment. PVR is a dynamic process characterized by the formation of fibrotic tissue on the detached retina, preventing the reattachment of the retina and finally may cause blindness. Retinal pigment epithelium (RPE) cells are the main factor that controls the development of the fibrotic tissue during PVR. RPE cells are quiescent and differentiated cells, however upon RD and the break of the blood-retina barrier, RPE cells are exposed to a variety of cytokines and growth factors found in the serum. Upon this exposure the RPE cells undergo epithelial-mesenchymal transition (EMT) demonstrating enhance expression of a–smooth muscle actin, secrete chemokines and cytokines, increase motility and produce extracellular matrix components participating in the fibrotic tissue formation on the detached retina.
We show hereby that transforming growth factor beta-activated kinase 1 (TAK-1) acts as a critical player in the regulation of RPE cells epithelial-mesenchymal transition, regulating this process and subsequently involved in maintain the naïve form of the cells.
Technology: A novel therapeutic modality to reduce PVR complication by halting the process of RPE cells transdifferentiation utilizing a TAK1 inhibitor.