Matrix and the retinal pigment epithelium in proliferative retinal disease

In their normal state, RPE cells are strongly adherent to Bruch's membrane. Certain pathological conditions such as retinal detachment cause an injury -type response (probably augmented or induced by the local accumulation of a variety of substances which modulate cell behaviour) in which RPE begin t o dissociate from the membrane. This RPE Bruch's membrane separation may be mediated by proteins with counter-adhesive properties and proteolytic enzy mes, partly derived from the RPE themselves. Concomitant with the RPE disas sociation, the cells begin to lose tertiary differentiation characteristics and gain macrophage-like features. When the "free" RPE arrive at the surface of the neuroretina, they may atta ch to or create a provisional matrix. Some of the cells adopt a fibroblast- like phenotype. This phenotype is similar to that of the dermal fibroblast during cutaneous wound repair and the fibroblastic RPE synthesise the types of matrix components found in healing skin wounds. Many of these molecules in turn further modulate the activities of the cells via several families of cell surface receptors, while the RPE continue to remodel the new matrix with a range of proteolytic enzymes. The resulting tissue (or membrane) ha s many of the features of a contractile scar and is the hallmark of the con dition known as proliferative vitreoretinopathy (PVR). Thus the development of PVR, and the resulting tractional distortion of the neuroretina, appear s to be dependent on RPE-matrix interactions. The interactions present a nu mber of potential therapeutic targets for the management of the disorder. ( C) 1998 Elsevier Science Ltd. All rights reserved.