Matrix metalloproteinases - A role in the contraction of vitreo-retinal scar tissue

The most common cause of failure of retinal reattachment surgery is formati on of fibrocellular contractile membranes on both surfaces of the neuroreti na. This intraocular fibrosis, known as proliferative vitreoretinopathy, re sults in a blinding tractional retinal detachment because of the contractil e nature of the membrane. Contractility is a cell-mediated event that is th ought to be dependent on locomotion and adhesion to the extracellular matri x. Interactions between cells and the extracellular matrix can be influence d by matrix metalloproteinases (MMPs) and we investigated the role of MMPs in two in vitro models (two-and three-dimensional) of human retinal pigment epithelial (RPE) cell-mediated contraction. MMP activity was detected usin g enzyme-linked immunosorbent assays and zymography techniques that reveale d MMP-1, -2, -3, and -9 positivity during the collagen matrix contraction a ssays. RPE-populated collagen matrix contraction (three-dimensional) was in hibited using a cocktail of anti-MMP antibodies and with Ga-lardin (a broad -spectrum MMP inhibitor). Galardin inhibition was dose-dependent, reversibl e, and dependent on cell number. MMP inhibitors had no effect on contractio n when RPEs were seeded on two-dimensional collagen matrices or on cellular adhesion to collagen type I. Our results suggest that MMP activity may be required for three-dimensional but not two-dimensional RPE-collagen matrix contraction.