Induction of arachidonic acid metabolite release by human fibroblasts in proliferative vitreoretinopathy

Abstract

Proliferative vitreoretinopathy is a severe ocular disorder characterized by unwanted proliferation of cells and excessive production of fibrous tissue, which leads to the formation of cellular membranes on the surface of the retina and in the vitreous. Proliferative vitreoretinopathy is the most common cause of failure in retinal reattachment surgery, approximately occurring in one out of ten operated eyes. Proliferation of retinal pigment epithelial cells and fibroblasts is a cornerstone in the pathogenesis of proliferative vitreoretinopathy. An in vitro-proliferation assay showed previously that intraocular fluid from patients with proliferative vitreoretinopathy is potently effective in stimulating proliferation of human fibroblasts. Here we show that exposure of human fibroblasts to vitreous fluids from patients with proliferative vitreoretinopathy causes a rapid and sustained increase in arachidonic acid metabolite release as measured by competitive enzyme-immunoassay. The findings implicate prostaglandin E2 as a contributor to enhanced intraocular fibrosis in proliferative vitreoretinopathy. As prostaglandin E2 is a mediator of continuous aqueous-blood retinal barrier breakdown in this severe disease, cycclooxygenase inhibitors such as acetylsalicylic acid, which was successfully used in this study for blocking the effect of intraocular fluid, may be useful agents in targeting the progression of intraocular fibrosis.