Periostin in the Pathogenesis of Proliferative Vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment and vitreoretinal surgery. The hallmark of PVR is the formation of subretinal and epiretinal fibrotic membranes that can lead to traction retinal detachment due to their contractile properties. Surgical removal of the fibrotic membranes and retinal detachment repair are the first choice treatments for PVR. Despite recent progress in surgical techniques, recurrent detachment can lead to irreversible damage and a poor prognosis for visual acuity. Therefore, it is important to develop new molecular targeting therapies based on the exact pathogenesis of PVR. In order to determine the genes responsible for development of PVR, we performed gene expression profiling of fibrous membranes excised from PVR patients using DNA microarray analysis. This analysis revealed significant up-regulation of periostin. We also found increased periostin expression in the vitreous and retinal pigment epithelial (RPE) cells in fibrous membranes of PVR patients. In vitro, periostin increased proliferation, adhesion, migration and collagen production in primary human RPE cells through integrin αV-mediated FAK and AKT phosphorylation. Blockade of periostin suppressed migration and adhesion induced by TGF-β2 and PVR vitreous. In vivo, periostin inhibition had the inhibitory effect on progression of experimental PVR in rabbit eyes without affecting the viability of retinal cells. These results identified the novel causal link between periostin and the generation of PVR membranes as well as a promising therapeutic target for PVR.