title: Retinal Pigment Epithelium and Müller Progenitor Cell Interaction Increase Müller Progenitor Cell Expression of PDGFRα and Ability to Induce Proliferative Vitreoretinopathy in a Rabbit Model.
abstract: Purpose. Proliferative vitreoretinopathy (PVR) is a complication of retinal detachment characterized by redetachment of the retina as a result of membrane formation and contraction. A variety of retinal cells, including retinal pigment epithelial (RPE) and Müller glia, and growth factors may be responsible. Platelet-derived growth factor receptor alpha (PDGFRα) is found in large quantities in PVR membranes, and is intrinsic to the development of PVR in rabbit models. This study explores the expression of PDGFR in cocultures of RPE and Müller cells over time to examine how these two cell types may collaborate in the development of PVR. We also examine how changes in PDGFRα expression alter Müller cell pathogenicity. Methods. Human MIO-M1 Müller progenitor (MPC) and ARPE19 cells were studied in a transmembrane coculture system. Immunocytochemistry and Western blot were used to look at PDGFRα, PDGFRβ, and GFAP expression. A transfected MPC line cell line expressing the PDGFRα (MIO-M1α) was generated, and tested in a rabbit model for its ability to induce PVR. Results. The expression of PDGFRα and PDGFRβ was upregulated in MIO-M1 MPCs cocultured with ARPE19 cells; GFAP was slightly decreased. Increased expression of PDGFRα in the MIO-M1 cell line resulted in increased pathogenicity and enhanced ability to induce PVR in a rabbit model. Conclusions. Müller and RPE cell interaction can lead to upregulation of PDGFRα and increased Müller cell pathogenicity. Müller cells may play a more active role than previously thought in the development of PVR membranes, particularly when stimulated by an RPE-cell-rich environment. Additional studies of human samples and in animal models are warranted.
authors.affiliation: Department of Ophthalmology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Gisela
authors.initials: G
authors.lastname: Velez
authors.forename: Alexa R
authors.initials: AR
authors.lastname: Weingarden
authors.forename: Budd A
authors.initials: BA
authors.lastname: Tucker
authors.forename: Hetian
authors.initials: H
authors.lastname: Lei
authors.forename: Andrius
authors.initials: A
authors.lastname: Kazlauskas
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Young