Involvement of tdTomato-Tagged RPE cells in a mouse PVR model with enzymatically compromised retina.

Abstract

Ocular trauma and surgery are considered the most common cause for proliferative vitreoretinopathy (PVR). Many retinal cell types are thought to be the cellular source for PVR although most risk factors for PVR are associated with intravitreal dispersion of the retinal pigment epithelium (RPE) cells. Major PVR animal models are rabbit and swine with an artificial implantation of exogenous cells into the vitreous to form epiretinal membrane (ERM) which does not recapitulate a real PVR pathology. To clarify and validate the participation of RPE cells, to mimic ocular trauma in situ, and to reveal the related macromolecule changes in PVR pathology, we utilized a dispase treatment to damage the retina in establishment of a reliable RPE-tagged PVR mouse model with ERM-like tissues formed within and on both surface of the retina. The immunostaining of patient epiretinal membranes with lineage markers confirms RPE is involved in PVR development. Quantitative PCR analysis indicates the dedifferentiation of RPE cells switches RPE from epithelial to mesenchymal phenotype to re-enter a proliferative and mobile state underlying PVR. Gene expression results of the mouse PVR model retinas are consistent with the microarray gene expression profile of human PVR retinas, validating that our mouse PVR model resembles human PVR and is thereby suitable for molecular mechanism and pharmaceutical studies.