Characterization of neuroepithelial progenitor cells in patients with proliferative vitreoretinopathy

Abstract

AbstractPurpose Proliferative vitreoretinopathy (PVR) is an important cause of retinal diseases such as retinal detachment (RD). In lower vertebrates, retinal damage is known to activate neuroepithelial stem cells (NSCs) in the ciliary margin in an attempt to regenerate the neuroretina. Cells expressing some markers of NSCs are also present in the retina and the ciliary body epithelium (CB) of the adult human eye. We hypothesized that if NSCs exist in the adult human eye, they should be activated by PVR formation.Methods Cells isolated from vitreous samples (n=25) obtained during vitrectomies for RD were directly fixed or cultured in a stem cell‐promoting medium, and compared to cells isolated from post mortem CB and peripheral retina (PR) using sphere‐forming assay, immunohistochemistry, molecular biology and electron microscopy. Markers of NSCs were also studied in whole retinal control/PVR sections obtained from enucleations.Results Spheres formed in 7/10 vitreous samples from patients with PVR compared to 2/15 samples from patients with no known PVR. These spheres stained for markers of NSCs both in vivo and after repetitive passages. Their mRNA and immunohistochemical profile resembled sphere‐forming cells from the PR with only a few characteristics of CB cells. In situ characterization of the CB revealed that although there were higher numbers of dividing cells in PVR eyes than in controls, we did not detect markers of NSCs. Interestingly, markers of NSCs were evident around PR cysts with some evidence of activation following PVR formation.Conclusion A population of NSC‐like cells are found in the vitreous of patients with PVR. These cells seem to be originated from the retina itself and not the CB.