Characterization of putative retinal stem cells in the adult human eye

In lower vertebrates, retinal injury is known to activate neural stem cells (NSCs) in the ciliary marginal zone (CMZ). Cells expressing markers of NSCs are also present in the ciliary body epithelium (CE) and in Müller glia in the peripheral retina (PR) of the human eye. However, these cells seem to be quiescent in the adult human. We tested whether NSC-like cells could be activated in eyes with proliferative vitreoretinopathy (PVR). The PR and CE were studied for NSC-associated markers in human enucleated control eyes and eyes with confirmed PVR. Furthermore, cells isolated from vitreous samples obtained during vitrectomies for retinal detachment were directly fixed or cultured and compared to cells cultured from the post mortem retina and CE. In situ characterization of the normal eyes revealed robust expression of markers present in NSCs only around peripheral cysts of the proximal pars plana region and the PR. Although there were higher numbers of dividing cells in the CE of PVR eyes than in controls, we did not detect of NSC-associated markers in the CE. In PVR eyes, proliferation of both non-glial and glial cells co-staining NSC-associated markers was evident around the ora serrata region. Spheres formed in vitreous samples from patients with PVR and expressed glial - and NSC-associated markers. In conclusion, the adult human eye may harbor two different populations of neuroepithelial stem/progenitor cells, a non-glial and a Müller glial-like population. Yet, only the glial population responded to retinal injury by targeted migration into the vitreous.