Activated Neuroepithelial Progenitor Cells Are Present In The Vitreous Of Patients With Proliferative Vitreoretinopathy

Abstract

Purpose: : Proliferative vitreoretinopathy (PVR) is an important cause and complication of retinal diseases such as retinal detatchment. Fibrous membranes form and apply traction forces on the retina, causing it to detatch. It has not been fully elucidated how this process is initiated, but secretion of inflammatory substances and migration of mesenchymal, glial and inflammatory cells into the corpus vitreum are known to be contributing factors. We hypothesized that PVR activate neuroepithelial stem/progenitor cells from the ciliary margin at the periphery of the retina to migrate into the vitreous.

Methods: : Vitreous samples obtained after vitrectomy for PVR retinal detachments (n=24) were fixated directly after surgery or cultured in a stem cell-promoting medium for up to 3 passages. Cells were characterized with immuncytochemistry, RT-PCR, flow cytometry and electron microscopy.

Results: : Small sphere-like structures were observed in close vicinity to the ciliary margin during surgery. After isolation and culture of the vitreous, spheres formed in 16 out of 25 samples. These spheres showed a characteristic population of cell positive for neuroepithelial progenitor markers such as nestin, GFAP, Tuj1 and CD133, and displayed a mixed neural - and epithelial morphology. Importantly, vitreous samples that were fixed immediately after surgery also contained small sphere-like structures positive for neuroepithelial progenitor markers.

Conclusions: : Our results indicate that a population of immature neuroepithelial progenitor cells are activated to migrate into the vitreous of patients with PVR.

Keywords: proliferative vitreoretinopathy • ciliary body • retina