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G. Chen, M. A. Shatos, K. Lashkari; Neuronal Progenitor Cells Derived From Human Persistent Fetal Vasculature Are Good Candidate Cells for Optic Nerve Transplantation. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3149.
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© ARVO (1962-2015); The Authors (2016-present)
Persistent fetal vasculature (PFV) is caused by failure of the primary vitreous and the hyaloidal vascular systems to regress during development. Our laboratory has previously shown that PFV membranes are potential sources of progenitor cells. We have characterized these cells in vitro and evaluated their potential use in optic nerve transplantation.
PFV cells were subjected to IHC and qRT-PCR analysis for expression of progenitors and neuronal markers, and gene expression. Calcium imaging was also performed to evaluate the response profiles to different neurotransmitters. Results were compared with human retinal progenitor cells (hRPC). For transplantation, PFVs were labeled with AAV2-GFP and intravitreally injected into DBA/2J pigmentary glaucoma mice. Mice were sacrificed at 30 days and confocal microscopy was performed.
Cultured PFV cells highly express neural progenitor (Nestin, Ki67, Brn3a, and MAP1b) and adult neuronal (beta-tubulinIII, NF200 and Thy1) markers. 25% of cultured PFV cells uptake Brdu and have a stem-cell like morphlogy. Compared to hRPCs, PFVc express higher copies of synapse-related genes transcripts (SNAP25, NLGN4Y, STXBP1 and RAPSN). Calcium imaging revealed the following responses: glutamate 75%, glycine 38%, GABA 33%, acetylcholine 26%, and dopamine 19%). Following tranplantation, PFVs migrated into the inner retina and intraorbital portion of optic nerve.
PFV cells express progenitor and adult neuronal markers and morphology simlar to retinal ganglion cells. Intravitreal transplantation of PFV cells into glaucomatous mice results in their migration and incorporation into sites of retinal ganglion cell damage. These cells may be good candidates for cell-based therapy for glaucomatous and other optic nerve damage.
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