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K. Lashkari, T. Ng, M. Shatos, T. Hirose; NMDA Modulates Migration Behavior of Neuronal Progenitor (PFV) Cells Collected From Eyes With Persistent Fetal Vasculature. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3575. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate differentiation and migration patterns of transplanted progenitor cells derived from persistent fetal vasculature (PFV) with or without NMDA ablation of retinal ganglion cells in the host eye.
PFV cells have been previously shown to differentiate into mature neuronal elements that exhibit characteristics that are similar to retinal ganglion cells. PFV, fibroblasts or P0 murine retinal progenitor cells were pre-labeled with either PKH26 tagged rhodamine or AAV-GFP and injected into the vitreous of C57BL/6 mice. Mice were pretreated with either PBS or NMDA (N-methyl-D-Aspartic acid), which is toxic to retinal ganglion cells. Animals were sacrificed at 3-28 days and were subjected to frozen sectioning and immunohistochemistry for expression of differentiation markers, neurofilament-200, growth-associated protein (GAP-43), PKC-α, GFAP and nestin.
Transplanted PFV cells differentiated into neuronal cells and survived all time points. In absence of NMDA, cells developed newly formed GAP-43+ fibers that penetrated the host optic disc to the lamina cribrosa. In response to NMDA ablation of retinal ganglion cells, PFV cells developed sheaths of differentiated neuronal cells that adhered to the inner retina in lieu of direct optic disc migration. Fibroblasts non-specifically bound to the inner retina resulting in fixed retinal folds and failed to penetrate the optic disc. P0 mouse retinal progenitors cells failed to penetrate the optic disc or adhere to the retina.
Only PFV and not fibroblasts or P0 mouse retinal progenitor cells could selectively migrate and penetrate the host optic disc. This migration behavior is modulated by presence of host’s intact ganglion cell fibers since selective ablation of retinal ganglion cells changes the path of migration toward the inner retina. Data suggest that optic nerve head of the host releases the principal chemoattractant that controls PFV cells migration and penetration.
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