The incorporation of transplanted cells into the host retina is one of the prerequisites for successful cell replacement therapy to treat retinal degeneration. To test the hypothesis that injury promotes cell incorporation, stem cells/progenitors were isolated from the retina, ciliary epithelium or limbal epithelium and transplanted into the eyes of rats with retinal injury. Different stem cell/progenitor populations incorporated into traumatized or diseased retina but not into the normal retina. The proportion of cells incorporated into the inner retina was consistently higher than in the outer retina. The transplanted cells expressed markers specific to cells of the lamina into which they were incorporated suggesting that cues for specific differentiation are localized within the inner and outer retina. These findings demonstrate that injury-induced cues play a significant role in promoting the incorporation of ocular stem cells/progenitors regardless of their origin or their differentiation along specific retinal sublineage.
Evidence suggests that, as development ensues, the competence of neural progenitors is progressively altered, such that they become fated to give rise to neurons of a particular stage. Here, we demonstrate that late retinal progenitors can give rise to retinal ganglion cells (RGCs), an example of an early-born cell type in the retina. A subset of late retinal progenitors in vitro responds to cues that favor RGC differentiation by displaying markers characteristic of RGCs. In addition, mechanisms used during normal RGC differentiation are recruited by these cells toward their differentiation along RGC lineage. Our observations suggest that late neural progenitors may not be irreversibly fated but may appear as such under the constraints dictated by epigenetic cues.
These suggest that LPA can potently stimulate RPE cell proliferation via activation of a G-protein coupled receptor. LPA, which can be released by thrombin-activated platelets and growth factor-activated fibroblasts, might, therefore, play a role in the development of PVR.
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