Genesis of Retinal Ganglion Cells by Targeted Expression of
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Retinal ganglion cell (RGC) degeneration is a hallmark of glaucoma, the most prevalent cause of irreversible blindness. Thus, therapeutic strategies are needed to protect and replace these projection neurons. One innovative approach is to promote genesis of RGCs via manipulation of endogenous cell sources. Here, we demonstrate that the pluripotency regulator gene Krüppel-like factor 4 () is sufficient to change the potency of lineage-restricted retinal progenitor cells to generate RGCs Transcriptome analysis disclosed that the overexpression of induces crucial regulators of RGC competence and specification, including and In contrast, loss-of-function studies in mice and zebrafish demonstrated that is not essential for generation or differentiation of RGCs during retinogenesis. Nevertheless, induced RGCs (iRGCs) generated upon overexpression migrate to the proper layer and project axons aligned with endogenous fascicles that reach the optic nerve head. Notably, iRGCs survive for up to 30 days after generation. We identified as a promising candidate for reprogramming retinal cells and regenerating RGCs in the retina.This article has an associated 'The people behind the papers' interview.
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