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Levi Todd, Andrew J Fischer; Hedgehog-signaling stimulates the formation of Müller glia-derived retinal progenitors. Invest. Ophthalmol. Vis. Sci. 2014;55(13):830.
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Müller glia can be stimulated to de-diferentiate, proliferate and form Muller glia-derived progenitor cells (MGPCs) that can regenerate retinal neurons. The identitiy of the pathways that regulate the de-differention of mature Müller glia and proliferation of MGPCs remain largely unknown. Hh-signaling is known to influence the proliferation of neural progenitors and astrocytes in the developing and mature nervous system. Thus, the purpose of this study was to investigate whether Hh-signaling influences the formation of MGPCs in the chick retina in vivo.
Immunocytochemistry was used to study Shh expression in mature and damaged chick retinas. The Hh-signaling inhibitor KAAD-cyclopamine or recombinant human Shh (rhShh) were injected into the vitreous chamber of normal and damaged eyes. Retinas were processed for cell proliferation, and glial reactivity. qRT-PCR was used to measure retinal levels of different Hh-related genes, cytokines and progenitor genes. Retinal damage was induced by an intraocular injection of N-Methyl-D-aspartate (NMDA).
Data is provided that Hh-signaling is active in mature intact retinas, influencing glial reactivity, and Hh-signaling is dramatically increased in damaged retinas. rhShh stimulates the formation of MGPCs in damaged retinas, but not in undamaged retinas. Conversely, inhibition of Hh-signaling with KAAD-cyclopamine reduces numbers of proliferating MGPCs in damaged retinas.
This work implicates Hh-signaling as a key regulator of the formation and proliferation of MGPCs.
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