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X. Zhang, Z. Cai, D. Simons, G.-S. Feng, S. M. Wu; Shp2 Mediated Mapk Signaling in Müller Glial Cells Plays an Essential Role in Adult Retina Cell Survival. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6442.
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© ARVO (1962-2015); The Authors (2016-present)
Multiple growth factors such as FGF, BDNF, CNTF and GDNF have been implicated as neuroprotective factors for cell survival in the adult retina and other parts of the nervous system, but their downstream signaling pathways remained largely unclear. Our recent study has shown that the protein tyrosine phosphatase Shp2 mediates FGF-MAPK signaling to determine the retina neural fate versus the retina pigmented epithelium fate during early ocular development. Here, we investigated the functional requirement of Shp2 is adult retina cell survival
The Shp2 retinal specific knockout mutants are analyzed by histology and immunohistochemistry.
We report that, after retinal cells have differentiated, the Shp2-MAPK signaling axis is postnatally reactivated in Müller glial cells to promote adult retina cell survival. Late retina-specific depletion of Shp2 does not affect normal retina cell proliferation and differentiation but induces progressive apoptosis of all retina cell types at adult stages. Constitutively activated K-Ras, but not Stat3 or AKT, rescues the retinal defects in the Shp2 mutant both morphologically and functionally, while the loss of AKT or Stat3 signaling does not cause retinal degeneration in adult animals.
These studies suggest that, in the uninjured adult retina, MAPK signaling in Müller glial cells functions as the essential survival pathway in response to the intrinsic neuroprotective stimuli; and that the normal Müller glial cells are critical for the survival of other retinal cells.
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