Loss of Shp2-mediated mitogen-activated protein kinase signaling in Müller glial cells results in retinal degeneration

Zhigang Cai, David L. Simons, Xin Yuan Fu, Gen Sheng Feng, Samuel M. Wu, Xin Zhang

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Extensive studies have identified many growth factors and intracellular pathways that can promote neuronal survival after retinal injury, but the intrinsic survival mechanisms in the normal retina are poorly understood. Here we report that genetic ablation of Shp2 (Ptpn11) protein phosphatase resulted in progressive apoptosis of all retinal cell types. Loss of Shp2 specifically disrupted extracellular signal-regulated kinase (ERK) signaling in Müller cells, leading to Stat3 activation in photoreceptors. However, neither inactivation of Stat3 nor stimulation of AKT signaling could ameliorate the Shp2 retinal degeneration. Instead, constitutively activated Kras signaling not only rescued the retinal cell numbers in the Shp2 mutant but also functionally improved the electroretinogram recording (ERG). These results suggest that Shp2-mediated Ras-mitogen-activated protein kinase (Ras-MAPK) signaling plays a critical role in Müller cell maturation and function, which is necessary for the survival of retinal neurons.

Original languageEnglish (US)
Pages (from-to)2973-2983
Number of pages11
JournalMolecular and cellular biology
Volume31
Issue number14
DOIs
StatePublished - Jul 1 2011

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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