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 Citations (Scopus)

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
Pages (from-to)2973-2983
Number of pages11
JournalMolecular and Cellular Biology
Volume31
Issue number14
DOIs
StatePublished - Jul 2011

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Retinal Degeneration
Mitogen-Activated Protein Kinases
Neuroglia
Retinal Neurons
Phosphoprotein Phosphatases
Extracellular Signal-Regulated MAP Kinases
Retina
Intercellular Signaling Peptides and Proteins
Cell Count
Apoptosis
Wounds and Injuries

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Loss of Shp2-mediated mitogen-activated protein kinase signaling in Müller glial cells results in retinal degeneration. / Cai, Zhigang; Simons, David L.; Fu, Xin Yuan; Feng, Gen Sheng; Wu, Samuel M.; Zhang, Xin.

In: Molecular and Cellular Biology, Vol. 31, No. 14, 07.2011, p. 2973-2983.

Research output: Contribution to journalArticle

Cai, Zhigang ; Simons, David L. ; Fu, Xin Yuan ; Feng, Gen Sheng ; Wu, Samuel M. ; Zhang, Xin. / Loss of Shp2-mediated mitogen-activated protein kinase signaling in Müller glial cells results in retinal degeneration. In: Molecular and Cellular Biology. 2011 ; Vol. 31, No. 14. pp. 2973-2983.
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