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Shp-2 regulates the TrkB receptor activity in the retinal ganglion cells under glaucomatous stress

Vivek K Gupta1, Yuyi You, Alexander Klistorner

  • 1Australian School of Advanced Medicine, Macquarie University, Australia. vivek.gupta@mq.edu.au

Biochimica Et Biophysica Acta
|August 11, 2012
PubMed

Insights

SH2 domain-containing phosphatase-2 (Shp-2) binds to the Tropomyosin-receptor-kinase B (TrkB) receptor in retinal ganglion cells (RGCs), inhibiting its activity. This Shp-2 mediated deactivation of TrkB contributes to RGC degeneration in glaucoma.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Ophthalmology

Background:

  • Tropomyosin-receptor-kinase B (TrkB) receptor activation is crucial for retinal ganglion cell (RGC) survival.
  • Glaucomatous stress leads to RGC degeneration, a process not fully understood at the molecular level.

Purpose of the Study:

  • To investigate the role of SH2 domain-containing phosphatase-2 (Shp-2) in regulating TrkB receptor activity in RGCs under glaucomatous stress.
  • To elucidate the molecular mechanisms underlying Shp-2 mediated TrkB deactivation and its contribution to RGC loss in glaucoma.

Main Methods:

  • Investigated the interaction between Shp-2 and TrkB receptor in RGCs using biochemical assays.
  • Examined the role of caveolin in mediating the binding of Shp-2 to TrkB.
  • Assessed Shp-2 activation and TrkB activity in RGCs under in vivo glaucomatous stress conditions.
  • Evaluated the effect of Shp-2 inhibition on TrkB activity in cells exposed to excitotoxic and oxidative stress.

Main Results:

  • SH2 domain-containing phosphatase-2 (Shp-2) binds to the TrkB receptor in RGCs, negatively regulating its activity under glaucomatous stress.
  • Caveolin 1 and 3 are hyper-phosphorylated and bind to Shp-2, facilitating TrkB-Shp-2 interaction.
  • Shp-2 activation and TrkB deactivation occur concurrently with RGC degeneration in vivo under glaucomatous stress.
  • Inhibition of Shp-2 restored TrkB activity in RGCs subjected to excitotoxic and oxidative stress.

Conclusions:

  • Shp-2 acts as a negative regulator of TrkB receptor activity in RGCs.
  • The caveolin-mediated interaction between Shp-2 and TrkB contributes to RGC degeneration in glaucoma.
  • Targeting Shp-2 may offer a therapeutic strategy to preserve RGCs in glaucoma.

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