April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Neuroprotective Effect of Up-regulated Sonic Hedgehog in Retinal Ganglion Cells Following Chronic Ocular Hypertension
Author Affiliations & Notes
  • J. Wu
    Eye & ENT Hospital, Fudan University, Shanghai, China
  • S. Zhang
    Eye & ENT Hospital, Fudan University, Shanghai, China
  • X. Sun
    Eye & ENT Hospital, Fudan University, Shanghai, China
  • Footnotes
    Commercial Relationships  J. Wu, None; S. Zhang, None; X. Sun, None.
  • Footnotes
    Support  the National Basic Research Program of China (Grant No. 2007CB512204)
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 2758. doi:
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      J. Wu, S. Zhang, X. Sun; Neuroprotective Effect of Up-regulated Sonic Hedgehog in Retinal Ganglion Cells Following Chronic Ocular Hypertension. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2758.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : To determine sonic hedgehog (Shh) expression and whether it exerts neuroprotective effects on RGCs in a rat chronic ocular hypertension model.

Methods: : Intraocular pressure (IOP) elevation was induced in rats by episcleral veins cautery. Protein and mRNA expressions of Shh were determined by immunohistochemistry, western blotting and real-time PCR. Exogenous Shh and its inhibitor cyclopamine were injected intravitreally to examine their effects on RGC survival after ocular hypertension by the counting of retrograde Dil-labeled RGCs. Shh signal pathway mediating neuroprotective effects were characterized using Western blotting and real-time PCR.

Results: : IOP elevated-retinas showed a 2.1- to 4.4-fold increase in Shh expression, compared to the control eyes (p<0.05). Exogenous Shh significantly promotes RGC survival 2 and 4 weeks after ocular hypertension, whereas cyclopamine increased RGC loss. 15.26% ± 1.57% RGCs were lost 2 weeks after IOP elevation in the PBS-treatment groups. In contrast, Shh-treated retinas lost only 4.54% ± 0.36% of RGCs (P<0.01). The injected cyclopamine reduced the number of RGCs by ~70% in a dose-dependent manner compared with the vehicle control after ocular hypertension. Western blotting and real-time PCR revealed that Smo, a shh signal transducer, and transcription factor Gli1 were significantly up-regulated in RGCs following chronic ocular hypertension or Shh-intravitreal treatment. Ptc, a shh binding receptor, However, was not detectably up-regulated both in mRNA and protein expression.

Conclusions: : Shh and its signal transducer Smo are up-regulated in a time-dependent manner in retinas exposed to ocular hypertension and that Shh, either endogenous or exogenous, has neuroprotective effects on damaged RGCs in a well-established rat model of chronic hypertension. Shh may exert neuroprotective effects by relieving the inhibition of Smo and subsequently activating transcriptional factor Gli1.

Keywords: ganglion cells • gene/expression • neuroprotection 

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