May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Identification of Wnt Signaling Activity in Retinal Ganglion Cells in the Normal and Glaucomatous Mouse Retina
Author Affiliations & Notes
  • R. E. I. Nakamura
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
  • Y. Wang
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
  • M. L. Bajenaru
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
  • R. K. Lee
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
  • A. S. Hackam
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
  • Footnotes
    Commercial Relationships  R.E.I. Nakamura, None; Y. Wang, None; M.L. Bajenaru, None; R.K. Lee, None; A.S. Hackam, None.
  • Footnotes
    Support  Karl Kirchgessner Foundation Lois Pope Life Fellowship NEI core grant P30 EY014801 RPB Unrestricted grant (BPEI) 1R01EY017837-01A1 K08 EY016775
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5192. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      R. E. I. Nakamura, Y. Wang, M. L. Bajenaru, R. K. Lee, A. S. Hackam; Identification of Wnt Signaling Activity in Retinal Ganglion Cells in the Normal and Glaucomatous Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5192. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : An important therapeutic strategy for treating glaucoma and other optic neuropathies is to prevent retinal ganglion cell (RGC) death while maintaining neuronal function. Discovering signaling pathways that confer RGC survival will identify novel treatments for halting glaucoma progression and visual field loss. The Wnt pathway is an essential signaling cascade that is well characterized in development and oncology. We recently demonstrated that Wnt signaling rescued photoreceptors in retinal co-cultures exposed to oxidative stress (Yi, IOVS; 2007). In this study, we investigated Wnt signaling activity in RGCs in normal and high IOP mice.

Methods: : Wnt activity and Wnt gene expression was localized in the Wnt signaling reporter mouse line Tcf-LacZ and the rat RGC cell line RGC-5 using immunohistochemistry. Wnt signaling was measured using luciferase reporter assays and beta-catenin nuclear localization in RGC-5 cells. Microarray analyses were performed on DBA/2J and C57Bl/6 mice using Affymetrix arrays.

Results: : Wnt pathway activation was identified in RGC and INL layers in normal mouse retina. We also localized Wnt ligands (Dkk3) and receptors (Fzd3, Krm1/2, and LRP6) to RGCs. Wnt signaling was stimulated in RGC-5 cells by incubation with the Wnt activators Wnt3a and LiCl. To explore the role Wnt signaling plays in RGC survival in glaucoma, we analyzed gene expression in 12 month old DBA/2J mice. We found increased expression of Wnt pathway activators and decreased Wnt inhibitors, compared with age-matched controls, suggesting that the Wnt pathway is activated during RGC death.

Conclusions: : These data identify candidate Wnt activator proteins that are expressed during RGC death and demonstrate that RGCs are Wnt responsive cells. This suggests Wnt signaling is upregulated in RGCs in glaucomatous retinas. Because Wnt signaling is neuroprotective elsewhere in the retina and the CNS, we hypothesize that Wnt signaling protects RGCs in glaucoma.

Keywords: growth factors/growth factor receptors • signal transduction • ganglion cells 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×