The wnt signaling pathway protects retinal ganglion cell 5 (RGC-5) cells from elevated pressure

Miryam A. Fragoso, Hyun Yi, Rei E I Nakamura, Abigail S Hackam

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The Wnt pathway is an essential signaling cascade that regulates survival and differentiation in the retina. We recently demonstrated that retinal ganglion cells (RGCs) have constitutively active Wnt signaling in vivo. However, the role of Wnt in RGC viability or function is unknown. In this study, we investigated whether Wnt protects the retinal ganglion cell line RGC-5 from elevated pressure, oxidative stress, and hypoxia injuries. Expression of RGC marker genes in the RGC-5 cultures was confirmed by immunocytochemistry and PCR. We demonstrated that the Wnt3a ligand significantly reduced pressure-induced caspase activity in RGC-5 cells (n = 5, P = 0.03) and decreased the number of TUNEL-positive cells (n = 5, P = 0.0014). Notably, Wnt3a-dependent protection was reversed by the Wnt signaling inhibitor Dkk1. In contrast, Wnt3a did not protect RGC-5 cells from oxidative stress or hypoxia. Furthermore, Wnt3a significantly increased growth factor expression in the presence of elevated pressure but not in the presence of oxidative stress and hypoxia. These results indicate that Wnt3a induces injury-specific survival pathways in RGC-5 cells, potentially by upregulating neuroprotective growth factors. Therefore, activation of the Wnt pathway by Wnt3a could be investigated further as a tool to develop novel molecular therapeutic strategies for the prevention of RGC death in retinal disease.

Original languageEnglish
Pages (from-to)163-173
Number of pages11
JournalCellular and Molecular Neurobiology
Volume31
Issue number1
DOIs
StatePublished - Jan 1 2011

Fingerprint

Wnt Signaling Pathway
Retinal Ganglion Cells
Pressure
Oxidative Stress
Intercellular Signaling Peptides and Proteins
Retinal Diseases
In Situ Nick-End Labeling
Wounds and Injuries
Caspases
Retina
Cell Survival
Cell Death
Cell Culture Techniques
Immunohistochemistry
Ligands
Cell Line
Polymerase Chain Reaction

Keywords

  • Apoptosis
  • Brain-derived neurotrophic factor
  • Elevated hydrostatic pressure
  • Glaucoma
  • Nerve growth factor
  • Neuroprotection
  • Neurotrophin 3
  • RGC-5
  • Wnt pathway
  • Wnt3a

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

The wnt signaling pathway protects retinal ganglion cell 5 (RGC-5) cells from elevated pressure. / Fragoso, Miryam A.; Yi, Hyun; Nakamura, Rei E I; Hackam, Abigail S.

In: Cellular and Molecular Neurobiology, Vol. 31, No. 1, 01.01.2011, p. 163-173.

Research output: Contribution to journalArticle

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