March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
The TRPV1 Response to Stress of Retinal Ganglion Cells
Author Affiliations & Notes
  • Nicholas J. Ward
    Ophthal & Vis Sciences, Vanderbilt Eye Institute, Nashville, Tennessee
  • Karen W. Ho
    Ophthal & Vis Sciences, Vanderbilt Eye Institute, Nashville, Tennessee
  • Tatiana N. Sidorova
    Ophthal & Vis Sciences, Vanderbilt Eye Institute, Nashville, Tennessee
  • David J. Calkins
    Ophthal & Vis Sciences, Vanderbilt Eye Institute, Nashville, Tennessee
  • Footnotes
    Commercial Relationships  Nicholas J. Ward, None; Karen W. Ho, None; Tatiana N. Sidorova, None; David J. Calkins, None
  • Footnotes
    Support  Melza and Theodore Barr and GRF (DJC), AHAF (DJC), NEI Grant (5R01EY017427-03) (DJC), RPB (DJC), NEI Core Grant (5P30EY008126-19) (DJC), NEI Training (5T32EY007135-17) (NJW), Dept Unrestricted (DJC)
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6593. doi:
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    • Get Citation

      Nicholas J. Ward, Karen W. Ho, Tatiana N. Sidorova, David J. Calkins; The TRPV1 Response to Stress of Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6593.

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

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Abstract

Purpose: : Within the CNS, transient receptor potential vanilloid 1 (TRPV1) expression and localization in neurons is affected by injurious stressors and pathology. This channel gates Ca2+ influx, and influences survival of retinal ganglion cells (RGCs) in response to pressure in vitro. In glaucoma, Ca2+-mediated cascades modulate RGC degeneration, thus TRPV1 may affect RGC survival in vivo as well. To characterize the TRPV1-mediated stress response in glaucomatous neurodegeneration, we examined TRPV1 expression and localization in the retina and optic nerve head (ONH) of DBA/2J mice as well as TRPV1 activation in RGCs in vitro.

Methods: : Whole-mount retinas from DBA/2J mice between the ages of 3 to 19 months were used for detection of TRPV1 mRNA by fluorescent in situ hybridization (FISH) and protein by immunohistochemistry (IHC). RGC-specific TRPV1 FISH signal was identified via colocalization with SMI-31 immunolabeling, and intensity quantified across age groups. Free-floating ONH sections were used for TRPV1 FISH and IHC. Primary RGC cultures were isolated from P1-3 rat retinas using anti-Thy1.1/CD90 immunomagnetic purification. Cultures were treated with TRPV1-specific agonist capsaicin for Fluo-4 intracellular Ca2+ imaging.

Results: : TRPV1 mRNA exhibited widespread retinal localization to SMI-31+ RGC somas, and intensity in RGCs increased 155±13% 3 to 8 months of age (p<0.05). TRPV1 mRNA decreased in RGCs with dysfunctional transport indicated by accumulated phosphorylated neurofilament (p<0.001). Conversely, TRPV1 protein increased in these dysfunctional RGCs, particularly in the cytosol. Diffuse TRPV1 protein localization within RGC somas at 5 months appeared to increase with age in DBA/2J retinas. Beginning at the 8 month time point TRPV1 localization appeared to redistribute from diffuse cytoplasmic to more membranous locations. At the ONH, TRPV1 mRNA did not appear to colocalize with SMI-31+ RGC axons, but rather localized to glia. TRPV1 protein exhibited robust astrocytic and limited axonal localization at the ONH. Treatment of RGC cultures with capsaicin indicated that TRPV1 activation increases translocation of TRPV1 to dendritic nodes (p<0.0001), where they focally gate Ca2+.

Conclusions: : Our results indicate an increase in RGC-specific TRPV1 with age and RGC dysfunction in DBA/2J mice. TRPV1 helps mediate pressure-sensitive influx of Ca2+ into RGCs, thus its expression and localization may modulate RGC survival in vivo. Our observation of dendritic translocation of TRPV1 upon activation in cultured RGCs may implicate this channel in a synaptic function during neuronal stress. Overall, such RGC-specific TRPV1 modulation may implicate the channel in pressure-sensitive degenerative processes.

Keywords: ganglion cells • ion channels • fluorescent in situ hybridization 
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