April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Expression of the TRPV Family in the DBA/2J Mouse Model of Glaucoma
Author Affiliations & Notes
  • K. W. Ho
    Vanderbilt Eye Institute, Vanderbilt University, Nashville, Tennessee
  • S. F. Juliao
    Vanderbilt Eye Institute, Vanderbilt University, Nashville, Tennessee
  • B. Zhao
    Vanderbilt Eye Institute, Vanderbilt University, Nashville, Tennessee
  • R. M. Sappington
    Vanderbilt Eye Institute, Vanderbilt University, Nashville, Tennessee
  • D. J. Calkins
    Vanderbilt Eye Institute, Vanderbilt University, Nashville, Tennessee
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2125. doi:
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      K. W. Ho, S. F. Juliao, B. Zhao, R. M. Sappington, D. J. Calkins; Expression of the TRPV Family in the DBA/2J Mouse Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2125.

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

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Abstract

Purpose: : Calcium-dependent cascades are important in the pathogenesis of glaucoma, whereby elevated intraocular pressure and injury at the optic nerve head induces an increase in Ca2+ in the retinal ganglion cells. Ca2+ conductance is amplified by activation of the transient receptor potential vanilloid (TRPV) family of cation-gating subunits that form either homo- or heteromeric functional channels with one another. We examined expression levels of TRPV1-6 in the retina of the DBA/2J mouse model of glaucoma to determine their significance in disease pathogenesis.

Methods: : Retinas were harvested from DBA/2J and DBA/2J-Gpnmb+/SjJ mice between 3 and 10 months of age. DBA/2J retinas were also grouped according to low or elevated ocular pressure. RNA was extracted and synthesized to cDNA, and quantitative RT-PCR was used to determine expression of TRPV1-6 with 18s RNA as the internal control.

Results: : The TRPV family, with the exception of TRPV5, was expressed in both DBA/2J-Gpnmb+/SjJ and DBA/2J retinas. TRPV3, 4 and 6 expression levels were down-regulated with both age and pressure in the DBA/2J retina, resulting in a nearly 90% (on average) decrease by 8-10 months (p<0.03, n=6). With elevated pressure TRPV2 levels decreased 60% at the two ages examined (3-5 and 8-10 months; p<0.0006, n=6). In contrast, TRPV1 expression increased with age (83%) and was significantly up-regulated in both young (157%) and old (529%) DBA/2J retinas with elevated pressure (p<0.0002, n=6).

Conclusions: : Increased expression of TRPV1 in the DBA/2J with elevated pressure supports the idea that the channel may be involved in glaucomatous progression. We have shown previously that antagonism of TRPV1 can reduce intracellular Ca2+ and apoptosis of retinal ganglion cells exposed to elevated pressure in vitro. Determining the source of the Ca2+ increase by TRPV1 activation and downstream effectors involved in TRPV1 signaling may elucidate the pathological relevance of TRPV1 up-regulation in glaucoma.

Keywords: ganglion cells • calcium • gene/expression 
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