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