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D. Krizaj, P. Witkovsky, P. Barabas, C. Punzo, R. C. Renteria, W. Liedtke, W. H. Huang; Expression and Function of TRPV4 Channels in the Vertebrate Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1860.
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© ARVO (1962-2015); The Authors (2016-present)
TRPV4 ion channels integrate extracellular signals (osmotic pressure, stretch, temperature), plasma membrane calcium fluxes with the activity of intracellular signaling pathways. TRPV4 channels are ubiquitous across the CNS where they function as osmotic (hypotonicity) and mechanosensors. We examined expression and localization of TRPV4 mRNA and protein in the mouse retina and investigated their contribution to calcium signaling and spontaneous activity in retinal ganglion neurons.
Retinas from wild type mice, DBA/2J and transgenic mice expressing GFP under the TRPV4 promoter were investigated with in situ hybridization, RT-PCR, immunohistochemistry, calcium imaging and multielectrode arrays (MEAs). Imaging was performed in isolated cells and slices from tiger salamander and mouse retinas. MEAs were utilized in the retinal wholemount preparation.
TRPV4 mRNA was localized to the outer and inner nuclear layers and to prominently labeled RGCs. The signal in transgenic mice expressing GFP driven by the TRPV4 promotor was confined to RGC perikaryal cytoplasm. Exposure to the TRPV4 agonist 4-alpha PDD (10 uM) transiently elevated intracellular calcium concentration in subsets of putative salamander and mouse RGCs. 4 -alpha PDD-evoked increases were antagonized by 20 uM Ruthenium Red. The agonist also induced a transient increase in firing in a subset of RGCs recorded with MEAs. TRPV4 mRNA content was significantly increased in the DBA/2J mouse glaucoma model relative to age-matched control retinas.
These results suggest that TRPV4 is localized to retinal ganglion neurons. The upregulation of TRPV4 gene expression in DBA/2J retinas potentially implicates this calcium-permeable osmosensitive channel in cellular remodeling observed in glaucoma.
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