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Review
. 2016 Oct;32(8):504-508.
doi: 10.1089/jop.2016.0054. Epub 2016 Aug 11.

The Significance of TRPV4 Channels and Hemichannels in the Lens and Ciliary Epithelium

Nicholas A Delamere  1 , Amritlal Mandal  1 , Mohammad Shahidullah  1
Affiliations
Review

The Significance of TRPV4 Channels and Hemichannels in the Lens and Ciliary Epithelium

Nicholas A Delamere et al. J Ocul Pharmacol Ther. 2016 Oct.

Abstract

To function normally, all cells must maintain ion homeostasis, establish a membrane potential, and regulate water content. These actions require active Na-K transport provided by Na,K-ATPase. The lens, however, is made up almost entirely of fiber cells that have little or no Na,K-ATPase activity. Lens ion and water homeostasis rely on Na,K-ATPase activity in a small number of cells at the periphery of epithelium monolayer. Therefore, the function of the epithelium must be integrated with the needs of the fiber mass. This suggests that a remote control mechanism may adjust Na,K-ATPase activity to match increases or decreases of ion leakage, which may occur a considerable distance away. Here, we review evidence that TRPV4 channels in the epithelium become activated when the lens is subjected to osmotic- or damage-induced swelling. This triggers a chain of events in the lens epithelium that opens connexin hemichannels, allowing ATP release that stimulates purinergic receptors, activates Src family tyrosine kinases, and increases Na,K-ATPase activity. Recent studies also revealed functional connexin hemichannels along with TRPV4 channels in nonpigmented ciliary epithelial (NPE) cells that secrete aqueous humor into the eye. Because TRPV4 channels are mechanosensitive, we speculate they might enable the NPE to respond to stimuli such as mechanical distortion associated with volume homeostasis during fluid transfer across the ciliary epithelium or changes in intraocular pressure.

Keywords: Na,K-ATPase activity; TRPV4; ciliary epithelium; hemichannels; lens epithelium; remote sensing.

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Conflict of interest statement

Author Disclosure Statement No competing financial interests exist.

Figures

<b>FIG. 1.</b>
FIG. 1.
In a single cell (a), Na-K homeostasis is achieved automatically because Na,K-ATPase activity increases or decreases in response to fluctuations in cytoplasmic sodium concentration at the Na+ binding site on the cytoplasmic face. Na-K homeostasis is more complicated when the cell is coupled to one (b) or more cells that lack Na,K-ATPase (c). It must export Na+ ions that enter at a distant site. This is the case in the lens (d) where Na,K-ATPase is located in the epithelium but not fibers. (d) Is adapted from Mathias et al. It depicts how the arrangement of Na,K-ATPase, K channels, and gap junctions at the lens surface creates a circulating flow of current/ions through coupled cells of the fiber mass. In an intact lens, the flow exits at the equator and enters at the anterior and posterior poles.
<b>FIG. 2.</b>
FIG. 2.
Simplified model showing key elements of the swelling response in which activation of TRPV4 channels causes connexin hemichannels in the epithelium to open. This allows release of ATP that stimulates P2Y purinergic receptors. Then, SFKs are activated and Na,K-ATPase activity increases. The hemichannel opening—ATP release step, is a must. The response is abolished by hydrolysis of released ATP or blockade of either TRPV4 or hemichannels. SFKs, Src family tyrosine kinases.
<b>FIG. 3.</b>
FIG. 3.
Western blot showing TRPV1 expression in native (Nat) and cultured (Cult) porcine lens epithelium. Pig kidney (PK) was used as a positive control. MM, molecular marker.
<b>FIG. 4.</b>
FIG. 4.
The ciliary epithelial bilayer. The scheme on the left depicts the localization of transport mechanisms and is adapted from McLaughlin et al. The model is a simplification since transport activity is not uniform over the ciliary epithelial surface. Electron microprobe analysis of rabbit ciliary epithelium indicates enhanced secretion posteriorly and enhanced absorption anteriorly. Aqueous humor flow occurs in the PE-to-NPE direction. The PE and NPE are coupled by gap junctions and function in the manner of a syncytium. Na,K-ATPase activity and protein expression are highest at the basolateral, aqueous humor-facing surface of the NPE. In respect to coupling and Na,K-ATPase distribution, the tissue is similar to the 2-cell model shown in Fig. 1. NPE, nonpigmented ciliary epithelium; PE, pigmented ciliary epithelium.
<b>FIG. 5.</b>
FIG. 5.
Western blot (left panel) study shows the presence of TRPV4 in porcine NPE and immunolocalization (right panel) study shows its location on the basolateral membrane.
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References

    1. Bassnett S., Shi Y., and Vrensen G.F. Biological glass: structural determinants of eye lens transparency. Philos. Trans. R. Soc. Lond. B Biol. Sci. 366:1250–1264, 2011 - PMC - PubMed
    1. Tamiya S., Dean W.L., Paterson C.A., and Delamere N.A. Regional distribution of Na,K-ATPase activity in porcine lens epithelium. Invest. Ophthalmol. Vis. Sci. 44:4395–4399, 2003 - PubMed
    1. Delamere N.A., and Dean W.L. Distribution of lens sodium-potassium-adenosine triphosphatase. Invest. Ophthalmol. Vis. Sci. 34:2159–2163, 1993 - PubMed
    1. Gao J., Sun X., Yatsula V., Wymore R.S., and Mathias R.T. Isoform-specific function and distribution of Na/K pumps in the frog lens epithelium. J. Membr. Biol. 178:89–101, 2000 - PubMed
    1. Giaume C., Leybaert L, Naus CC, and Sáez JC. Connexin and pannexin hemichannels in brain glial cells: properties, pharmacology, and roles. Front. Pharmacol. 4:88, 2013 - PMC - PubMed

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