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Grant

TRPV4 as a Remote Controller of Lens Function

Sponsored by National Eye Institute

$1.8M Funding
2 People
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Abstract

To function normally all cells must maintain ion homeostasis and regulate water content.These actions require active Na-K transport provided by NaK-ATPase. The lenshowever is a syncytium-like structure made up almost entirely of fiber cells that havelittle or no NaK-ATPase activity. Lens ion and water homeostasis relies on NaK-ATPaseactivity in a small number of cells at the periphery of epithelium monolayer. Thereforethe function of the epithelium must be integrated with the needs of the fiber mass. Weenvision there to be a remote control mechanism that adjusts NaK-ATPase activity tomatch increases or decreases of ion leakage that may occur a considerable distanceaway. The mechanism depends on TRPV4 an ion channel. We propose studies todetermine the detailed workings of this remote control mechanism and its functionalimpact on the lens. Aim 1 includes studies to determine how the lens uses TRPV4 tosense a change in the fiber mass and activate Src Family Tyrosine Kinases (SFKs) in theepithelium. Studies proposed in Aim 2 will determine how lens epithelial cells use SFKsto change NaK-ATPase activity. Aim 3 describes the use of magnetic resonanceimaging (MRI) and atomic absorption spectroscopy to measure the impact of the TRPV4remote control mechanism on lens water and ion homeostasis. The significance tohuman well-being is that cataract is frequently associated with failed homeostasis.

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