June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
TRPV4 channels enable the lens epithelium to respond to remote damage in the fiber mass.
Author Affiliations & Notes
  • Nicholas A Delamere
    Physiology, University of Arizona, Tucson, AZ
  • Mohammad Shahidullah
    Physiology, University of Arizona, Tucson, AZ
  • Footnotes
    Commercial Relationships Nicholas Delamere, None; Mohammad Shahidullah, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3561. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Nicholas A Delamere, Mohammad Shahidullah; TRPV4 channels enable the lens epithelium to respond to remote damage in the fiber mass.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3561.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: Na,K-ATPase activity is low or absent in lens fiber cells and Na,K-ATPase activity in the epithelium plays a critical role in ion and water homeostasis of the entire lens structure. We know from previous studies that Na,K-ATPase activity in the epithelium is subject to regulation by a TRPV4- and Src family tyrosine kinase-dependent mechanism. Here we tested whether the epithelium is able to increase Na,K-ATPase activity in response to a remote stimulus in the fiber mass.

Methods: The posterior pole of the intact pig lens was subjected to localized damage by a 2.5 mm diameter freeze-thaw wound (FT) then the lens was incubated for 2-30 min at 37 oC. At the end of the incubation period the lens epithelium was removed, homogenized and the rate of ouabain-sensitive ATP hydrolysis (Na,K-ATPase activity) measured or TRPV4 protein expression and Src family tyrosine kinase (SFK) activation in the epithelium were examined by a western blot approach. Data were analyzed by a t-test.<br />

Results: Localized freeze-thaw (FT) damage to lens fibers at posterior pole was found to cause SFK activation in the epithelium judged by an increase of pY416 SFK band intensity (treated:control = 4.3±0.8, p=0.001, n=3). The FT maneuver caused Na,K-ATPase activity to almost double (60.0±5.6 vs 33.1±6.3 nmoles ATP hydrolyzed/mg protein/30 min, p=0.001, n=5). The changes occurred within minutes. The lens expresses a mechanosensitive ion channel, TRPV4, and here we examined its distribution. TRPV4 protein was detected in the lens epithelium but not in the fiber cells. A TRPV4 channel antagonist, HC067947 (10 µM) suppressed the SFK phosphorylation response in lenses subjected to the FT maneuver (treated:control = 1.4±0.8, n=3). The FT-induced increase of Na,K-ATPase activity in the epithelium was suppressed in lenses exposed to either HC067947 or the SFK inhibitor PP2 (10 µM).

Conclusions: The findings point to a TRPV4-dependent mechanism that impacts Na,K-ATPase activity in the lens epithelium. The mechanism enables lens epithelial cells to sense remote damage in the fiber mass and respond by activating SFK and increasing Na,K-ATPase activity.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×