Feedback Regulation of Intracellular Hydrostatic Pressure in Surface Cells of the Lens

Junyuan Gao, Xiurong Sun, Thomas W. White, Nicholas A. Delamere, Richard T. Mathias

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

In wild-type lenses from various species, an intracellular hydrostatic pressure gradient goes from ∼340 mmHg in central fiber cells to 0 mmHg in surface cells. This gradient drives a center-to-surface flow of intracellular fluid. In lenses in which gap-junction coupling is increased, the central pressure is lower, whereas if gap-junction coupling is reduced, the central pressure is higher but surface pressure is always zero. Recently, we found that surface cell pressure was elevated in PTEN null lenses. This suggested disruption of a feedback control system that normally maintained zero surface cell pressure. Our purpose in this study was to investigate and characterize this feedback control system. We measured intracellular hydrostatic pressures in mouse lenses using a microelectrode/manometer-based system. We found that all feedback went through transport by the Na/K ATPase, which adjusted surface cell osmolarity such that pressure was maintained at zero. We traced the regulation of Na/K ATPase activity back to either TRPV4, which sensed positive pressure and stimulated activity, or TRPV1, which sensed negative pressure and inhibited activity. The inhibitory effect of TRPV1 on Na/K pumps was shown to signal through activation of the PI3K/AKT axis. The stimulatory effect of TRPV4 was shown in previous studies to go through a different signal transduction path. Thus, there is a local two-legged feedback control system for pressure in lens surface cells. The surface pressure provides a pedestal on which the pressure gradient sits, so surface pressure determines the absolute value of pressure at each radial location. We speculate that the absolute value of intracellular pressure may set the radial gradient in the refractive index, which is essential for visual acuity.

Original languageEnglish (US)
Pages (from-to)1830-1839
Number of pages10
JournalBiophysical Journal
Volume109
Issue number9
DOIs
StatePublished - Nov 3 2015

ASJC Scopus subject areas

  • Biophysics

Fingerprint

Dive into the research topics of 'Feedback Regulation of Intracellular Hydrostatic Pressure in Surface Cells of the Lens'. Together they form a unique fingerprint.

Cite this