title: Feedback Regulation of Intracellular Hydrostatic Pressure in Surface Cells of the Lens.
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.
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York.
authors.forename: Junyuan
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York.
authors.forename: Xiurong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: White
authors.affiliation: Department of Physiology and Biophysics, University of Arizona, Tucson, Arizona.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Delamere
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York. Electronic address: richard.mathias@sunysb.edu.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Mathias
mesh_terms: D000818:Animals; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D006874:Hydrostatic Pressure; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D046509:Tissue Culture Techniques; D014065:Tonometry, Ocular
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000254:Sodium-Potassium-Exchanging ATPase; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C486576:Trpv4 protein, mouse