title: Lens intracellular hydrostatic pressure is generated by the circulation of sodium and modulated by gap junction coupling.
abstract: We recently modeled fluid flow through gap junction channels coupling the pigmented and nonpigmented layers of the ciliary body. The model suggested the channels could transport the secretion of aqueous humor, but flow would be driven by hydrostatic pressure rather than osmosis. The pressure required to drive fluid through a single layer of gap junctions might be just a few mmHg and difficult to measure. In the lens, however, there is a circulation of Na(+) that may be coupled to intracellular fluid flow. Based on this hypothesis, the fluid would cross hundreds of layers of gap junctions, and this might require a large hydrostatic gradient. Therefore, we measured hydrostatic pressure as a function of distance from the center of the lens using an intracellular microelectrode-based pressure-sensing system. In wild-type mouse lenses, intracellular pressure varied from ∼330 mmHg at the center to zero at the surface. We have several knockout/knock-in mouse models with differing levels of expression of gap junction channels coupling lens fiber cells. Intracellular hydrostatic pressure in lenses from these mouse models varied inversely with the number of channels. When the lens' circulation of Na(+) was either blocked or reduced, intracellular hydrostatic pressure in central fiber cells was either eliminated or reduced proportionally. These data are consistent with our hypotheses: fluid circulates through the lens; the intracellular leg of fluid circulation is through gap junction channels and is driven by hydrostatic pressure; and the fluid flow is generated by membrane transport of sodium.
authors.affiliation: Department of Physiology and Biophysics, SUNY at Stony Brook, NY 11794, USA.
authors.forename: Junyuan
authors.initials: J
authors.lastname: Gao
authors.forename: Xiurong
authors.initials: X
authors.lastname: Sun
authors.forename: Leon C
authors.initials: LC
authors.lastname: Moore
authors.forename: Thomas W
authors.initials: TW
authors.lastname: White
authors.forename: Peter R
authors.initials: PR
authors.lastname: Brink
authors.forename: Richard T
authors.initials: RT
authors.lastname: Mathias
mesh_terms: D000818:Animals; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D017629:Gap Junctions / Q000502:physiology*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006874:Hydrostatic Pressure; D007908:Lens, Crystalline / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D012964:Sodium / Q000378:metabolism*; D000099264:Connexin 50
chemical_list: D017630:Connexins; D005136:Eye Proteins; D005979:Glutathione Peroxidase; D012964:Sodium; D000099264:Connexin 50; C082917:GJA3 protein, human