The effects of age on lens transport.
OBJECTIVE
Age-related nuclear cataracts involve denaturation and aggregation of intracellular proteins. We have documented age-dependent changes in membrane transport in the mouse lens to see what might initiate changes in the intracellular milieu.


METHODS
Microelectrode-based intracellular impedance studies of intact lenses were used to determine gap junction coupling conductance, fiber and surface cell membrane conductances, effective extracellular resistivity, and intracellular voltage. Fiber cell connexin expression was detected by Western blotting. Intracellular hydrostatic pressure was measured with a microelectrode/manometer system. Concentrations of intracellular sodium and calcium were measured by intracellular injection of sodium-binding benzofuran isophthalate and Fura2, respectively.


RESULTS
In adult lenses, as age increased: fiber cell gap junction coupling conductance declined significantly, correlating with decreases in Cx46 and Cx50 labeling in Western blots; fiber and surface cell membrane conductances did not change systematically; effective extracellular resistivity increased monotonically; center to surface gradients for intracellular pressure, sodium, calcium, and voltage all increased, but in an interdependent manner that moderated changes. In newborn pup lenses, there were changes that did not simply fit with the above paradigm.


CONCLUSIONS
In newborn pup lenses, the observed changes may relate to growth factors that are not related to age-dependent changes seen in adult lenses. The major change in adult lenses was an age-dependent decrease in gap junction coupling, probably due to oxidative damage leading to degradation of connexin proteins. These changes clearly lead to compromise of intracellular homeostasis and may be a causal factor in age-related nuclear cataracts.
Department of Physiology & Biophysics, SUNY at Stony Brook, Stony Brook, New York.
Junyuan
J
Gao
Huan
H
Wang
Xiurong
X
Sun
Kulandaiappan
K
Varadaraj
Leping
L
Li
Thomas W
TW
White
Richard T
RT
Mathias
D000375:Aging / Q000523:psychology*; D000818:Animals; D001693:Biological Transport, Active; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D017630:Connexins / Q000378:metabolism; D017097:Electric Impedance; D017629:Gap Junctions / Q000502:physiology; D006874:Hydrostatic Pressure; D007908:Lens, Crystalline / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D012964:Sodium / Q000378:metabolism
D017630:Connexins; D012964:Sodium; D002118:Calcium
gap junction coupling conductance; intracellular calcium concentration; intracellular hydrostatic pressure; intracellular sodium concentration; lens size; membrane conductance; membrane water permeability; resting voltage