The significance, if any, of the increased sodium concentration in dKO mice is not known. Lens sodium concentration increases have been reported previously in hereditary cataract mice
41 42 and in human senile cataract.
43 As the Na
+ moves inward from surface of the lens, it is continuously crossing into fiber cells, driven by its transmembrane electrochemical gradient.
9 Once in the intracellular compartment, it reverses direction and flows from cell-to-cell via gap junctions toward the lens surface. The differentiating fibers have their gap junction coupling conductance concentrated in the equatorial region, so the intracellular current is directed to the equatorial surface epithelial cells. Recent studies
44 45 have shown that Na/K-ATPase activity is highly concentrated at the equatorial surface, where it can transport the intracellular flux of Na
+ out of the lens. Epithelial cells are responsible for essentially all the active transmembrane transport in the lens, including those involving Na/K-ATPase.
46 The activity of Na/K ATPase decreases with increasing age in humans, and this decrease occurs primarily in the inner nuclear region.
47 In experimental and hereditary cataracts in animals, loss in the activity of Na/K-ATPase has been associated with lens opacification.
47 Furthermore, Na/K-ATPase activity decreases in human cataracts. In severe cataractous human lenses, a marked decrease in the Na/K-ATPase activity has been demonstrated in all parts of the lens, in contrast to less severe cataracts, where the decrease in the enzyme activity occurs primarily in the cortical and nuclear regions.
47 Most of the Na/K-ATPase activities occur in epithelial cells of lenses.
46 It is interesting that the opacity of dKO lenses increased between 8 and 11 weeks of age, the same time as the increase in sodium level was observed. It is possible that there is a significant decrease of Na/K-ATPase activity in 11 week dKO mice and that it leads to more severe cataract compared with the moderate cataract in 8-week-old dKO mice. Duncan et al.
48 have studied the physiological status of human lens membranes of different ages in the population. They found that in human lenses, membrane potentials increased with age. All the older lenses had markedly higher calcium and sodium concentration that increased with age and grade of the cataract. Recently, it has been reported that human lens phospholipid changes with age and cataract.
49 As a result of the elevation of sphingolipid levels with species, age, and cataract, lipid hydrocarbon chain order, or stiffness, increases. Possibly the increased sphingolipid levels reduces calcium pump activity, among its many other effects.