Studies on the crystalline lens. XXII. Characterization of chloride movement based on the pump-leak model.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
K R Hightower
Publications and source records attributed to K R Hightower.
A review of the evidence that ultraviolet irradiation is a risk factor in cataractogenesis.
There are two approaches to the question of whether solar radiation contributes to human cataract. The first, epidemiological studies, investigates correlations between man's environmental UV dose and cataract frequency. The second, animal models, investigates the effects of varying UV strengths and spectra on lens opacification in vivo or in vitro. While the latter approach typically provides for direct evidence, the data must still be extrapolated to human lenses. Results of physiological studies suggest that UV photons interact with proteins of the epithelial cell membranes, in particular tryptophan residues, transport ATPases and cytoskeletal proteins. One hypothesis is that damage to ion pumps and channels accumulates over the years as repair processes incompletely restore membrane function. Peroxidative damage is likely in view of the formation of UV-induced lipid peroxides in the lens epithelial membranes. Loss of homeostatic control of ions, particularly Ca++, leads to crystallin disorder in small regions of the underlying fiber cells. In our diabetic cataract studies, intracellular Ca++ electrodes detected large shifts in intracellular Ca++ before bulk-lens changes were apparent. Similar occurrences likely characterize UV cataract. Our lab is one of few studying lens physiology and how it is altered following transient exposures to UV-B and UV-A, both of which pass through the cornea. Some changes include: loss of epithelial cell GSH; elevated Ca++; loss of membrane voltage; impaired transport of Na+; increased permeability to ions and water; inhibition of critical enzymes; and a decrease in the rate of membrane synthesis.
Animals↗
Cytotoxic effects of calcium on sodium-potassium transport in the mammalian lens.
Experiments were designed to investigate the effects of lens calcium on the Na/K pump since elevated calcium and sodium often accompanies lens opacification. An increase in lens calcium was accomplished by culturing lenses in calcium-rich media at 21 degrees C in the absence of poisons which might directly alter sodium transport. Calcium loaded lenses were subsequently incubated at 37 degrees C in a normal culture medium to assess membrane transport function. A five-fold increase in total lens calcium to 1.45mM, resulting in a 4% increase in membrane bound calcium, had little effect on the cation pump. However, an increase in lens calcium by a factor of 100 caused a 4-fold increase in membrane bound calcium, a 50% decrease in (Na/K)-ATPase activity, and a 40% decrease in 86Rb uptake after an incubation period of 20 hrs. Details of the mechanism of enzyme inhibition remain obscure, but the data suggest the inhibition is predominantly irreversible and does not involve an interaction between calcium and ATP.
Animals↗