Henry N. Fukui

Philly mouse: A new model of hereditary cataract

Abstract Philly mouse is a new strain of mice derived from the Swiss-Webster strain which develops hereditary cataracts visible to the naked eye ca. 5–6 weeks after birth. Slit lamp examinations of the apparently clear lenses of 15 day mice indicate the presence of faint anterior opacities which progress, involving the suture area, by day 25. By 30 days a nuclear opacity develops which surrounds the nucleus by day 35. At the same time the anterior subcapsular opacity becomes diffuse and pronounced as the cataract becomes obvious to the naked eye. Biochemical studies indicate that an osmotic cataract is formed in the Philly mouse. By ca. 20 days of age there is an increase in lens water along with an alteration in electrolyte levels. Lenticular sodium rapidly increases while potassium levels decrease. Concomitant with cataract formation is an increase in total lenticular calcium and a decrease in lens dry weight, reduced GSH and ATP. In transport studies, no significant difference between the Philly and control lens was seen in the accumulation of AIB. When rubidium was substituted for potassium a decreased accumulation in the Philly lens older than 20 days was correlated with increased rubidium leak-out. This decreased accumulation due to increased leak-out appears to be the key biochemical change that accounts for osmotic cataract formation and it suggests the possibility of a defect in membrane permeability.

Swelling of the lens fibers.

Abstract Lens cells of congenital mouse cataract (Nakano and Fraser strains) and galactose-fed rats were studied by scanning electron microscopy. Similarly lens cells of normal young mice and rats were examined as controls. Normal lenses of young rodents consist of lens fibers in all maturation stages which have been demonstrated in humans and in monkeys. Lens cells in the congenitally cataractous lenses are irregular in size and shape in the earlier stage of the cataract formation. Swelling of the lens cell occurs corresponding to the occurrence of early optical opacity. Swelling of the cell occurs segmentally in congential cataractous lenses; in the apical ends (Fraser) and in the posterior ends (Nakano). Similar swelling of the lens cell is observed in the main cell body in the superficial lens cortex of galactose-fed rats. However, numerous intercellular cysts are formed by the accumulation of fluid which may have been pumped out of the cells before the cells became degenerative. These numerous shrunken fibers are present among swollen cells in both congenital and galactose-induced cataractous lenses.

A possible cataractogenic factor in the Nakano mouse lens

Abstract A factor present in the Nakano mouse lens is an inhibitor of NaK ATPase. This inhibitor is not found in the normal mouse lens. It is not associated with any of the major crystallins but is found with the low molecular weight components. It is resistant to high temperatures and to acid and alkaline pHs. It appears to be a polypeptide since its activity is abolished by treatment with carboxy-peptidase A and leucine amino peptidase. Other properties of the inhibitor indicate that this factor appears quite different from other substances which inhibit NaK ATPase.

The effect of hydrogen peroxide on the rubidium transport of the rat lens

Abstract The possibilities of ascorbic acid and hydrogen peroxide, a product of ascorbate oxidation, influencing the cation transport mechanism in the lens have been further explored. Since the possibility that the ascorbate effect on the cation transport of the lens may be largely due to the hydrogen peroxide further studies were made with peroxide. When the lens was incubated in a medium containing hydrogen peroxide but not glucose, the uptake of rubidium ion was adversely affected. Thus peroxide had similar effects as ascorbate. The addition of glucose to the medium abolishes both the hydrogen peroxide or the ascorbate effect. Hydrogen peroxide, lowered the glutathione level of the lens whereas ascorbate did not.

Cataract Prevention in Diabetic Octodon Degus with Pfizer's Sorbinil

The Octodon degus has been reported to have higher aldose reductase activity in the lens compared to the gerbil and rat. When made diabetic the degus develop cataracts within 4 weeks. We have been able to completely prevent cataract formation in diabetic degus using Pfizers sorbinil for up to 6 months. This is further evidence of the role of aldose reductase in the formation of cataracts in diabetes.

Intraocular Irrigating Solutions and Lens Clarity

By in vitro incubation of rhesus monkey lenses at 37degreesC, we determined that solutions superior to intraocular irrigating solutions in common clinical use could be prepared by aspetically adding commerically available solutions of dextrose 5% in water and sodium bicarbonate to either Ringers injection or Ringers lactate solutions. While not as effective as glutathione-bicarbonate-Ringers solution (G-B-R) in maintaining lens clarity, these mixtures can be prepared easily in the operating room (in contrast to G-B-r) and may improve surgical results in procedures requiring prolonged intraocular irrigation.

Studies on primary cultures of adult lens cells from normal and hereditary cataractous mice.

Abstract Lens epithelial cells from normal and congenital cataractous mice strains were cultured under similar conditions. Both normal and cataractous cells actively propagated and reached confluency on the eleventh day. These cells, thereafter, underwent morphological changes characterized by cell elongation, aggregation and formation of lentoid bodies at about 15 days. Electron microscopy revealed these lentoid bodies to consist of immature lens cells. These structures derived from cataractous cells had numerous vacuoles in the cytoplasm much more so than in the normal lens cells. In addition, some lentoid bodies closely resembled mature fibers of the intact lens. It was also demonstrated that these lentoid bodies showed positive immunofluorescence when reacted with fluorescent antiserum to γ-crystallin. There were certain differences observed between the cultured cells derived from normal lens and Nakano cataract. The disappearance of organelles and denucleation process were delayed in the lentoid bodies found in cultured Nakano cells when compared to normal cell culture. In addition a second type of lentoid body, although present as a minor population, was observed in the Nakano cell culture. Other subtle differences were observed during the course of culturing normal and cataractous lens cells.

Properties of a Na-K ATPase inhibitor in cultured lens epithelial cells

Abstract A Na-K ATPase inhibitor has been isolated from cultured lens epithelial cells from the Nakano mouse. This inhibitory activity elutes from a CM-Sephadex column in the same fraction as the inhibitor from intact Nakano lens. The inhibitor is a polypeptide sensitive to leucine aminopeptidase as well as car☐ypeptidase A. In addition, the inhibitor isolated from the cultured lens cells has the same molecular weight as the one present in the Nakano lens. Thus, the inhibitory activity from the cultured cells appears to be similar to that obtained from whole lens.