Regression of Cataracts in the Offspring of Galactose Fed Rats

Abstract

3 days after conception, pregnant Sprague-Dawley rats were fed a diet of galactose + ground lab chow, glucose + ground lab chow, or ground lab chow alone. After delivery, mothers were fed lab chow alone. The offspring were sacrified at 0, 5, 10, 20 and 30 days after birth. Lenses were fixed and processed for light and electron microscopy. Gross observation showed that lenses from offspring of animals fed lab chow or lab chow + glucose were transparent at all times. In contrast, lenses from the offspring of galactose-fed mothers were totally opaque at birth. At 10 and 20 days postpartum the lenses from the offspring of galactose-fed animals displayed opaque regions which were interspersed with transparent areas. Opacities were no longer noted at 30 days postnatal. Thus, at the gross level, the cataracts formed during the period of fetal development appear to be completely reversible. At the ultrastructural level, the overall orientation of the epithelium and the overlying capsule was similar in all lenses examined. However, in the experimental group the fiber membranes were disrupted, and larger inter- and intracellular spaces were noted. The fibers were swollen and contained electron-dense aggregates of variable size. The extent of the galactose-induced damage assessed at the fine structural level regressed as the age of the offspring increased. Lenses and plasma from neonates and mothers were subjected to gas-liquid chromatography for determination of hexoses and polyols. Elevated levels of hexoses and polyols were found in the lenses and plasma of the newborn rats which had been exposed to galactose suggesting that the accumulation of polyols, which triggers cataract formation in older animals, also initiates cataract formation in the newborn.

Scanning Electron Microscopy of Lens

“…This report describes SEM observations made on lenses from offsprings of galactose-fed mothers. This study compliments our earlier report in which we described galactose-induced alterations and their reversal in newborn-rat lenses with TEM and biochemical techniques [ Unakar et al, 1979],…”

“…In this study cataractous changes in fetal lenses were induced through maternal feeding of galactose-containing diet during preg nancy [Unakar et al, 1979]. Earlier investigations of Batinon and Kaan [1939] and Bannon et al [1945] and Segal and Bernstein [1963] demon strated cataractogenic changes in fetal and newborn rat lenses of mothers fed galactose diet during gestation.…”

“…Earlier investigations of Batinon and Kaan [1939] and Bannon et al [1945] and Segal and Bernstein [1963] demon strated cataractogenic changes in fetal and newborn rat lenses of mothers fed galactose diet during gestation. The opacities thus induced in fetuses are completely reversible [Unakar et al, 1979] as opposed to partial reversal of such opacities in young-rat lenses [Fournier and Pattterson, 1970;Reddy et al, 1976;Unakar etal., 1978], The induction of galactose cataracts and subsequent reinstatement of tissue transparency provides a good model to study both cataractogenesis and reversal of opacities. In our laboratory we have initiated studies using TEM, scanning electron microscope (SEM) and some biochemical approaches to investigate these processes.…”

Activity of Hepatic Galactose-Metabolizing Enzymes in the Pregnant Rat and Fetus

“…We have observed that cataracts do not develop in pregnant rats fed a high galactose diet for the 21 days of gestation, whereas they are found in young male rats fed the same diet for the same number of days (2,3). Others have reported that pregnant rat lenses are clear until 48 h after parturition when cataractous changes precipitously appear (4). These data suggest that pregnancy affords protection of the female from galactose toxicity.…”

Reversal of Stage-I Sugar Cataract by Sorbinil, an Aldose Reductase Inhibitor

“…The time-depen dent reparative process involved: a decrease in lens dulcitol, gradual recovery of existing fiber thickness and interdigitation, produc tion of new cells [3]. In addition, diet-in duced cataract reversal was reported by Unakar et al [18] and Unakar and Tsui [19,20]. Using a 50% galactose diet, lenses were ex amined at different times until a mature cata ract was produced.…”