Topical Treatment of Galactose Cataracts

Abstract

In experimental galactosemia, topical administration of aldose reductase inhibitor, l,3-dioxo-lH-benz-[de]-isoquinoline-(3H)-acetic acid (Alrestatin) was observed to decrease the level of dulcitol accumulated in the lens as compared to that in the control lens of the contralateral eye receiving the placebo only. In addition, topical application of Alrestatin led to a significant delay in the appearance of nuclear cataracts in eyes of galactosemic rats. The results are thus in conformity with the concept that aldose reductase plays a key role in initiating the formation of galactose cataracts and suggest the possibility of the usefulness of aldose reductase inhibitors in therapeutic ocular treatment of sugar cataracts. The formation of cataracts in galactosemia is initiated by accumulation of excessive dulcitol (galactitol) in the lens (Kinoshita, Merola, Satoh & Dikmak, 1962). Dulcitol, which is a hexahydric sugar alcohol, is formed in the lens by the reduction of galactose catalyzed by the enzyme aldose reductase (Van Heyningen, 1959). Previous studies have demonstrated that the cataractous changes can be attenuated, both in vitro (Kanoshita, Dvornik, Kraml & Gabbay, 1968) and in vivo (Dvornik, Duquesne, Krami, Sestanj, Gabbay, Kinoshita, Varma & Merola, 1973) by the use of compounds which inhibit aldose reductase. The obvious next step in the treatment of this form of cataract is to develop means of administering aldose reductase inhibitor directly in the eye in the form of aqueous drops or ointment. These studies may not only be of practical importance but can also serve to substantiate the findings of the earlier feeding experiments which required that control animals form a separate group. In the present studies, the experimental design was considered to be more ideal with one eye serving as a control while the contralateral eye is treated with aldose reductase inhibitor in the same galactosemic rat.