N-linked glycoside and glucuronide conjugates of the retinoid, acitretin, are biologically active in cornea and conjunctiva

The purpose of this study was to test two water-soluble, synthetic retinoid s, glucoseamido acitretin and glucuronamido acitretin, for biological activ ity in cells of the cornea and conjunctiva. Vitamin A-deficient, xerophthal mic rats were treated topically with these retinoids, and corneas were exam ined histologically for effects on epithelial keratinization. The effect of these retinoids on the proliferation of rabbit conjunctival fibroblasts in culture was also investigated. Glucoseamido acitretin treatment restored a normal cornea after eight to nine days of treatment, while no improvement was observed in the vehicle-treated corneas. Likewise, glucuronamido acitre tin application restored a normal corneal surface and reversed keratinizati on after eight to ten days of treatment. These retinoids caused no irritati on of the eye or ocular adnexa. In culture, exposure of conjunctival fibrob lasts to glucoseamide acitretin inhibited cell proliferation. Cultures expo sed to glucoseamido acitretin at 10(-8)M or 10(-6)M had cell densities 77.3 % and 51.9% of control, respectively, after seven days. Glucuronamido acitr etin also inhibited cell proliferation. Cultures exposed to glucuronamido a citretin at 10(-8)M had a cell density of 69.2% of control at day seven, wh ile at 10(-6)M this retinoid completely inhibited cell proliferation. These results show that glucoseamide acitretin and glucuronamido acitretin are b iologically active in the cornea and conjunctiva, and may be considered for ophthalmic use in diseases involving abnormalities of ocular surface cell differentiation or hyperproliferation of fibroblasts.