Previous studies of topical
retinoic acid for treatment of ocular surface disease met with limited success due to instability and irritancy of the
retinoid and lack of efficacy in
keratoconjunctivitis sicca. There has, however, been continued interest in the treatment of
mucin deficiency and cicatrizing
conjunctival diseases, such as
ocular cicatricial pemphigoid (OCP), topically with
retinoids. In this study the
biological activity of stable, water-soluble, synthetic
retinoid, N-(4-hydroxyphenyl)
retinamide-O-
glucuronide (4-HPROG) was investigated in vivo and in vitro using conjunctival and corneal epithelium and fibroblasts.
Vitamin A-deficient rabbits with stage 3-4 corneal xerosis and squamous
metaplasia confirmed by conjunctival impression cytology were treated with topical 0.1%
4-HPROG in an
artificial tear vehicle for 3 weeks. Impression cytology was repeated at 2 and 3 weeks and at 3 weeks conjunctival biopsies were fixed for histology. Growth curves were generated using conjunctival fibroblasts of rabbits and humans (normals and patients with cicatrizing
conjunctival disease including OCP and
Stevens-Johnson syndrome) cultured in the 10(-8)-10(-6) M
4-HPROG. In vivo, corneal xerosis cleared in three days. A normal conjunctival epithelium was restored by 2 weeks and goblet cells were present by 3 wk, with no change in vehicle-treated controls. No ocular irritation occurred. In vitro, 10(-6) M
4-HPROG inhibits growth of rabbit conjunctival fibroblasts. The
retinoid had no effect on proliferation of conjunctival fibroblasts from normal humans but the doubling time of cells from patients with OCP increased significantly, from 50.9 +/- 10.01 h (control) to 61.5 +/- 8.95 h (
retinoid). Proliferation of conjunctival fibroblasts from a patient with
Stevens-Johnson syndrome was also inhibited. N-(4-hydroxyphenyl)
retinamide-O-
glucuronide is biologically active and merits further study to determine its efficacy in controlling conjunctival
fibrosis and treating ocular surface squamous
metaplasia.