Conjunctival transdifferentiation induced by systemic vitamin A deficiency in vascularized rabbit corneas.

Abstract

Conjunctival transdifferentiation, the process in which conjunctival epithelium transforms into a cornea-like epithelium with the loss of goblet cells during the healing of a total corneal epithelial defect, can be retarded or reversed by corneal neovascularization. We have previously shown that this process normally occurring on non-vascularized corneas can be retarded or reversed by topical retinoids, suggesting that vitamin A may be one of the factors from blood circulation which is responsible for modulating transdifferentiation. Herein, we have examined the effect of systemic vitamin A deficiency on vascularized corneas starting 4 months after epithelial denudation, and compared this deficient group with their vascularized and non-vascularized controls. Mean serum retinol level (microgram/dl) (n = 4) measured by HPLC was gradually reduced from 83 of the controls to 20 in a 10 month follow-up. Topographical analysis disclosed a centrifugal loss of goblet cell density with time. Histology showed complete transdifferentiation in vascularized areas at 9 months, initiated by the loss of mucin contents from receding zones first noted at 2 months. Using impression cytology, all corneas were not keratinized and all conjunctivas maintained a normal goblet cell density at 10 months. These results indicate that conjunctival epithelium on corneal surface is more sensitive to the decrease of serum vitamin A levels than that on conjunctiva, and support the hypothesis that the relative vitamin A deficiency on vascularized corneas can also result in the conjunctival transdifferentiation.