RETINOID EFFECTS ON EPIDERMAL STRUCTURE, DIFFERENTIATION, AND PERMEABILITY

Abstract

Retinoids profoundly influence epidermal differentiation but the nature of their antikeratinizing activity and their mechanism of action is not known. Morphologic and histochemical findings were correlated with an assessment of stratum cohesion and water barrier integrity in adult hairless mice treated with 13-cis-retinoic acid [RO 4-3780, Accutane] or the aromatic retinoid, RO 10-9359 [ethyl-all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate, Tigason]. The synthetic retinoids produced dose-dependent alterations in transepidermal water loss, which were .apprx. 5-10 times greater in RO 10-9359-treated animals. In contrast to essential fatty acid deficiency, where diminished intercellular lamellar lipids may account for defective barrier function, these lipid-rich structures were intact in retinoid-treated tissues. Retinoids produced both epidermal and stratum corneum loosening, manifested both by the ready production of intraepidermal friction blisters and by ease of removal of cornified cells by tape stripping. Dyshesion correlated with loss of desmosomes and intra- and intercellular accumulation of amorphous material in the upper epidermis. Since these deposits lacked the tinctorial properties of mucin, dyshesion could not be ascribed to the development of mucous metaplasia. Dyshesion could not be attributed to gain or loss of membrane sugars demonstrated with rhodamine-conjugated lectins, as these changed only late in the course of retinoid treatment. The antikeratinizing basis for retinoid activity comprises dose-dependent alterations in transepidermal water loss and epidermal and stratum corneum loosening, which may, in turn, lead to loss of epidermal cohesion and abnormal barrier function. Mucous metaplasia and stratum corneum thinning do not have a major role.