Topical all/trans retinoic acid rapidly corrects the follicular abnormalities of the rhino mouse. An ultrastructural study.

Abstract

Topical all-trans retinoic acid (RA) has been shown to transform the horn-filled utriculi of the rhino mouse into normal follicles. We studied the early events by light and electron microscopy. Reduction in diameters of the utriculi was quantified by image analysis of whole mounts. Topical RA at 0.05% in ethanol/propylene glycol was applied daily and biopsies were taken after 1, 2, 3 and 6 days of treatment. By electron microscopy, after 3 days of RA treatment there was a great increase in the size and density of laminated membrane coating granules (MCGs) which had fused to the apical membranes of the upper granular cells. Thereafter, corneocytes within the lumina of the utriculi showed fewer desmosomes and a loss of intercellular material, accompanied by detachment from each other. Conversion to normal follicles was complete by 6 days. In whole mounts examined after 3 days of RA, there was a 75% reduction in the mean diameter of the utriculi. These results suggest that extrusion of the contents of enlarged MCGs into the intercellular corneocyte spaces facilitated separation of corneocytes, leading to rapid shedding, perhaps through the action of desmosome-lysing proteases. The conversion to normal follicles is consistent with the established role of retinoids in correcting abnormal differentiation.