SEQUENCE OF MORPHOLOGICAL EVENTS DURING TOPICAL APPLICATION OF RETINOIC ACID ON THE RHINO MOUSE SKIN

In a study of the comedolytic action of retinoids on the epidermal pseudocomedones of rhino mouse skin, the earliest changes and the sequence of events induced by the treatment were investigated. Rhino mice were treated topically with all-trans retinoic acid and at various time intervals from day 0 to 3 weeks, histological and ultrastructural studies as well as quantification of mast cells were performed. The earliest changes occurred in the dermis after 2 days of treatment and were characterized by degranulation of mast cells, clumping and association of Langerhans cells and lymphocytes. During the second week of treatment there was hyperplasia, hypergranulosis and an increase in the number of membrane coating granules with disorganization of the horny layer both of the epidermis and the follicular epithelium. These changes in the proliferation and the differentiation of keratinocytes resulted in a comedolytic effect. Associated with these epidermal changes there were changes in the dermis with an increased number of mast cells and a decreased number of Langerhans cells.