Histologic Changes in the Skin of the Rhino Mouse (hrrhhrrh) Induced by Retinoids

Abstract

The effects of four retinoids, all-trans-retinoic acid (RA), 13-cis-retinoic acid (13-cis-RA), aromatic retinoid, and arotinoid ethyl ester ( arotinoid ) were examined on the skin of the rhino mouse. Rhino mouse skin is characterized by the presence of keratin-containing utricles attached to the epidermis, and subcutaneous cysts, both of which are derived from hair follicles. The utricles were examined in horizontal sheets of epidermis, and in vertical histologic sections. After applications of 0.1 ml of 0.1% RA, 0.1% 13-cis-RA, 0.1% aromatic retinoid, or 0.001% arotinoid in acetone to the dorsal skin for 5 days a week for 2 weeks, there was a reduction of utricle diameter to 45%, 52%, 30%, and 31% of acetone-treated controls, respectively. Histologic examination of the epidermis revealed that a dose-dependent hyperplasia and thickening of the epidermis and the stratum granulosum was induced by the retinoids when given at subtoxic doses, being most marked after arotinoid or RA. The thickness of the walls of the utricles also increased with increasing dose of retinoid, paralleling the changes in the epidermis. After doses of 0.1% RA and 0.001% arotinoid , the utricles resembled the hair follicles of hairless mice. Hyperplasia of the epidermis appears to be a primary effect of retinoids or rhino mouse skin. Hyperproliferation of the utricle wall is accompanied by a reduction in the size of the utricle lumen, preceding eventual differentiation of the utricles to normal-looking pilar units.

Comedolytic Effect of Topical Retinaldehyde in the Rhino Mouse Model

“…On all the parameters studied, RAL had the same activity as RA; further studies on dose-dependent activity would be interesting to perform. These effects are those of retinoids, due to an induction of epidermal cell proliferation which is specific to retinoid treatment and well known in the rhino mouse model [5]. …”

Real-TimeReflectance Confocal Microscopy, a Noninvasive Tool for in vivo Quantitative Evaluation of Comedolysis in the Rhino Mouse Model

“…The rhino mouse has been used as an animal model in experiments of keratolytic agents such as retinoids, because of the similarity of its horn-filled utriculi to comedones [3,5] . Retinoids are known to induce comedolysis and epidermal thickening.…”

“…Mezick et al [4] reported a method of examining sheets of rhino mouse skin in a horizontal approach. Ashton et al [5] used this method for measuring the diameter of utriculi. The results showed that utricular count is different if the horizontal or the vertical approach is used.…”

“…Kligman and Kligman [3] reported that retinoids topically applied to rhino mouse skin lead to transformation of horn-filled utriculi into normal follicular structures, and suggested that evaluation of changes in utriculus size could be used to assess the relative potency of retinoids. Since then, many studies have used the rhino mouse model to investigate the comedolytic activity of retinoids [4][5][6][7][8] . Kligman and Kligman [3] used routine histology with vertical sections, while others evaluated sheets of rhino mouse skin horizontally to overcome the limitations of vertical sections [4,5] .…”

“…Since then, many studies have used the rhino mouse model to investigate the comedolytic activity of retinoids [4][5][6][7][8] . Kligman and Kligman [3] used routine histology with vertical sections, while others evaluated sheets of rhino mouse skin horizontally to overcome the limitations of vertical sections [4,5] . Bouclier et al [9] introduced image analysis using a semiautomatic MOP Videoplan system (Kontron) equipped with a microscope-coupled TV camera.…”