Quantification of Epidermal Histological Changes Induced by Topical Retinoids and CD271 in the Rhino Mouse Model Using a Standardized Image Analysis Technique

Abstract

The rhino mouse has been used as an experimental model to screen topically active comedolytic agents. Adult rhino mice were treated on the back once daily for 5 consecutive days per week during 3 weeks. Skin histological preparations were analyzed by image analysis techniques to quantify the number of epidermal comedones, comedo profile and epidermal thickness. Using both a negative (treated with acetone) and a positive (treated with Aberel® gel 0.025%) control group of animals in all experiments conducted over a period of about 3 years, we defined the upper and lower limit of acceptability of the results. Topical treatment with an acetone solution of all-trans retinoic acid (0.01, 0.03, 0.1 %) and 13-cis-retinoic acid (0.1 %) induced comedolysis and a marked increase in epidermal thickness. Commercial preparations of all-trans retinoic acid (Aberel® lotion, gel and cream, Retin A® cream, Retacnyl cream) presented a similar comedolytic activity. However, the epidermal thickening was higher with Retin A and weaker with Retacnyl. CD271, a new modulator of cell differentiation, applied either in acetone solution (0.01, 0.1 %) or in lotion, gel or cream formulations (0.1 %) also demonstrated a marked activity (i.e. comedolysis and epidermal thickening). These data confirm that the rhino mouse model can be used to assay drugs applied either in solvent or in topical formulations. Activity in this model compares favorably with published clinical observations in the treatment of acne.

Retinoid pathway and cancer therapeutics

“…13-cis RA noticeably reduces the production of sebum and shrinks the sebaceous glands [90]. It stabilizes keratinization and prevents comedones formation [91, 92]. The exact mechanism of action is unknown.…”

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

“…It was suggested that this might happen because utriculi become smaller in treated skin so that fewer are sectioned in vertical cuts. Bouclier et al [9] and Fort-Lacoste et al [10] used an image analysis technique to quantify the number of utriculi based on regular histology. Although these previous studies yielded valid results, they all used invasive methods.…”

“…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. Fort-Lacoste et al [10] used an Axiomat Zeiss microscope, which examines vertical sheets and provides more accurate measurements.…”

A Review of Adapalene in the Treatment of Acne Vulgaris

“…This inhibition of keratinocyte differentiation and proliferation is responsible for adapalene's comedolytic effect. In an in vivo study, adapalene's ability to reduce comedone formation was demonstrated by a 50 -60% reduction in comedone counts compared with vehicle [9].…”