Summary
The histological and ultrastructural effects following 3 weeks' topical treatment with two agents (all-trans retinoic acid and a new synthetic retinoid-like substance, CD271) were evaluated on the epidermis and the epithelial wall of the pseudocomedones in rhino mouse skin. The comedolytic effects of these drugs were similar, and consisted of a reduction of the utricular diameter, with normalization of follicular units. Morphological examinations revealed a hyperplastic response with an increase in the number of cell layers of both epidermis and follicular epithelium, and modifications in keratinocyte differentiation. Ultrastructural changes in the epidermis and epithelial wall were observed mainly in the granular and horny layers, with increased desquamation, and a decrease in the cohesiveness of corneocytes. During the first week of treatment, some cutaneous toxic effects were noticed, but they normalized within two weeks. On the other hand, a fine granular material persisted in the intercellular spaces. It is confirmed that the skin of the rhino mouse is a good model for the evaluation of the comedolytic effects of drugs. Moreover, it reveals the specific effects of retinoids on epidermal differentiation. We have demonstrated that topically applied CD271 induces modifications similar to those obtained with all-trans retinoic acid. It is thus concluded that CD271 is a potentially effective anti-acne agent.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ashton R, Connor M, Lowe N (1984) Histologic changes in the skin of the rhino mouse (hrrhhrrh) induced by retinoÏds. J Invest Dermatol 82:632–635
Bernerd F, Bouclier M, Dange M, Rossio P, Hensby C (1989) Morphological changes induced by repeated topical application of retinoids to hairless rats. In: Reichert U, Shroot B (eds) Pharmacology and the skin. Pharmacology of retinoids in the skin. Karger, Basel, pp 139–140
Bonne C, Zezolia F, Secchi J, Saurat J (1981) A new model for the assay of comedolytic activity. Int J Cosm Sci 3:23–28
Bouclier M, Dange M, Burg G, Delamadeleine F, Rossio P, Fouque MC, Hensby C (1989) Retinoid-induced dose-related hypervitaminosis A, epidermal hyperplasia and tail morphological changes in the mouse: an assay to evaluate biological indexes of activity. In: Reichert U, Shroot B (eds) Pharmacology and the skin. Pharmacology of retinoids in the skin. Karger, Basel, pp 136–138
Brown W, Habowsky J (1979) Comparative ultrastructure and cytochemistry of epidermal responses to tape stripping, ethanol and vitamin A acid in hairless mice. J Invest Dermatol 73:203–206
Chatelus A, Caron D, Shroot B, Eustache J, Hensby C (1989) Structure activity relationship between different retinoids using the topical rhino mouse comedolytic model. In: Reichert U, Shrott B (eds) Pharmacology and the skin. Pharmacology of retinoids in the skin. Karger, Basel, pp 144–148
Christophers E, Braun-Falco O (1968) Stimulation of epidermal DNA synthesis through vitamin A acid. Arch Klin Exp Dermatol 232:427–433
Davies R, Austin W, Logani M (1971) The rhino mutant mouse as an experimental tool. Trans NY Acad Sci 33:680–693
Dingle JT (1961) Studies of the mode of action of excess of vitamin A. III. Release of a bound protease by action of vitamin A. Biochem J 79:509–512
Elias P (1986) Epidermal effects of retinoids: supramolecular observations and clinical implications. J Am Acad Dermatol 15:797–809
Ellis C, Gold R, Grekin R, Swanson N, Anderson T, Voorhees J (1981) Retinoid-stimulated material in psoriasic epidermis during Ro 10-9359 therapy. In: Orfanos CE, Braun-Falco O, Farber EM, Grupper Ch, Polano MK, Schuppli R (eds) Retinoids. Advances in basic research and therapy. Springer, Berlin Heidelberg New York, pp 93–98
Hensby C, Cavey D, Bouclier M, Chatelus A, Algate D, Eustache J, Shroot B (1989) The in vivo and in vitro antiinflammatory activity of CD271, a new retinoid-like modulator of cell differentiation. In: Reichert U, Shroot B (eds) Pharmacology and the skin. Pharmacology of retinoids in the skin. Karger, Basel, pp 160–162
Howard A (1940) “Rhino”, an allele of hairlessness in the house mouse. J Hered 31:467–470
Kanerva L, Lauharanta J, Niemi KM, Lassus A (1981) Fine structure of the intercellular space of psoriatic epidermis during retinoid (RO 10.9359) and retinoid-PUVA treatment. Acta Derm Venereol (Stockh) 61:319–328
King I, Tabiowo A (1981) The effect of all-trans retinoic acid on the synthesis of epidermal cell-surface-associated carbohydrates. Biochemistry 194:341–350
Kligman L, Kligman A (1979) The effect on rhino mouse skin of agents which influence keratinization and exfoliation. J Invest Dermatol 73:354–358
Mann J (1971) Hair loss and cyst formation in hairless and rhino mutant mice. Anat Rec 270:465–500
Marcelo C, Madison K (1984) Regulation of the expression of epidermal keratinocyte proliferation and differentiation by vitamin A analogs. Arch Dermatol Res 276:381–389
Nomura H, Hachisuka H, Sasai Y (1985) Cytofluorometric study of epidermal cell proliferation induced by oral administration of aromatic retinoid. J Dermatol 112:429–435
Papa C (1976) Scanning electron microscopic study of tretinoin (vitamin A acid) acne therapy. Cutis 17:575–580
Reaven E, Cox A (1965) Histidine and keratinization. J Invest Dermatol 45:422–431
Schultz-Ehrenburg U, Orfanos CE (1981) Light and electron microscopic changes under oral retinoid treatment. In: Orfanos CE, Braun-Falco O, Farber EM, Grupper Ch, Polano MK, Schuppli R (eds) Retinoids. Advances in basic research and therapy. Springer, Berlin Heidelberg New York, pp 85–92
Shroot B (1989) A strategy for discovery of new retinoid-like substances. In: Reichert U, Shroot B (eds) Pharmacology and the skin. Pharmacology of retinoids in the skin. Karger, Basel, pp 270–277
Tsambaos D, Mahrle G, Orfanos CE (1980) Epidermal changes induced by oral excess of aromatic retinoid in guinea pigs. Arch Dermatol Res 267:141–152
Van Scott E (1972) Experimental animal integumental models for screening potential dermatologic drugs. In: Montagna W, Van Scott E, Staughton R (eds) Pharmacology and the skin. Appleton Century Crofts, New York, pp 523–533
Wolff H, Plewig G, Braun-Falco O (1975) Ultrastructure of human sebaceous follicles and comedones following treatment with vitamin A acid. Acta Derm Venereol Suppl (Stockh) 74:99–110
Woo-Sam PC (1979) The effect of vitamin A acid on experimentally induced comedones: an electron microscopic study. Br J Dermatol 100:267–276
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bernerd, F., Ortonne, J.P., Bouclier, M. et al. The rhino mouse model: the effects of topically applied all-trans retinoic acid and CD271 on the fine structure of the epidermis and utricle wall of pseudocomedones. Arch Dermatol Res 283, 100–107 (1991). https://doi.org/10.1007/BF00371617
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00371617