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Chronic topical application of all-trans-retinoic acid in man does not affect corneocyte surface area
S M Robinson1, M Poncet, J Ferracin
1Centre de Pharmacologie Clinique, Appliquée à la Dermatologie (CPCAD), Nice, France.
Abstract:
The potential therapeutic activity of topically applied novel analogues of retinoic acid is currently measured in many different animal models. In most cases, the technique used is invasive and biopsy specimens are required. Furthermore, efficacy in these models is not a guarantee of success in treatment of humans. Therefore, predictive human pharmacology tests are required in order to quantify a retinoid effect on human skin before conducting large clinical trials. The aim of this study was to determine whether changes in corneocyte surface area could be used as a predictive measure for the efficacy of topical retinoids in man. Topical applications of all-trans retinoic acid gel (Aberel), salicylic acid gel and the gel vehicle were made once daily for 4 weeks to skin of the lumbar region of healthy human volunteers. Corneocytes were recovered from these three treated zones as well as from one zone of untreated skin, and their surface areas were measured by image analysis using a MOP-Videoplan. The results showed that at no point during the 4 weeks of daily application to healthy human skin was there a statistically significant difference in the surface area of corneocytes recovered from Aberel, salicylic acid-, vehicle-treated or untreated sites. No specific effect of retinoic acid could be detected. However, although no between-treatment differences were found, significant cyclical changes in the mean surface areas with respect to baseline were observed.
Insights
Measuring corneocyte surface area changes is not a reliable predictive measure for topical retinoid efficacy in humans. This study found no significant differences in corneocyte size with all-trans retinoic acid treatment.
Area of Science:
- Dermatology
- Pharmacology
- Skin Biology
Background:
- Topical retinoids show therapeutic potential but require invasive animal models for efficacy testing.
- Animal model efficacy does not always translate to human treatment success.
- Predictive human pharmacology tests are needed to assess retinoid effects before clinical trials.
Purpose of the Study:
- To evaluate corneocyte surface area changes as a predictive measure for topical retinoid efficacy in humans.
- To determine if all-trans retinoic acid impacts corneocyte size in healthy human skin.
Main Methods:
- Healthy volunteers applied all-trans retinoic acid gel, salicylic acid gel, or vehicle daily for 4 weeks.
- Corneocytes were collected from treated and untreated skin sites.
- Corneocyte surface area was measured using image analysis (MOP-Videoplan).
Main Results:
- No statistically significant differences in corneocyte surface area were observed between Aberel, salicylic acid, vehicle, or untreated sites.
- All-trans retinoic acid did not demonstrate a detectable effect on corneocyte surface area.
- Significant cyclical changes in mean corneocyte surface area over time were noted, independent of treatment.
Conclusions:
- Corneocyte surface area measurement is not a suitable predictive biomarker for topical retinoid efficacy in human skin.
- Further research is needed to identify reliable non-invasive biomarkers for retinoid drug development.