O07 Lower doses of retinol facilitate cell proliferation and epidermal thickening in photoaged skin

Abstract Introduction and aims Chronic exposure to solar ultraviolet radiation leads to cutaneous hypertrophic photoageing which clinically manifests as wrinkles, skin laxity and hyperpigmentation. This photoaged phenotype is underscored by a remodelled cutaneous microenvironment including epidermal thinning and rete ridge flattening. We have previously shown that cosmeceutical formulations of 0.3% and 1% retinol can effectively induce epidermal thickening and keratinocyte proliferation. However, these concentrations require careful usage to limit potential irritancy issues, highlighting a need to explore the benefits of lower dose retinol for daily skincare. Therefore, we compare the efficacy of lower doses of retinol in facilitating epidermal thickness and proliferation in photoaged skin, as this currently remains unknown. Methods Using the in vivo Manchester Patch Test Assay, test substances (vehicle and retinol at concentrations of 0.025%, 0.05%, 0.1% and 1%) were applied under occlusion to extensor forearms of healthy but photoaged volunteers (three men, three women; age range 66–86 years) for 12 days. Resultant skin biopsies were processed for histological assessment of epidermal thickness and keratinocyte proliferation. Results Epidermal thickness was significantly increased with 0.025% (P < 0.05), 0.05%, 0.1% and 1% (all P < 0.01) retinol treatment, compared with baseline or vehicle. Immunofluorescence staining of the proliferation marker Ki67 identified elevated keratinocyte proliferation following retinol treatment (P < 0.05 for 0.025%, 0.05% and 1%) compared with baseline. Although Ki67 expression in the 0.1% retinol treatment was elevated, significance was not achieved compared with baseline. However, compared with the vehicle, all retinol concentrations significantly increased Ki67 expression (P < 0.05). Clinically, 50% of volunteers showed an erythemal irritancy response to 1% retinol only. Conclusions We established that lower doses of retinol are capable of inducing keratinocyte proliferation and epidermal thickening without irritancy issues. Therefore, long-term effective treatment of photoaged skin with low-dose retinol products may be the preferred choice for individuals where retinol sensitivity has previously been an issue.