722 Combination of retinaldehyde and hydroxylapatite mimics the effects of all-trans retinoic acid in reconstructed human epidermis

The skin functions as a protective barrier from mechanical, chemical, and biological damage. This protection is a direct result of physical properties of the epidermis, composed of a complex balance between epidermal cell cycling (formation, differentiation, desquamation) and protein processing and expression. An imbalance in this system often issues common skin diseases, such as atopic dermatitis (AD) via dysfunction of epidermal differentiation, and Darrier’s disease (DD) via mutations in the gene responsible for encoding calcium transport. A therapeutic strategy capable of improving compromised epidermal/barrier functions has the potential to treat many such skin disorders. Important modulators of epidermal differentiation are concentrations of all-trans retinoic acid (atRA) and calcium gradients. Either an excess or deficiency of atRA and/or calcium degrades the integrity of the skin barrier. atRA and its derivatives, retinoids, cause substantial clinical improvements in patients with barrier function disorders such as DD. However, their use remains limited due to significant adverse effects. An attractive, alternative approach to retinoids is retinaldehyde, the precursor of atRA, due to resulting endogenous synthesis of atRA. Retinaldehyde is highly sensitive to light and oxidation, but can be stabilized for topical use by using minerals such as hydroxylapatite. (HA). A combination of HA and retinaldehyde provides both calcium and endogenous atRA, positively impacting epidermal differentiation. In this study, we have investigated the effects of retinaldehyde alone and in combination with HA on epidermal barrier functionality and gene expression, via transepithelial electrical resistance (TEER) in reconstructed human epidermis (RHE). When in combination, TEER and expression of differentiation markers were modulated similarly to effects via endogenous atRA. HA is expected to potentiate the effect of retinaldehyde on RHEs, resulting in a promising therapeutic strategy for the improvement of the skin barrier function.