Didierjean et al (p. 714) show that, in mouse skin, topical retinaldehyde is transformed in vivo into small amounts of all-trans retinoic acid sufficient to induce biologic effects similar to those resulting from topical application of all-trans retinoic acid itself in much higher concentration. The same group recently proposed retinaldehyde for topical use in humans. Retinaldehyde is a natural metabolite of beta-carotene and retinol. As retinaldehyde does not bind to retinoic acid receptors, its biologic activity should result from enzymatic transformation by keratinocytes into ligands for these receptors (i.e. all-trans and 9-cis retinoic acid). To test this possibility, the authors used the tail skin model and analyzed by high performance liquid chromatography the type and amounts of skin retinoids and characterized the biological effects produced by topical retinaldehyde and all-trans retinoic acid as comparison. They demonstrate that murine skin in vivo transforms retinaldehyde into all-trans retinoic acid. As the authors anticipated, retinaldehyde applied at 0.05% was unable to load the skin with as much all-trans retinoic acid as that resulting from topical application of 0.05% all-trans retinoic acid; nevertheless, topical retinaldehyde induced differentiation and proliferating (retinoid) activities similar to those produced by all-trans retinoic acid in this model. This study supports the concept of using precursors such as retinaldehyde to deliver retinoid activity in the skin; it suggests that the bulk of all-trans retinoic acid applied onto the skin does not reach molecular targets of retinoid activities within the cell.
Journal of Investigative Dermatology