Modulating OCA2 Expression as a Promising Approach to Enhance Skin Brightness and Reduce Dark Spots

The oculocutaneous albinism II (<i>OCA2</i>) gene encodes a melanosomal transmembrane protein involved in melanogenesis. Recent genome-wide association studies have identified several single nucleotide polymorphisms within <i>OCA2</i> genes that are involved in skin pigmentation. Nevertheless, there have been no attempts to modulate this gene to improve skin discoloration. Accordingly, our aim was to identify compounds that can reduce <i>OCA2</i> expression and to develop a formula that can improve skin brightness and reduce hyperpigmented spots. In this study, we investigated the effects of <i>OCA2</i> expression reduction on melanin levels, melanosome pH, and autophagy induction through siRNA knockdown. Additionally, we identified several bioactives that effectively reduce <i>OCA2</i> expression. Ultimately, in a clinical trial, we demonstrated that topical application of those compounds significantly improved skin tone and dark spots compared to vitamin C, a typical brightening agent. These findings demonstrate that <i>OCA2</i> is a promising target for the development of efficacious cosmetics and therapeutics designed to treat hyperpigmentation.