Combining large‐spot low‐fluence 1064‐nm and fractional 1064‐nm picosecond lasers for promoting protective melanosome autophagy via the PI3K/Akt/mTOR signalling pathway for the treatment of melasma

Abstract Melasma is a common condition of hyperpigmented facial skin. Picosecond lasers are reported to be effective for the treatment of melasma. We aimed to identify the most effective therapeutic mode and elucidate the potential molecular mechanisms of picosecond lasers for the treatment of melasma. Female Kunming mice with melasma‐like conditions were treated using four different picosecond laser modes. Concurrently, in vitro experiments were conducted to assess changes in melanin and autophagy in mouse melanoma B16‐F10 cells treated with these laser modes. Changes in melanin in mouse skin were detected via Fontana–Masson staining, and melanin particles were evaluated in B16‐F10 cells. Real‐time polymerase chain reaction and western blotting were used to analyse the expression levels of melanosome and autophagy‐related messenger ribonucleic acid (mRNA) and proteins. A combination of large‐spot low‐fluence 1064‐nm and fractional 1064‐nm picosecond lasers resulted insignificant decreases in melanin as well as in mRNA and protein expression of melanin‐synthesizing enzymes (TYR, TRP‐1 and MITF). This combination also led to increased expression of the autophagy‐related proteins, Beclin1 and ATG5, with a marked decrease in p62 expression. Intervention with the PI3K activator, 740 Y‐P, increased TYR, TRP‐1, MITF, p‐PI3K, p‐AKT, p‐mTOR and p62 expression but decreased the expression of LC3, ATG5 and Beclin1. A combination of large‐spot low‐fluence 1064‐nm and fractional 1064‐nm picosecond lasers proved more effective and safer. It inhibits melanin production, downregulates the PI3K/AKT/mTOR pathway, enhances melanocyte autophagy and accelerates melanin metabolism, thereby reducing melanin content.