LAUSR

BACKGROUND Decline of lymphatic vessel (LV) density and function in intrinsically aged skin leads to harmful substances accumulation and fluid imbalance. Whether it will be improved by low dose ALA-PDT needs to be investigated. AIMS To investigate the effect of low dose ALA-PDT on remodeling LVs in intrinsically aged skin. METHODS Low dose ALA-PDT with 3 sessions were applied on the dorsal skin of intrinsically aged SKH-1 mice (15 months old). Skin biopsies were obtained from young mice (Young-control), intrinsically aged mice before PDT (Old-pre-PDT), and after PDT at different time points (Old-PDT-24h, Old-PDT-1w, Old-PDT-4w), and skin phenotypes were evaluated by dermoscopy. The structure of LVs and extracellular matrix were evaluated via immunofluorescence staining and HE. The drainage function of LVs was evaluated by Evans Blue assay in vivo. The expression of Calcium-binding EGF domain-containing protein 1 (CCBE1), VE-cadherin, and the activation of VEGF-C/VEGFR3 signaling pathway were evaluated by ELISA and Western Blot. RESULTS The density of LVs decreased and the lymphatic clearance was significantly delayed in aged skin. Low dose ALA-PDT increased the density of LVs and collagen. The clearance of Evans Blue assay showed the drainage function of LVs was improved after PDT treatments in vivo. The VE-cadherin and VEGF-C/VEGFR3 pathway up-regulated in intrinsically aged skin after ALA-PDT treatments. CONCLUSIONS LVs in intrinsically aged skin were remodeled and their function were restored by low dose ALA-PDT via up-regulating the VEGF-C/VEGFR3 pathway.