Capilliposide A relieved dry age-related macular degeneration through ROS/SIRT1/P53 signaling pathway

Age-related macular degeneration (AMD) is the main cause of vision impairment in the elderly, which still lacks efficient treatment. Capilliposide A (LC-A), a saponin-type anti-inflammation compound extracted from Lysimachia capillipes Hemsl, were used for investigating its anti-AMD effects. The cell viability of LC-A against ARPE-19 cell lines were detected by CCK8 assay. Flow cytometry assay was used for examining ROS accumulation and apoptosis. Dry AMD mice model was constructed by NaIO₃ (i.v.). Then, the anti-AMD effects of LC-A were detected by optical coherence tomography (OCT) assay, electroretinogram (ERG) assay, H&E staining assay and immunofluorescence staining assay. Transcriptome analysis was used to screen the potential signaling pathway of LC-A treatment. Furthermore, Western Blot and immunofluorescence assay were used to verify the signaling pathway in vivo and in vitro. LC-A performed safety against ARPE-19 cell lines (under 25 μM). LC-A also showed significant inhibitory effects against apoptosis and ROS accumulation caused by NaIO₃. Meanwhile, AMD mice model was significantly relieved by LC-A eye-drop treatment. Then, P53 signaling pathways influenced by LC-A was screened out by transcriptome. Results showed that LC-A could inhibit SIRT1/P53 protein expression levels verified by immunofluorescence and Western Blot. These results indicated that LC-A could inhibit apoptosis and ROS accumulation caused dry AMD through SIRT1/P53 signaling pathways, which showed clinical potential for treating senescence-related or SIRT1/P53 mediated AMD patients.