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 ARPE19 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 mu M). 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.