Apolipoprotein C3 Promotes Retinal Angiogenesis via the MYC Pathway in Hypoxia

PURPOSE: The aim of this study was to investigate the function of Apolipoprotein C3 (APOC3) in the retina under hypoxic conditions. METHODS: The quantitative expression of APOC3 in the aqueous humor of patients with diabetic retinopathy (DR) was determined using proteomics datasets. A multiplex immunoassay was used to measure APOC3 levels in the serum of patients with DR. Western blotting and enzyme-linked immunosorbent assays were used to assess APOC3 expression in the liver, duodenum, retina, and serum of db/db mice and oxygen-induced retinopathy (OIR) mice, as well as in human retinal microvascular endothelial cells (hRMECs) exposed to high glucose, hypoxia, or both. Cell proliferation, migration, and tube formation assays were conducted in hRMECs treated with recombinant APOC3 (r-APOC3), hypoxia, or both. RNA sequencing and inhibition assays were performed to explore the pathways associated with r-APOC3 and hypoxia stimulation. RESULTS: APOC3 expression was significantly increased in the aqueous humor and serum of patients with DR, as well as in the liver, duodenum, serum, and retina of db/db and OIR mice, but did not change markedly in either the hRMECs or their conditioned media under given conditions. r-APOC3 combined with hypoxia significantly enhanced the proliferation, migration, and tube formation of hRMECs, promoting the upregulation of MYC, VEGFA, and IL6. Inhibition of MYC expression reduced VEGFA and IL6 levels and alleviated the phenotypic changes in hRMECs treated with r-APOC3 and hypoxia. CONCLUSION: activation of the MYC pathway under hypoxic conditions, suggesting its involvement in DR.