Neovascular age-related macular degeneration (AMD) is described as abnormal angiogenesis in the retina and the leaking of fluid and blood that generates a huge, dark, blind spot in the center of the visual field, causing severe vision loss in over 90% of patients. Bone marrow-derived endothelial progenitor cells (EPCs) contribute to pathologic angiogenesis. Gene expression profiles downloaded from the eyeIntegration v1.0 database for healthy retinas and retinas from patients with neovascular AMD identified significantly higher levels of EPC-specific markers (CD34, CD133) and blood vessel markers (CD31, VEGF) in the neovascular AMD retinas compared with healthy retinas. Melatonin is a hormone that is mainly secreted by the pineal gland, and is also produced in the retina. Whether melatonin affects vascular endothelial growth factor (VEGF)-induced EPC angiogenesis in neovascular AMD is unknown. Our study revealed that melatonin inhibits VEGF-induced stimulation of EPC migration and tube formation. By directly binding with the VEGFR2 extracellular domain, melatonin significantly and dose-dependently inhibited VEGF-induced PDGF-BB expression and angiogenesis in EPCs via c-Src and FAK, NF-κB and AP-1 signaling. The corneal alkali burn model demonstrated that melatonin markedly inhibited EPC angiogenesis and neovascular AMD. Melatonin appears promising for reducing EPC angiogenesis in neovascular AMD.

Osteosarcoma, the most prevalent primary bone tumor, predominantly influences children and adolescents. The pre-metastatic niche (PMN) is a specialized microenvironment that forms before clinically detectable metastatic lesions. Cancer-associated fibroblasts (CAFs) play a crucial function in triggering lung metastasis by coordinating PMN formation in the lung. We found that circRNA_102619, delivered by osteosarcoma-derived extracellular vesicles (EVs), promotes the reprogramming of lung fibroblasts (LFs) into CAFs and PMN formation both in vitro and in vivo. High-throughput protein array analysis revealed that CXCL10, a critical factor secreted by CAFs, drives osteosarcoma proliferation, migration, and resistance to natural killer (NK) cell cytotoxicity. Additionally, circRNA_102619 acts as a sponge for miR-330-3p, thereby controlling CXCL10 production. Importantly, in vivo studies confirmed that osteosarcoma-derived EVs enhance lung PMN formation, promoting osteosarcoma progression and metastasis. Inhibiting osteosarcoma-derived EVs represents a novel strategy to block osteosarcoma progression and metastasis.