Background: The damage caused by pathological angiogenesis to visual function is grievous. Retinol-binding protein 3 (RBP3) demonstrates an inverse relationship with diabetic retinopathy (DR) progress and suppresses pathological retinal angiogenesis under hyperglycemic conditions. However, the impact of externally administered RBP3 in such pathological retinal angiogenesis remains undefined. This research explores how intravitreally delivered RBP3-loaded exosomes (RBP3-Exo) curtail abnormal retinal vessel growth.

Methods: We generated RBP3-Exo with safety and good biocompatibility using plasmid transfection technology. The anti-angiogenic effect of RBP3-Exo was evaluated in vitro through cell proliferation, sprouting assays, and other experiments. Using an oxygen-induced retinopathy (OIR) model, we administered exosomes intravitreally and conducted subsequent staining assays to evaluate angiogenic activity in vivo. RNA-seq was conducted, which revealed that its main target pathway is the DNA replication pathway, and this was verified by Real-time quantitative polymerase chain reaction (qPCR) and Western blot.

Results: Results indicate that RBP3-loaded exosomes markedly restrain endothelial cell proliferation and sprouting in laboratory settings. In OIR mice, they also diminish both avascular retinal zones and pathological neovascular tuft formation. Mechanistically, RBP3-loaded exosomes may achieve these effects by interfering with DNA replication processes.

Conclusion: In conclusion, RBP3-Exo potently suppress pathological retinal angiogenesis, positioning them as a compelling therapeutic candidate for ocular neovascular diseases.