Choroidal neovascularization induced by age-related macular degeneration and retinal neovascularization induced by diabetic retinopathy—two leading causes of blindness—are often treated using antibodies targeting vascular endothelial growth factor (VEGF). Here we report a strong association between inflammation and high VEGF expression in aqueous humour samples from patients with choroidal or retinal neovascularization, and show that intravitreally injected exosomes derived from regulatory T cells and conjugated with an anti-VEGF antibody via a peptide linker that is cleavable by matrix metalloproteinases markedly suppressed ocular neovascularization in mouse and non-human primate models of choroidal neovascularization. The engineered exosomes, which selectively accumulate in the neovascularization lesions, could be adapted for other combination therapies of therapeutic antibodies and anti-inflammatory cargo.
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The main data supporting the results in this study are available within the paper and its Supplementary Information. Source data for the figures are available as Supplementary Information and also at figshare: https://figshare.com/articles/dataset/Source_Data_xlsx/14401208. The RNA-sequencing data are available at the NCBI BioProject under accession PRJNA721185. Source data are provided with this paper.
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This work was supported by the National Natural Science Foundation of China (82070948, U2001224), the Beijing Chaoyang 1351 talent training programme (CYXX-2017-21) and the Scientific Research Program of Beijing Municipal Commission of Education (KM202010025020).
The authors declare no competing interests.
Peer review information Nature Biomedical Engineering thanks Nicholas Agard and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Tian, Y., Zhang, F., Qiu, Y. et al. Reduction of choroidal neovascularization via cleavable VEGF antibodies conjugated to exosomes derived from regulatory T cells. Nat Biomed Eng 5, 968–982 (2021). https://doi.org/10.1038/s41551-021-00764-3