Botulinum neurotoxin serotype A inhibited ocular angiogenesis through modulating glial activation via SOCS3.

Autor: Gregg AT; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Wang T; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Szczepan M; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Lam E; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Yagi H; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Neilsen K; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Wang X; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Smith LEH; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA. lois.smith@childrens.harvard.edu., Sun Y; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA. ye.sun@childrens.harvard.edu.
Jazyk: angličtina
Zdroj: Angiogenesis [Angiogenesis] 2024 Nov; Vol. 27 (4), pp. 753-764. Date of Electronic Publication: 2024 Jun 26.
DOI: 10.1007/s10456-024-09935-7
Abstrakt: Background: Pathological angiogenesis causes significant vision loss in neovascular age-related macular degeneration and other retinopathies with neovascularization (NV). Neuronal/glial-vascular interactions influence the release of angiogenic and neurotrophic factors. We hypothesized that botulinum neurotoxin serotype A (BoNT/A) modulates pathological endothelial cell proliferation through glial cell activation and growth factor release.
Methods: A laser-induced choroidal NV (CNV) was employed to investigate the anti-angiogenic effects of BoNT/A. Fundus fluorescence angiography, immunohistochemistry, and real-time PCR were used to assess BoNT/A efficacy in inhibiting CNV and the molecular mechanisms underlying this inhibition. Neuronal and glial suppressor of cytokine signaling 3 (SOCS3) deficient mice were used to investigate the molecular mechanisms of BoNT/A in inhibiting CNV via SOCS3.
Findings: In laser-induced CNV mice with intravitreal BoNT/A treatment, CNV lesions decreased > 30%; vascular leakage and retinal glial activation were suppressed; and Socs3 mRNA expression was induced while vascular endothelial growth factor A (Vegfa) mRNA expression was suppressed. The protective effects of BoNT/A on CNV development were diminished in mice lacking neuronal/glial SOCS3.
Conclusion: BoNT/A suppressed laser-induced CNV and glial cell activation, in part through SOCS3 induction in neuronal/glial cells. BoNT/A treatment led to a decrease of pro-angiogenic factors, including VEGFA, highlighting the potential of BoNT/A as a therapeutic intervention for pathological angiogenesis in retinopathies.
Competing Interests: Declarations Competing interests The authors declare no competing interests. Disclosures Y.S., L.E.H.S, and T.W. are inventors on patent applications filed by Boston Children’s Hospital. The remaining authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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