{Reference Type}: Journal Article
{Title}: Botulinum neurotoxin serotype A inhibited ocular angiogenesis through modulating glial activation via SOCS3.
{Author}: Gregg AT;Wang T;Szczepan M;Lam E;Yagi H;Neilsen K;Wang X;Smith LEH;Sun Y;
{Journal}: Angiogenesis
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 26
{Factor}: 10.658
{DOI}: 10.1007/s10456-024-09935-7
{Abstract}: <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.