Therapeutic Modulation of the Nox2-Hv1-ROS Axis by Botulinum Neurotoxin A Confers Protection Against CoCl₂-Induced Retinal Hypoxic Injury.

ABSTRACT: Neuroinflammation and oxidative stress are key drivers of various ocular diseases. Experimental hypoxia, modeled using cobalt chloride (CoCl₂), induces hypoxia-inducible factor 1-alpha (HIF-1α) stabilization, mitochondrial dysfunction, and excessive reactive oxygen species (ROS) production, primarily via the NADPH oxidase 2 (Nox2)-voltage-gated proton channel Hv1 axis. Although Botulinum neurotoxin type A (BoNT/A) is classically recognized for SNAP-25 cleavage, recent studies suggest broader anti-inflammatory and neuroprotective effects. We evaluated BoNT/A in R28 retinal precursor cells and ex vivo retinal explants subjected to CoCl₂-induced hypoxic stress. BoNT/A pretreatment attenuated CoCl₂-induced upregulation of HIF-1α, Hv1, Nox2, NOD-like receptor pr

SUBMITTER: Lee HJ 

PROVIDER: S-EPMC12608730 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature