水素ガス吸入が酸素誘発網膜症マウスにおける網膜血管再生・新生血管抑制・神経グリア保護に及ぼす影響
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, and current interventions carry notable complication risks. This study examined the effects of 3–4% hydrogen gas inhalation in oxygen-induced retinopathy (OIR) mice (wild-type and Nrf2-knockout), assessing vascular obliteration, pathological neovascularization, and neuroglial changes. Hydrogen inhalation did not impair physiological angiogenesis but reduced vaso-obliteration and abnormal vessel growth. Retinal astrocyte density and morphology were preserved, and microglial activation—particularly in neovascular zones—was diminished. Mechanistically, hydrogen promoted Nrf2 activation, suppressed Dll4-driven Notch signaling, and modulated HIF-1α/VEGF pathways. In vitro experiments using HUVECs under hypoxia corroborated these findings, showing enhanced proliferation alongside reduced ROS levels via Nrf2 and Dll4/Notch pathway regulation. These results suggest that molecular hydrogen exerts protective effects on retinal vasculature and glia in OIR through coordinated Nrf2-Notch and HIF-1α/VEGF signaling.
Hydrogen activates Nrf2 to reduce reactive oxygen species and suppresses Dll4-induced Notch signaling to inhibit pathological neovascularization, while modulating HIF-1α/VEGF pathways to support physiological retinal revascularization.
For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.
See also:
https://h2-papers.org/en/papers/38915069