# Molecular hydrogen promotes retinal vascular regeneration and attenuates neovascularization and neuroglial dysfunction in oxygen-induced retinopathy mice.
> 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


## Abstract

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.

### Mechanism

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.

## Bibliographic

- **Authors**: Guo Y, Qin J, Sun R, Hao P, Jiang Z, Wang Y, et al.
- **Journal**: Biol Res
- **Year**: 2024 (2024-06-24)
- **PMID**: [38915069](https://pubmed.ncbi.nlm.nih.gov/38915069/)
- **DOI**: [10.1186/s40659-024-00515-z](https://doi.org/10.1186/s40659-024-00515-z)
- **PMC**: [PMC11194953](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194953/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 3–4%

## Delivery context

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.

## Safety notes

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:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 38915069. https://h2-papers.org/en/papers/38915069
> **Source**: PubMed PMID [38915069](https://pubmed.ncbi.nlm.nih.gov/38915069/)