# Oral Intake of Hydrogen Water Improves Retinal Blood Flow Dysregulation in Response to Flicker Stimulation and Systemic Hyperoxia in Diabetic Mice.
> 水素水の経口摂取が糖尿病マウスの網膜血流調節障害に及ぼす影響：フリッカー刺激および全身高酸素負荷モデルでの検討


## Abstract

This study investigated how hydrogen-rich water (HRW, 0.6–0.8 mM) affects retinal blood flow (RBF) regulation in a type 2 diabetic mouse model. Animals received either HRW or control water from six weeks of age, with RBF assessed via laser speckle flowgraphy at rest and during flicker stimulation and systemic hyperoxia challenges up to 14 weeks. HRW-treated mice showed significantly improved RBF responses beginning at eight weeks, with the benefit sustained throughout the observation period. Immunofluorescence analysis revealed marked reductions in glial fibrillary acidic protein (GFAP) expression, particularly in the outer plexiform layer, indicating attenuated gliosis. The oxidative stress marker 3-nitrotyrosine was also significantly lower in the HRW group. Blood glucose remained elevated but was significantly reduced compared with controls. These findings suggest that HRW may support neurovascular coupling in the diabetic retina by reducing glial activation and oxidative stress.

### Mechanism

HRW is proposed to restore neurovascular coupling in the diabetic retina by suppressing reactive gliosis—evidenced by reduced GFAP expression in the outer plexiform layer—and by decreasing peroxynitrite-mediated oxidative stress, as reflected by lower 3-nitrotyrosine levels.

## Bibliographic

- **Authors**: Sugiyama R, Hanaguri J, Yokota H, Kushiyama A, Kushiyama S, Kikuchi T, et al.
- **Journal**: Transl Vis Sci Technol
- **Year**: 2024 (2024-10-01)
- **PMID**: [39446362](https://pubmed.ncbi.nlm.nih.gov/39446362/)
- **DOI**: [10.1167/tvst.13.10.36](https://doi.org/10.1167/tvst.13.10.36)
- **PMC**: [PMC11512563](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512563/)
- **Study type**: animal study
- **Delivery route**: hydrogen-rich water
- **Effect reported**: positive

## Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident 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)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

---

> **Cite as**: H2 Papers — PMID 39446362. https://h2-papers.org/en/papers/39446362
> **Source**: PubMed PMID [39446362](https://pubmed.ncbi.nlm.nih.gov/39446362/)