The Anti-Inflammatory Effect of Hydrogen Gas Inhalation and Its Influence on Laser-Induced Choroidal Neovascularization in a Mouse Model of Neovascular Age-Related Macular Degeneration

• Published in: International journal of molecular sciences 2021-11, Vol.22 (21), p.12049
• Main Authors: Liang, I-Chia, Ko, Wen-Chin, Hsu, Yu-Jou, Lin, Yi-Ru, Chang, Yun-Hsiang, Zong, Xv-Hui, Lai, Pei-Chen, Chang, Der-Chen, Hung, Chi-Feng
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Angiogenesis; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - pharmacology; Angiography; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Antioxidants; Atrophy; Blindness; Choroidal Neovascularization - etiology; Choroidal Neovascularization - pathology; Choroidal Neovascularization - therapy; Disease Models, Animal; Fluorescein Angiography; Fluorescence; Fundus Oculi; Gases; Gene expression; Growth factors; Hydrogen; Hydrogen - administration & dosage; Hydrogen - pharmacology; Hypoxia; Hypoxia-inducible factor 1; Hypoxia-inducible factor 1a; Hypoxia-inducible factors; Inflammation; Inhalation; Ischemia; Lasers; Leakage; Macular degeneration; Macular Degeneration - etiology; Macular Degeneration - pathology; Macular Degeneration - therapy; Metabolism; Mice; Mice, Inbred C57BL; Oxidative stress; Phosphorylation; Respiration; Retina; Risk factors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vascular endothelial growth factor; Vascularization; Wet Macular Degeneration - etiology; Wet Macular Degeneration - pathology; Wet Macular Degeneration - therapy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222112049

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. Choroidal neovascularization (CNV) is the major pathologic feature of neovascular AMD. Oxidative damages and the ensuing chronic inflammation are representative of trigger events. Hydrogen gas (H ) has been demonstrated as an antioxidant and plays a role in the regulation of oxidative stress and inflammation. This experiment aimed to investigate the influence of H inhalation on a mouse model of CNV. Laser was used to induce CNV formation. C57BL/6J mice were divided into five groups: the control group; the laser-only group; and the 2 h, 5 h, and 2.5 h/2.5 h groups that received laser and H inhalation (21% oxygen, 42% hydrogen, and 37% nitrogen mixture) for 2 h, 5 h, and 2.5 h twice every day, respectively. The severity of CNV leakage on fluorescence angiography showed a significant decrease in the H inhalation groups. The mRNA expression of hypoxia-inducible factor 1 alpha and its immediate downstream target vascular endothelial growth factor (VEGF) showed significant elevation after laser, and this elevation was suppressed in the H inhalation groups in an inhalation period length-related manner. The mRNA expression of cytokines, including tumor necrosis factor alpha and interlukin-6, also represented similar results. H inhalation could alleviate CNV leakage in a laser-induced mouse CNV model, and the potential mechanism might be related to the suppression of the inflammatory process and VEGF-driven CNV formation.