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.

I-Chia Liang,Wen-Chin Ko,Pei-Chen Lai,Yu-Jou Hsu,Chi-Feng Hung,Yi-Ru Lin,Der-Chen Chang,Xv-Hui Zong,Yun-Hsiang Chang

doi:10.3390/ijms222112049

Abstract

Background: 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 (H2) 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 H2 inhalation on a mouse model of CNV. Methods: 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 H2 inhalation (21% oxygen, 42% hydrogen, and 37% nitrogen mixture) for 2 h, 5 h, and 2.5 h twice every day, respectively. Results: The severity of CNV leakage on fluorescence angiography showed a significant decrease in the H2 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 H2 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. Conclusion: H2 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.

Highlights

Age-related macular degeneration (AMD), the leading cause of blindness in elderly people aged over 60, is estimated to have an increasing prevalence globally as a consequence of exponential population growth, increase in life expectancy, and falling death rates [1,2,3]
The mRNA expression of HIF-1α and vascular endothelial growth factor (VEGF) could be successfully inhibited by hydrogen gas inhalation in an inhalation time-related manner
Our results revealed that not just VEGF but the upstream translation factor HIF could be inhibited by hydrogen gas inhalation

Summary

Introduction

Age-related macular degeneration (AMD), the leading cause of blindness in elderly people aged over 60, is estimated to have an increasing prevalence globally as a consequence of exponential population growth, increase in life expectancy, and falling death rates [1,2,3]. There is a higher prevalence of AMD in Europeans than in Asians and Africans, while there is no difference between Asians and Africans. AMD stems from accumulation of drusen, the lipoprotein-rich deposits underneath retinal pigment epithelium (RPE) with pigmentary changes and/ or thickened overlying Bruch’s membrane. Advanced AMD is classified to be of the dry (atrophic) or wet (neovascular) type. Advanced dry AMD is characterized by progressive atrophic changes in the RPE and overlying neurosensory retina with an eventual development of geographic atrophy. The AREDS study showed a reduction in the progression from intermediate AMD to advanced AMD with a daily formula of 500 mg vitamin C, 80 mg zinc, 400 IU vitamin E, 2 mg copper, and 15 mg beta carotene. Lifestyle modification is recommended to inhibit the progression of AMD [12,13]

Results

Discussion

Conclusion