Related Experiment Video
Updated: May 17, 2025
Inducement and Evaluation of a Murine Model of Experimental Myopia
Published on: January 22, 2019
The interplay between systemic inflammation and myopia: A bidirectional Mendelian randomization and experimental
Zhiqian Huang1, Jitong Zhou1, Shuyu Liu1
1Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; NHC Key laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai 200031, China; Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, China.
Purpose:
Though the pathogenesis of myopia remains unclear, emerging evidence suggests a potential link between the onset of myopia and systemic inflammation. This study aims to elucidate the causal relationships between the two via Mendelian randomization (MR).
Methods:
We utilized genome-wide association study data on circulating inflammatory proteins (n = 14,824), immune cell traits (n = 3757), and myopia (n cases = 4106, n controls = 394,028) for a standard two-sample bidirectional MR analysis, followed by sensitivity analyses employing diverse approaches. The validation of seven inflammatory molecules was conducted through ELISA analysis of 116 plasma samples from a hospital-based cohort, as well as proteomics data from 3310 participants in the UK Biobank cohort.
Results:
Our analysis identified three inflammatory proteins (CXCL9, CXCL11, and T cell surface glycoprotein CD5) and six immune phenotypes, primarily related to T cells, as risk factors for myopia, and IL-5 and eight traits as protective factors. Meanwhile, we observed that myopia may elevate the levels of two inflammatory agents (TNFRSF9 and IL-24) and 12 peripheral immunophenotypes, predominantly associated with T cells and monocytes. Validation analysis in two independent cohorts further corroborated the proinflammatory state in highly myopic patients manifested by significantly elevated plasma levels of CXCL9, CXCL11, and TNFRSF9.
Conclusions:
Our study identified a potential bidirectional causal relationship between systemic immune dynamics and myopia, underscoring the importance of considering myopia in the context of systemic condition. Research is warranted to further identify underlying mechanisms.
Insights
This study reveals a two-way link between systemic inflammation and myopia, identifying specific inflammatory proteins and immune cells involved. These findings suggest myopia should be viewed as a systemic condition requiring further mechanistic research.
Area of Science:
- Ophthalmology
- Immunology
- Genetics
Background:
- The exact causes of myopia are not fully understood.
- Growing evidence suggests a connection between systemic inflammation and myopia development.
Purpose of the Study:
- To investigate the causal relationship between systemic inflammation and myopia using Mendelian randomization (MR).
Main Methods:
- A two-sample bidirectional MR analysis was performed using genome-wide association study data for inflammatory proteins, immune cell traits, and myopia.
- Sensitivity analyses and validation using ELISA and UK Biobank proteomics data were conducted.
Main Results:
- Three inflammatory proteins (CXCL9, CXCL11, CD5) and six immune phenotypes were identified as myopia risk factors.
- Myopia was associated with elevated levels of inflammatory agents (TNFRSF9, IL-24) and specific immune cell traits.
- Validation confirmed elevated plasma levels of CXCL9, CXCL11, and TNFRSF9 in highly myopic individuals.
Conclusions:
- A bidirectional causal relationship exists between systemic immune function and myopia.
- Myopia should be considered within the broader context of systemic health.
- Further research is needed to explore the underlying mechanisms connecting inflammation and myopia.
