Related Experiment Video
Updated: Sep 14, 2025
Induction of Ocular Surface Inflammation and Collection of Involved Tissues
Published on: August 4, 2022
Natural active ingredients targeted inflammatory cytokines and major blinding eye diseases: a two-sample Mendelian
Ying Shao1, Yicheng Lu2, Yue Gu3
1Department of Ophthalmology, Kunshan Rehabilitation Hospital, Suzhou, Jiangsu, China.
Objectives:
Previous studies have reported that a few inflammatory cytokines have associations with ocular diseases. The objective of this study is to explore the causal relationship between 41 inflammatory cytokines and five ocular diseases using Mendelian randomization (MR) method and study the interaction between five natural active ingredients and inflammatory cytokines through molecular docking.
Methods:
The two-sample MR study employed genetic variances related to age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), myopia, and cataract. These variances were sourced from a comprehensive, publicly accessible genome-wide association study (GWAS). Additionally, inflammatory cytokines were derived from a GWAS summary that included 8,293 healthy individuals. The study primarily used the inverse variance weighted (IVW) method to investigate the causality between exposures and outcomes. To further bolster the final results, a variety of methods were concurrently used, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. A protein-protein interaction (PPI) network was constructed, and corresponding protein interaction relationships were analyzed utilizing the STRING database. Molecular docking served as an evaluation tool, confirming the binding between components and targets. This process was performed using AutoDock and PyMOL software.
Results:
The results indicated that IL-18 (OR: 1.134, 95% CI: 1.009-1.275, P = 0.034) and PDGF-BB (OR: 0.804, 95% CI: 0.678-0.954, P = 0.012) had protective effect on AMD; Genetically predicted RANTES had protective effect on glaucoma (OR: 0.886, 95% CI: 0.810-0.969, P = 0.008); IL-10 had protective effect on DR (OR: 0.871, 95% CI: 0.759-0.999, P = 0.048); GROa may be associated with increased myopia risk (OR: 1.230, 95% CI: 1.046-1.446, P = 0.012); Eotaxin (OR: 1.089, 95% CI: 1.018-1.165, P = 0.013), FGF2 (OR: 1.183, 95% CI: 1.004-1.393, P = 0.045) and GROa (OR: 1.053, 95% CI: 1.000-1.109, P = 0.049) were associated with increased cataract risk, while IL-1RA may be associated with decreased cataract risk. PPI network showed GROa, FGF2, IL-18, IL-1RA, IL-10, and Eotaxin interact closely. Molecular docking simulation showed that most of the compounds have good binding activities with critical targets.
Conclusion:
The present study identified inflammatory cytokines with causal relationships to five ocular diseases, revealing potential compounds for treating these diseases, providing a theoretical basis for further clinical practice.
Insights
This study used Mendelian randomization to link inflammatory cytokines to ocular diseases like AMD, glaucoma, DR, myopia, and cataract. Findings reveal potential therapeutic targets and natural compounds for eye conditions.
Area of Science:
- Ophthalmology and Genetics
- Immunology and Molecular Biology
Background:
- Inflammatory cytokines are implicated in various ocular diseases.
- Understanding causal links between cytokines and eye conditions is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the causal relationships between 41 inflammatory cytokines and five major ocular diseases (AMD, glaucoma, DR, myopia, cataract) using Mendelian randomization.
- To explore potential interactions between natural active ingredients and identified inflammatory cytokines via molecular docking.
Main Methods:
- A two-sample Mendelian randomization study utilizing GWAS data for ocular diseases and inflammatory cytokines.
- Employed inverse variance weighted (IVW), MR-Egger, and other methods for robust causality assessment.
- Constructed a protein-protein interaction (PPI) network and performed molecular docking to evaluate compound-target binding.
Main Results:
- Identified specific cytokines associated with ocular diseases: IL-18 and PDGF-BB protective for AMD; RANTES for glaucoma; IL-10 for DR; GROa linked to increased myopia risk.
- Eotaxin, FGF2, and GROa associated with increased cataract risk, while IL-1RA showed a protective association.
- PPI network highlighted close interactions among GROa, FGF2, IL-18, IL-1RA, IL-10, and Eotaxin; molecular docking confirmed good binding activities.
Conclusions:
- Established causal links between specific inflammatory cytokines and five common ocular diseases.
- Identified potential therapeutic targets and natural compounds for ocular disease treatment.
- Provides a foundation for future clinical research and interventions in ophthalmology.
