Natural active ingredients targeted inflammatory cytokines and major blinding eye diseases: a two-sample Mendelian randomization and molecular docking analysis.

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, 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.