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Updated: Jun 11, 2025
Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
Exploration of potential drug targets for Glaucoma by plasma proteome screening
Zhiqi Wang1, Huanyu Zhou2, Fei Wang1
1Jiangnan University Affiliated Wuxi Fifth People's Hospital, Wuxi 214000, Jiangsu, China.
Background:
Glaucoma is the leading cause of irreversible blindness. However, the current available treatment methods are still unsatisfactory. Therefore, the exploration of new drug targets for the treatment of glaucoma is of paramount importance.
Methods:
We conducted two-sample Mendelian randomization (MR) using plasma protein quantitative trait loci (pQTL) data from two datasets (n = 734, n = 4907) and their instrumental variables to investigate the causal relationship between plasma proteins and glaucoma. The analysis was validated by replacing the exposure and outcome cohorts. Additionally, we utilized protein-protein interaction networks to assess the associations between these potential drug targets and existing drug targets.
Results:
Through two-sample Mendelian randomization analysis, we identified causal relationships between Glaucoma and the following proteins: AZU1, OBP2B, ENPP5, INPP5B, KREMEN1, LYPLAL1, and PTPRJ. External validation confirmed the protective effect of LYPLAL1 on Glaucoma, while ENPP5, KREMEN1, and PTPRJ increased the risk of Glaucoma. Reverse MR and Steiger filtering did not indicate any reverse causal associations of the aforementioned proteins with Glaucoma.
Conclusion:
Our study demonstrates a causal impact of ENPP5, KREMEN1, PTPRJ, and LYPLAL1 on the risk of Glaucoma. These findings suggest that these four proteins may serve as promising drug targets for Glaucoma treatment.
Significance:
Currently, the pharmacological treatment of glaucoma primarily focuses on lowering intraocular pressure, which has its limitations. Targeted therapy is a personalized treatment approach that aims to inhibit or block the development and progression of diseases such as cancer and inflammation by selectively acting on specific biomolecules or signaling pathways. Our research employs a two-sample Mendelian randomization (MR) method, integrating a large amount of GWAS and pQTL data to perform MR analysis. This has enabled us to explore several plasma proteins as potential drug targets for glaucoma, providing direction and a research foundation for future investigations into glaucoma drug targets.
