Exploration of potential drug targets for Glaucoma by plasma proteome screening

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.