Discovery and exploration of adaptive immune response-related drug targets in diabetic retinopathy by Mendelian randomization.

Background: Persistent diabetes raises diabetic retinopathy (DR) risk, and management is challenging. Integrating transcriptomics and MR, this study provides a current reference for the clinical treatment of DR by identifying potential drug targets in adaptive immune response-associated genes (AIR-RGs).

Methods: The GSE102485 dataset about AIR-RGs and DR was downloaded from a public database. Initially, the MR and Steiger test identified AIR-related candidate genes with causal associations to DR. Bayesian co-localization analysis pinpointed DR drug targets, followed by phenotype scanning for side effects. Functional enrichment and immune infiltration analyses elucidated target mechanisms in DR.

Results: Identified 27 AIR-RGs associated with DR, with TRAV23DV6 (OR = 1.367, 95 % CI = 1.005-1.859, p = 0.0046) as a risk factor. Co-localization analysis confirmed TRAV23DV6's potential as a DR drug target. Phenotype scanning linked TRAV23DV6 to hepatocellular carcinoma, thromboembolism, and pyelonephritis, indicating potential side effects. TRAV23DV6 engages in adaptive immunity, autophagy, and antigen binding. DR involves infiltration of 22 immune cell types and activation of 16 immune functions related to TCR, BCR pathways, and TNF family. Correlation analysis shows high TRAV23DV6 expression, immune cell infiltration, and function activation may exacerbate DR.

Conclusion: TRAV23DV6 has been identified as a potential drug target for DR, offering a new perspective for the treatment of this condition.