Investigating the relationship between blood metabolites and diabetic retinopathy using two-sample mendelian randomization and in vivo validation.

We addressed fundamental questions about the influence of metabolites on the development of Diabetic retinopathy (DR), and explored the related pathological mechanism. Genome-wide association study (GWAS) database data for metabolites and DR were used to perform Mendelian randomization (MR) studies. The inverse variance weighting (IVW) was chosen as the primary analysis method. Sensitivity analysis was conducted using MR-PRESSO, leave-one-out and Cochran's Q test. Confounding factors were eliminated to ensure robustness. We also conducted metabolic pathway analysis. In vivo experimental validation was conducted using Sprague Dawley rats. The serum metabolites of the DR group rats and normal group rats were examined to evaluate the MR results. The screen identified eighteen metabolites associated with DR risk, twelve of which were known components. Seven metabolites were positively correlated with DR risk, while five could reduce it. Eight metabolites associated with proliferative DR (PDR) risk were identified, four of which are known components. Three of these were positively associated with PDR risk and one metabolite reduced PDR risk. Additionally, two possible metabolic pathways involved in the biological mechanism of DR were identified. The ELISA results showed that the serum levels of isoleucine and 4-HPA were significantly increased in DR rats, while the level of inosine was decreased. This study offers novel insights into the biological mechanisms underlying DR. Metabolites that are causally linked to DR may serve as promising biomarkers and therapeutic targets.

Rheumatoid arthritis and diabetic retinopathy: A two-sample Mendelian randomization study.

Diabetic retinopathy (DR) is a common and highly blinding disease. Many clinical studies have shown a causal relationship between Rheumatoid arthritis (RA) and DR, but the results are contradictory. In addition, some clinical results and pathological inferences have certain paradoxes, and the influence of RA on the pathogenesis and development of DR Is unclear. Our research assessed the causal association between RA and the development of DR using a 2-sample Mendelian randomization method. Single nucleotide polymorphisms (SNPs) relevant to the study were extracted and filtered from genome-wide association study (GWAS) data. A DR GWAS with a sample size of 190,594 and an RA GWAS with a sample size of 58,284 were obtained. Inverse variance weighted (IVW) method was used to analyze the results, and Mendelian randomization (MR)-Egger regression method and weighted median method were used to evaluate the robustness. Sensitivity analysis was performed using pleiotropy test, heterogeneity test, leave-one-out test to ensure that the results were unbiased. Confounding factors were eliminated to ensure robustness. A total of 83 related SNPs were screened. IVW method showed a positive correlation between RA and the increased relative risk of diabetic retinopathy (OR = 1.06, 95%CI: 1.04-1.23). The same trend was shown by MR-Egger regression method and weighted median method. Sensitivity analysis showed that there was no heterogeneity in SNPs, and the results were less likely to be affected by potential bias. After removing SNPs linked to confounders, the MR results remained significant and stable in direction. There is a positive causal association between rheumatoid arthritis and diabetic retinopathy. It is important to strengthen retina-related screening and prevention in diabetic patients with RA to reduce the risk of DR In RA patients.