Role of ceramide-regulated metabolic intermediates in retinal vein occlusion
10.3980/j.issn.1672-5123.2025.9.17
- VernacularTitle:神经酰胺调控中间代谢产物对视网膜静脉阻塞的作用
- Author:
Biao YANG
1
;
Chuanqi XIE
1
Author Information
1. Department of Ophthalmology, the First People's Hospital of Shangqiu, Shangqiu 476100, Henan Province, China
- Publication Type:Journal Article
- Keywords:
ceramide;
Mendelian randomization;
retinal vein occlusion;
metabolites;
mediation analysis
- From:
International Eye Science
2025;25(9):1484-1490
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the causal effects of ceramides on retinal vein occlusion(RVO)and elucidate their potential mediating mechanisms using Mendelian randomization(MR)analysis.METHODS: Genome-wide association study(GWAS)data for four ceramide species were utilized as exposures, and RVO GWAS data from the FinnGen database as the outcome. Additionally, GWAS data for 1 400 intermediate metabolites were analyzed to identify potential mediators in the ceramide-RVO pathway.RESULTS: Two ceramide species exhibited significant causal associations with RVO: ceramide(d40:1)[IVW OR(95% CI): 0.750(0.604-0.930), P<0.05] and ceramide(d42:2)[IVW OR(95% CI): 0.771(0.632-0.941), P<0.05], suggesting protective effects. Mediation analysis revealed that ceramide(d40:1)influenced RVO risk through metabolites including 3-methylxanthine, branched/straight-chain/cyclopropyl 10:1 fatty acids, glutamine, and hydroxypalmitoyl sphingomyelin. Similarly, ceramide(d42:2)acted via N-methylhydroxyproline, the same fatty acid group, N1-methyladenosine, and the leucine-to-N-palmitoyl-sarcosinate ratio.CONCLUSION: Ceramides(d40:1)and(d42:2)confer protection against RVO, partially mediated by specific metabolic pathways.
