Multiomics reveals fatty acid metabolism and immune remodeling in retinal artery occlusion

Retinal artery occlusion (RAO), an acute ocular ischemic stroke, is critically linked to cardiovascular and metabolic dysfunction. To elucidate the interplay between lipid metabolism and immune regulation in RAO, we performed an integrated analysis using serum metabolomics, PBMC transcriptomics, and machine learning in 66 patients with RAO and 66 cataract controls. We identified systemic disruptions in fatty acid metabolism, notably elevated levels of long-chain fatty acids (C22:5n-3, C22:2n-6, C22:1n-9), as distinguishing features of RAO. Upon stratifying patients by lipid status, C20:2n-6 emerged as the top biomarker distinguishing dyslipidemic RAO from non-dyslipidemic cases. Multiomics analysis correlated this accumulation with specific immune pathways, particularly Treg modulation. In Treg-like MT-2 cells, C20:2n-6 promoted Treg proliferation and induced the secretion of the anti-inflammatory cytokine IL-10, independent of TGF-β. These findings highlight C20:2n-6 as a candidate biomarker and implicate the C20:2n-6-Treg-IL-10 axis as a therapeutic target for restoring immune homeostasis in dyslipidemia-associated RAO.