Mapping Macrophage Diversity in Coats' Disease: A Lipid-Associated Subset in the Pathogenesis of Exudative...

Coats' disease is a retinal vasculopathy characterized by retinal telangiectasia, exudation, and retinal detachment. Lipid exudates serve as crucial biomarkers for the assessment and prediction of disease progression. However, the pathophysiological mechanisms driving exudation remain inadequately understood. This study aimed to investigate the cellular and molecular mechanisms underlying the pathogenesis of Coats' disease.

Single-cell suspensions of epiretinal membrane and vitreous samples were collected from a patient with Coats' disease, and corresponding vitreous and epiretinal membrane samples from four patients with proliferative vitreoretinopathy were used as controls. The samples were analyzed by single-cell RNA sequencing using Seurat, Slingshot, hdWGCNA, and scFEA in R/Python software.

In this study, we present the first single-cell atlas of the retinal microenvironment in Coats' disease, derived from clinical samples of epiretinal membrane and vitreous cells. Our analysis identified a predominance of macrophages, with a dominant cluster exhibiting a transcriptional profile characteristic of lipid-associated macrophages (LAMs). Single-cell trajectory and metabolic analysis revealed a gradual decrease in lipid oxidative catabolism in LAMs, with a progressive shift in biological function from phagocytosis to inflammation and extracellular matrix remodeling. Furthermore, we identified that the transition of LAMs was regulated by a gene module centered around ABCA1, a key regulator in the progression of atherosclerosis. Single-cell drug response analysis further infers that an antiatherosclerotic regimen may elicit a superior response in LAMs compared with conventional treatments.

Collectively, our characterization of LAM phenotypes may provide novel insights into the pathogenesis of Coats' disease and identify potential targets for disease-specific interventions.