Prenatally derived macrophages support choroidal health and decline in age-related macular degeneration
Year: 2025
Type: article
Abstract: Hallmark findings in age-related macular degeneration (AMD) include the accumulation of extracellular lipid and vasodegeneration of the choriocapillaris. Choroidal inflammation has long been associated with AMD, but little is known about the immune landscape of the human choroid. Using 3D multiplex immunofluorescence, single-cell RNA sequencing, and flow cytometry, we unravel the cellular composition and spatial organization of the human choroid and the immune cells within it. We identify two populations of choroidal macrophages with distinct FOLR2 expression that account for the majority of myeloid cells. FOLR2+ macrophages predominate in the nondiseased eye, express lipid-handling machinery, uptake lipoprotein particles, and contain high amounts of lipid. In AMD, FOLR2+ macrophages are decreased in number and exhibit dysfunctional lipoprotein metabolism. In mice, FOLR2+ macrophages are negative for the postnatal fate-reporter Ms4a3, and their depletion causes an accelerated AMD-like phenotype. Our results show that prenatally derived resident macrophages decline in AMD and are implicated in multiple hallmark functions known to be compromised in the disease.
DOI: 10.1084/jem.20242007
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1176171583, G2225149299, G2345600615, G2457495176, G296357158, Control of Colitogenic Th17 cells by Vitamin D Receptor Signaling, Role of choroidal macrophages in regulating lipid homeostasis and immunosuppression of the RPE/choroid, G4374442503, G4689855673, G6860983262, G9000046555, G9000068115, G9000097971, G9000119088, G9000214105, G9000309265, Center Core Grant for Vision Research, UAB Center for AIDS Research (CFAR), G946937635
OpenAlex ID: W4409734446