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Collagen-producing eye cell atlas reveals distinct fibroblast fates in early injury vs. fibrotic subretinal disease
Journal article   Open access   Peer reviewed

Collagen-producing eye cell atlas reveals distinct fibroblast fates in early injury vs. fibrotic subretinal disease

Ema Ozaki, Said Aktas, Kelly Mulfaul, Kiva Brennan, Christophe Roubeix, Sarah Palko, Katie Robb, Tai-Hsien Ou Yang, Marie-Claire Schanne-Klein, Anna Toidze, …
Proceedings of the National Academy of Sciences - PNAS, Vol.123(26), e2519056123
06/30/2026
DOI: 10.1073/pnas.2519056123
PMID: 42361041
url
https://doi.org/10.1073/pnas.2519056123View
Published (Version of record) Open Access

Abstract

Fibrosis is the end-stage of a maladaptive process that occurs when the body's normal wound-healing strategy becomes dysregulated. Subretinal fibrosis is the end stage of neovascular age-related macular degeneration (nAMD), the most common cause of central vision loss in people over the age of 50. The cellular sources of excess extracellular matrix (ECM) contributing to subretinal fibrosis are unknown, as is the heterogeneity of cells involved in the fibrotic process. Here we identify cells contributing to subretinal fibrosis by using -YFP reporter mice to noninvasively image collagen production in real-time in vivo in two disease models, 1) a resolving retinal injury model and 2) a fibrotic model of subretinal disease. We create a collagen-producing eye cell atlas for subretinal injury and demonstrate subretinal fibroblast heterogeneity in healthy, resolving, and fibrotic tissue. We identify distinct molecular characteristics of general repair/resolving fibroblast populations versus pathogenic pro-fibrotic collagen-producing fibroblasts. Integration of this collagen-producing eye cell atlas with a published collagen-producing lung cell atlas shows conserved pro-fibrotic fibroblasts in both organs, yet also uncovers tissue-specific fibroblast populations unique to subretinal fibrosis. A fibroblast population significantly expands in subretinal fibrosis that expresses the highest levels of collagens and distinctively expresses ECM components , and . Immunolabeling of mouse and human-donor eye tissue support the fibroblastic expression and perivascular location of periostin as clearly distinguishing between bona fide fibrosis and early disease in nAMD. Our collagen-producing eye cell atlas is a valuable resource for studying distinct fibroblast subsets in homeostasis, early injury, and fibrosis.
 Animals Cell Adhesion Molecules Collagen - metabolism Collagen Type I - genetics Collagen Type I - metabolism Disease Models, Animal Extracellular Matrix - metabolism Fibroblasts - metabolism Fibroblasts - pathology Fibrosis - metabolism Humans Macular Degeneration - metabolism Macular Degeneration - pathology Mice Periostin Retina - metabolism Retina - pathology

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