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Zauhar, R.* ; Biber, J.* ; Jabri, Y.* ; Kim, M.* ; Hu, J.* ; Kaplan, L.* ; Pfaller, A.M.* ; Schaefer, N.* ; Enzmann, V.* ; Schloetzer-Schrehardt, U.* ; Straub, T.* ; Hauck, S.M. ; Gamlin, P.D.* ; McFerrin, M.B.* ; Messinger, J.* ; Strang, C.E.* ; Curcio, C.A.* ; Dana, N.* ; Pauly, D.* ; Grosche, A.* ; Li, M.* ; Stambolian, D.*

As in real estate, location matters: Cellular expression of complement varies between macular and peripheral regions of the retina and supporting Tissues.

Front. Immunol. 13:895519 (2022)

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The cellular events that dictate the initiation of the complement pathway in ocular degeneration, such as age-related macular degeneration (AMD), is poorly understood. Using gene expression analysis (single cell and bulk), mass spectrometry, and immunohistochemistry, we dissected the role of multiple retinal and choroidal cell types in determining the complement homeostasis. Our scRNA-seq data show that the cellular response to early AMD is more robust in the choroid, particularly in fibroblasts, pericytes and endothelial cells. In late AMD, complement changes were more prominent in the retina especially with the expression of the classical pathway initiators. Notably, we found a spatial preference for these differences. Overall, this study provides insights into the heterogeneity of cellular responses for complement expression and the cooperation of neighboring cells to complete the pathway in healthy and AMD eyes. Further, our findings provide new cellular targets for therapies directed at complement.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Single Cell ; Complement ; Age-related Macular Degeneration ; Retina ; Rpe ; Choroid

ISSN (print) / ISBN 1664-3224

e-ISSN 1664-3224

Journal Frontiers in Immunology

Quellenangaben Volume: 13, Article Number: 895519

Publisher Frontiers

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CF Metabolomics & Proteomics (CF-MPC)

Grants NEI NIH HHS