As in Real Estate, Location Matters: Cellular Expression of Complement Varies Between Macular and Peripheral Regions of the Retina and Supporting Tissues.
RPE/choroid
age-related macular degeneration
complement
retina
single cell
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
13
03
2022
accepted:
11
05
2022
entrez:
5
7
2022
pubmed:
6
7
2022
medline:
7
7
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35784369
doi: 10.3389/fimmu.2022.895519
pmc: PMC9240314
doi:
Substances chimiques
Complement System Proteins
9007-36-7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
895519Subventions
Organisme : NEI NIH HHS
ID : P30 EY003039
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY031209
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY030192
Pays : United States
Organisme : NEI NIH HHS
ID : R21 EY031877
Pays : United States
Informations de copyright
Copyright © 2022 Zauhar, Biber, Jabri, Kim, Hu, Kaplan, Pfaller, Schäfer, Enzmann, Schlötzer-Schrehardt, Straub, Hauck, Gamlin, McFerrin, Messinger, Strang, Curcio, Dana, Pauly, Grosche, Li and Stambolian.
Déclaration de conflit d'intérêts
CC is a consultant for Apellis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.
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