As in Real Estate, Location Matters: Cellular Expression of Complement Varies Between Macular and Peripheral Regions of the Retina and Supporting Tissues

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Jul 5

PMID 35784369

Authors

Randy Zauhar

Josef Biber

Yassin Jabri

Mijin Kim

Jian Hu

Lew Kaplan

Anna M Pfaller

Nicole Schafer

Volker Enzmann

Ursula Schlotzer-Schrehardt

Tobias Straub

Stefanie M Hauck

Paul D Gamlin

Michael B McFerrin

Jeffrey Messinger

Christianne E Strang

Christine A Curcio

Nicholas Dana

Diana Pauly

Antje Grosche

Mingyao Li

Dwight Stambolian

Affiliations

Soon will be listed here.

Abstract

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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