Frontiers in Immunology (Jun 2022)
As in Real Estate, Location Matters: Cellular Expression of Complement Varies Between Macular and Peripheral Regions of the Retina and Supporting Tissues
- Randy Zauhar,
- Josef Biber,
- Yassin Jabri,
- Mijin Kim,
- Jian Hu,
- Lew Kaplan,
- Anna M. Pfaller,
- Nicole Schäfer,
- Nicole Schäfer,
- Volker Enzmann,
- Volker Enzmann,
- Ursula Schlötzer-Schrehardt,
- Tobias Straub,
- Stefanie M. Hauck,
- Paul D. Gamlin,
- Michael B. McFerrin,
- Jeffrey Messinger,
- Christianne E. Strang,
- Christine A. Curcio,
- Nicholas Dana,
- Diana Pauly,
- Diana Pauly,
- Antje Grosche,
- Mingyao Li,
- Dwight Stambolian
Affiliations
- Randy Zauhar
- Department of Chemistry and Biochemistry, The University of the Sciences in Philadelphia, Philadelphia, PA, United States
- Josef Biber
- Department of Physiological Genomics, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany
- Yassin Jabri
- Department of Ophthalmology, University Hospital Regensburg, Regensburg, Germany
- Mijin Kim
- Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
- Jian Hu
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
- Lew Kaplan
- Department of Physiological Genomics, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany
- Anna M. Pfaller
- Department of Physiological Genomics, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany
- Nicole Schäfer
- Department of Ophthalmology, University Hospital Regensburg, Regensburg, Germany
- Nicole Schäfer
- Department of Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology (ZMB), University of Regensburg, Regensburg, Germany
- Volker Enzmann
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Volker Enzmann
- Department of BioMedical Research, University of Bern, Bern, Switzerland
- Ursula Schlötzer-Schrehardt
- Department of Ophthalmology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Tobias Straub
- 0Bioinformatics Unit, Biomedical Center, Ludwig-Maximilians-University Munich, Planegg-Martinsried, Germany
- Stefanie M. Hauck
- 1Metabolomics and Proteomics Core and Research Unit Protein Science, Helmholtz-Zentrum München, Neuherberg, Germany
- Paul D. Gamlin
- 2Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL, United States
- Michael B. McFerrin
- 3Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, United States
- Jeffrey Messinger
- 2Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL, United States
- Christianne E. Strang
- 3Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, United States
- Christine A. Curcio
- 2Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL, United States
- Nicholas Dana
- Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
- Diana Pauly
- Department of Ophthalmology, University Hospital Regensburg, Regensburg, Germany
- Diana Pauly
- 4Experimental Ophthalmology, University of Marburg, Marburg, Germany
- Antje Grosche
- Department of Physiological Genomics, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany
- Mingyao Li
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
- Dwight Stambolian
- Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
- DOI
- https://doi.org/10.3389/fimmu.2022.895519
- Journal volume & issue
-
Vol. 13
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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