Abstract
SignificanceGenome-wide association studies have identified two major risk loci for age-related macular degeneration (AMD) on chromosome (Chr) 1 and Chr10. Here, we use proteomics to analyze submacular stromal tissue punches from older eye donors without AMD, comparing tissue from donors who were homozygous for high-risk alleles at Chr1 or Chr10 with tissue from donors with low risk at these two loci. A common change found in Chr1/Chr10-risk eyes was increased mast cell proteases, and immunohistochemistry confirmed the presence of increased mast cell numbers. This study, therefore, provides a unifying mechanistic link between Chr1 and Chr10 risk and suggests that mast cell infiltration of the choroid and degranulation are early events in AMD pathogenesis.
| Original language | English |
|---|---|
| Article number | e2118510119 |
| Pages (from-to) | e2118510119 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 119 |
| Issue number | 20 |
| DOIs | |
| Publication status | Published - 17 May 2022 |
Bibliographical note
Funding Information:ACKNOWLEDGMENTS. This research was supported by Fight for Sight UK Grant 1517/18 and the Macular Society (United Kingdom). Development and application of the Bayesian models were funded by Medical Research Council UK Grant MR/N028457/1 (to A.W.D.). The Bioimaging Facility microscopes used in this study were purchased with grants from the Biotechnology and Biological Sciences Research Council (United Kingdom), the Wellcome Trust (United Kingdom), and the University of Manchester Strategic Fund. We thank Peter March and Roger Meadows for their help with the microscopy and Peter Walker at the University of Manchester Histology Core Facility for his support.
Publisher Copyright:
© 2022 National Academy of Sciences. All rights reserved.