Ongoing controversies and recent insights of the ARMS2-HTRA1 locus in age-related macular degeneration

doi:10.1016/j.exer.2021.108605

Review

. 2021 Sep:210:108605.

doi: 10.1016/j.exer.2021.108605. Epub 2021 Apr 28.

Ongoing controversies and recent insights of the ARMS2-HTRA1 locus in age-related macular degeneration

Adam May¹, Fei Su², Brian Dinh³, Rachael Ehlen⁴, Christina Tran⁵, Harini Adivikolanu⁶, Peter X Shaw⁷

Affiliations

¹ Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: a5may@ucsd.edu.
² Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: sophiasucn@gmail.com.
³ Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: btdinh@ucsd.edu.
⁴ Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: rachael.ehlen@gmail.com.
⁵ Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: cdtran@ucsd.edu.
⁶ Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: hadiviko@ucsd.edu.
⁷ Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: pshaw@ucsd.edu.

PMID: 33930395
DOI: 10.1016/j.exer.2021.108605

Review

Ongoing controversies and recent insights of the ARMS2-HTRA1 locus in age-related macular degeneration

Adam May et al. Exp Eye Res. 2021 Sep.

. 2021 Sep:210:108605.

doi: 10.1016/j.exer.2021.108605. Epub 2021 Apr 28.

Authors

Adam May¹, Fei Su², Brian Dinh³, Rachael Ehlen⁴, Christina Tran⁵, Harini Adivikolanu⁶, Peter X Shaw⁷

Affiliations

¹ Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: a5may@ucsd.edu.
² Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: sophiasucn@gmail.com.
³ Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: btdinh@ucsd.edu.
⁴ Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: rachael.ehlen@gmail.com.
⁵ Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: cdtran@ucsd.edu.
⁶ Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: hadiviko@ucsd.edu.
⁷ Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA; Altman Clinical and Translational Research Institute, University of California, San Diego, 9452 Medical Center Drive, La Jolla, CA 92093-0990, USA. Electronic address: pshaw@ucsd.edu.

PMID: 33930395
DOI: 10.1016/j.exer.2021.108605

Abstract

Age-related macular degeneration (AMD) is the most common cause of central vision loss among elderly populations in industrialized countries. Genome-wide association studies have consistently associated two genomic loci with progression to late-stage AMD: the complement factor H (CFH) locus on chromosome 1q31 and the age-related maculopathy susceptibility 2-HtrA serine peptidase 1 (ARMS2-HTRA1) locus on chromosome 10q26. While the CFH risk variant has been shown to alter complement activity, the ARMS2-HTRA1 risk haplotype remains enigmatic due to high linkage disequilibrium and inconsistent functional findings spanning two genes that are plausibly causative for AMD risk. In this review, we detail the genetic and functional evidence used to support either ARMS2 or HTRA1 as the causal gene for AMD risk, emphasizing both the historical development and the current understanding of the ARMS2-HTRA1 locus in AMD pathogenesis. We conclude by summarizing the evidence in favor of HTRA1 and present our hypothesis whereby HTRA1-derived ECM fragments mediate AMD pathogenesis.

Keywords: ARMS2-HTRA1 gene locus; Age-related macular degeneration; Complement system; Extracellular matrix; Linkage disequilibrium; TGF-Beta signaling.

PubMed Disclaimer

Cited by

CRISPR editing demonstrates rs10490924 raised oxidative stress in iPSC-derived retinal cells from patients with ARMS2/HTRA1-related AMD.
Chang YJ, Jenny LA, Li YS, Cui X, Kong Y, Li Y, Sparrow JR, Tsang SH. Chang YJ, et al. Proc Natl Acad Sci U S A. 2023 May 9;120(19):e2215005120. doi: 10.1073/pnas.2215005120. Epub 2023 May 1. Proc Natl Acad Sci U S A. 2023. PMID: 37126685 Free PMC article.
Nanotechnology Lighting the Way for Gene Therapy in Ophthalmopathy: From Opportunities toward Applications.
Ren W, Duan S, Dai C, Xie C, Jiang L, Shi Y. Ren W, et al. Molecules. 2023 Apr 15;28(8):3500. doi: 10.3390/molecules28083500. Molecules. 2023. PMID: 37110734 Free PMC article. Review.
Rare complement factor I variants associated with reduced macular thickness and age-related macular degeneration in the UK Biobank.
Tzoumas N, Kavanagh D, Cordell HJ, Lotery AJ, Patel PJ, Steel DH. Tzoumas N, et al. Hum Mol Genet. 2022 Aug 23;31(16):2678-2692. doi: 10.1093/hmg/ddac060. Hum Mol Genet. 2022. PMID: 35285476 Free PMC article.
Transcriptomics Analysis of Lens from Patients with Posterior Subcapsular Congenital Cataract.
Lin X, Li H, Yang T, Liu X, Fan F, Zhou X, Luo Y. Lin X, et al. Genes (Basel). 2021 Nov 27;12(12):1904. doi: 10.3390/genes12121904. Genes (Basel). 2021. PMID: 34946854 Free PMC article.

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

Grants and funding

P30 EY022589/EY/NEI NIH HHS/United States

LinkOut - more resources

Full Text Sources
- Elsevier Science
- Ovid Technologies, Inc.
Other Literature Sources
- scite Smart Citations
Medical
- Genetic Alliance
- MedlinePlus Health Information
Molecular Biology Databases
- GlyGen glycoinformatics resource
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Ongoing controversies and recent insights of the ARMS2-HTRA1 locus in age-related macular degeneration

Affiliations

Ongoing controversies and recent insights of the ARMS2-HTRA1 locus in age-related macular degeneration

Authors

Affiliations

Abstract

Similar articles

Cited by

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Miscellaneous

Abstract

Similar articles

Cited by

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Miscellaneous