Dr Chloe Stanton

Late-onset retinal degeneration (L-ORD) is a rare inherited eye disease that causes progressive vision loss later in life. It is passed down in families and usually leads to severe sight loss. While people with L-ORD can receive support, such as genetic counselling and visual aids, there are currently no treatments available. This condition has a major impact on those affected and their families. A key barrier to developing treatments is that we still do not fully understand what causes the disease at the cellular level.

Previous research has shown that changes (mutations) in a gene called C1QTNF5 cause L-ORD. This gene produces a protein found in the retinal pigment epithelium (RPE), cells that are vital for healthy vision. We want to better understand how these gene changes harm the RPE and explore potential ways to fix or reduce this damage.

Research interests

The leading cause of sight loss in the developed world is age-related macular degeneration (AMD; 6-9% legal blindness), a common disease with genetic and environmental risk factors. AMD causes sight loss in 700,000 people in the UK. 200 new cases are diagnosed every day. By 2040, 288 million people worldwide will experience sight loss from AMD. Inherited retinal diseases (IRDs) are rare conditions that cumulatively affect 1 in 2000 people. Some resemble AMD, but in Late-onset retinal degeneration (L-ORD) and Doyne honeycomb dystrophy (DHD), visual impairment occurs earlier, progresses more rapidly and is more severe. These IRDs and AMD arise from progressive retinal pigment epithelial (RPE) cell dysfunction, disturbed retinal homeostasis and photoreceptor death.

Our overarching research aims are to:

• identify genetic causes of inherited sight loss
• understand molecular pathomechanisms
• identify targets and test novel strategies to protect retinal cells to preserve vision

To achieve these aims we utilise a range of models, including induced pluripotent stem cells (iPSC), that can be differentiated into many different types of cells including RPE, photoreceptors and retinal organoids. These are studied using advanced genomic, transcriptomic and proteomic approaches to build a picture of what goes wrong in disease and how this can be stopped.

Research theme

Translational medicine

Key projects

Late Onset Retinal Macular Degeneration (L-ORD) research

International Age-related Macular Degeneration (AMD) Genomic Consortium

Selected recent publications

Gorman BR, Voloudakis G, Igo RP Jr, et al. Genome-wide association analyses identify distinct genetic architectures for age-related macular degeneration across ancestries. Nat Genet. 2024;56(12):2659-2671. doi:10.1038/s41588-024-01764-0

Li RTH, Roman AJ, Sumaroka A, et al. Treatment Strategy With Gene Editing for Late-Onset Retinal Degeneration Caused by a Founder Variant in C1QTNF5. Invest Ophthalmol Vis Sci. 2023;64(15):33. doi:10.1167/iovs.64.15.33

Young SL*, Stanton CM*, Livesey BJ, Marsh JA, Cackett PD. Novel biallelic USH2A variants in a patient with usher syndrome type IIA- a case report. BMC Ophthalmol. 2022;22(1):140. Published 2022 Mar 26. doi:10.1186/s12886-022-02353-7

Stanton CM*, Findlay AS*, Drake C, et al. A mouse model of brittle cornea syndrome caused by mutation in Zfp469. Dis Model Mech. 2021;14(9):dmm049175. doi:10.1242/dmm.049175

Klarić L*, Tsepilov YA*, Stanton CM*, et al. Glycosylation of immunoglobulin G is regulated by a large network of genes pleiotropic with inflammatory diseases. Sci Adv. 2020;6(8):eaax0301. Published 2020 Feb 19. doi:10.1126/sciadv.aax0301

Chekuri A, Zientara-Rytter K, Soto-Hermida A, et al. Late-onset retinal degeneration pathology due to mutations in CTRP5 is mediated through HTRA1. Aging Cell. 2019;18(6):e13011. doi:10.1111/acel.13011

Borooah S, Stanton CM, Marsh J, et al. Whole genome sequencing reveals novel mutations causing autosomal dominant inherited macular degeneration. Ophthalmic Genet. 2018;39(6):763-770. doi:10.1080/13816810.2018.1546406

Stanton CM, Borooah S, Drake C, et al. Novel pathogenic mutations in C1QTNF5 support a dominant negative disease mechanism in late-onset retinal degeneration. Sci Rep. 2017;7(1):12147. Published 2017 Sep 22. doi:10.1038/s41598-017-11898-3

Fritsche LG, Igl W, Bailey JN, et al. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet. 2016;48(2):134-143. doi:10.1038/ng.3448

Ansari M, McKeigue PM, Skerka C, et al. Genetic influences on plasma CFH and CFHR1 concentrations and their role in susceptibility to age-related macular degeneration. Hum Mol Genet. 2013;22(23):4857-4869. doi:10.1093/hmg/ddt336

*joint first author

Group members

Petra Lavay, PhD student (co-supervised with Dr. Mihaela Crisan)

Muye Liu, PhD student (co-supervised with Prof. Mathew Horrocks)

Collaborators

Internal collaborators

Dr Mihaela Crisan

Dr Beth Mills

Professor Caroline Hayward

Dr Veronique Vitart

Professor Baljean Dhillon

Dr Roly Megaw

Professor Joseph A. Marsh

Dr Ewen Calder

Professor Mathew Horrocks

Professor Paul Barlow

Professor Jim Wilson

External collaborators

Professor Robin Ali

Mr Andrew Browning

Dr Shyamanga Borooah

Professor Amanda Carr

Dr Ines Cebola

Professor Artur V. Cideciyan

Professor Mariya Moosajee

Professor Marius Ueffing

International AMD Genomics Consortium (IAMDGC)

Funders

Fight for Sight