Dean Hallam
An iPSC Patient Specific Model of CFH (Y402H) Polymorphism Displays Characteristic Features of AMD and Indicates a Beneficial Role for UV Light Exposure
Hallam, Dean; Collin, Joseph; Bojic, Sanja; Chichagova, Valeria; Buskin, Adriana; Xu, Yaobo; Lafage, Lucia; Otten, Elsje. G.; Anyfantis, George; Mellough, Carla; Przyborski, Stefan; Alharthi, Sameer; Korolchuk, Viktor; Lotery, Andrew; Saretzki, Gabriele; McKibbin, Martin; Armstrong, Lyle; Steel, David; Kavanagh, David; Lako, Majlinda
Authors
Joseph Collin
Sanja Bojic
Valeria Chichagova
Adriana Buskin
Yaobo Xu
Lucia Lafage
Elsje. G. Otten
George Anyfantis
Carla Mellough
Professor Stefan Przyborski stefan.przyborski@durham.ac.uk
Deputy Provost
Sameer Alharthi
Viktor Korolchuk
Andrew Lotery
Gabriele Saretzki
Martin McKibbin
Lyle Armstrong
David Steel
David Kavanagh
Majlinda Lako
Abstract
Age related macular degeneration (AMD) is the most common cause of blindness, accounting for 8.7% of all blindness globally. Vision loss is caused ultimately by apoptosis of the retinal pigment epithelium (RPE) and overlying photoreceptors. Treatments are evolving for the wet form of the disease, however these do not exist for the dry form. Complement factor H (CFH) polymorphism in exon 9 (Y402H) has shown a strong association with susceptibility to AMD resulting in complement activation, recruitment of phagocytes, retinal pigment epithelium (RPE) damage and visual decline. We have derived and characterised induced pluripotent stem cell (iPSCs) lines from two patients without AMD and low risk genotype and two patients with advanced AMD and high risk genotype and generated RPE cells that show local secretion of several proteins involved in the complement pathway including factor H (FH), factor I (FI) and factor H like 1 (FHL-1). The iPSC RPE cells derived from high risk patients mimic several key features of AMD including increased inflammation and cellular stress, accumulation of lipid droplets, impaired autophagy and deposition of “drüsen” like deposits. The low and high risk RPE cells respond differently to intermittent exposure to UV light which leads to an improvement in cellular and functional phenotype only in the high risk AMD-RPE cells. Taken together our data indicate that the patient specific iPSC model provides a robust platform for understanding the role of complement activation in AMD, evaluating new therapies based on complement modulation and drug testing.
Citation
Hallam, D., Collin, J., Bojic, S., Chichagova, V., Buskin, A., Xu, Y., …Lako, M. (2017). An iPSC Patient Specific Model of CFH (Y402H) Polymorphism Displays Characteristic Features of AMD and Indicates a Beneficial Role for UV Light Exposure. Stem Cells, 35(11), 2305-2320. https://doi.org/10.1002/stem.2708
Journal Article Type | Article |
---|---|
Acceptance Date | Sep 7, 2017 |
Online Publication Date | Oct 9, 2017 |
Publication Date | Oct 9, 2017 |
Deposit Date | Oct 5, 2017 |
Publicly Available Date | Oct 9, 2017 |
Journal | STEM CELLS |
Print ISSN | 1066-5099 |
Electronic ISSN | 1549-4918 |
Publisher | Oxford University Press |
Peer Reviewed | Peer Reviewed |
Volume | 35 |
Issue | 11 |
Pages | 2305-2320 |
DOI | https://doi.org/10.1002/stem.2708 |
Public URL | https://durham-repository.worktribe.com/output/1374872 |
Files
Published Journal Article
(1.3 Mb)
PDF
Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
Accepted Journal Article
(7.9 Mb)
PDF
Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
Published Journal Article (Advance online version)
(1.3 Mb)
PDF
Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
Copyright Statement
Advance online version © 2017 The Authors STEM CELLS published by
Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
You might also like
Downloadable Citations
About Durham Research Online (DRO)
Administrator e-mail: dro.admin@durham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2025
Advanced Search