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An iPSC patient specific model of CFH (Y402H) polymorphism displays characteristic features of AMD and indicates a beneficial role for UV light exposure

Lookup NU author(s): Dr Dean Hallam, Dr Joseph Collin, Dr Sanja Bojic, Dr Valeria Chichagova, Dr Adriana BuskinORCiD, Dr Yaobo Xu, Lucia Lafage, Dr Christian Otten, Dr George Anyfantis, Dr Carla Mellough, Dr Viktor Korolchuk, Dr Gabriele Saretzki, Professor Lyle Armstrong, Professor David SteelORCiD, Professor David KavanaghORCiD, Professor Majlinda LakoORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Hallam D, Collin j, Bojic S, Chichagova V, Buskin A, Xu Y, Lafage L, Otten EG, Anyfantis G, Mellough C, Przyboski S, Alhart S, Korolchuk V, Lotery A, Saretzki G, McKibbin M, Armstrong L, Steel D, Kavanagh D, Lako M

Publication type: Article

Publication status: Published

Journal: Stem Cells

Year: 2017

Volume: 35

Issue: 11

Pages: 2305-2320

Print publication date: 01/11/2017

Online publication date: 15/09/2017

Acceptance date: 07/09/2017

Date deposited: 08/09/2017

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: Wiley


DOI: 10.1002/stem.2708


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Funder referenceFunder name
European Research Council [614620]
IMI2 funded EbiSC project
Macular Society UK