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Nov 12, 2024

The Complement Factor H (Y402H) risk polymorphism for age-related macular degeneration affects metabolism and response to oxidative stress in the retinal pigment epithelium

By: Peng Shang, Helena Ambrosino, Johnson Hoang, Zhaohui Geng, Xiaoyu Zhu, Shichen Shen, Mark Eminhizer, Elise Hong, Ming Zhang, Jun Qu, Jianhai Du, Sandra R. Montezuma, James R. Dutton, Deborah A. Ferrington

Age-related macular degeneration (AMD), the leading cause of central vision loss in the elderly, involves death of the retinal pigment epithelium (RPE) and light-sensing photoreceptors. This multifactorial disease includes contributions from both genetic and environmental risk factors. The current study examined the effect of the Y402H polymorphism of Complement Factor H (CFH, rs1061170) and cigarette smoke, predominant genetic and environmental risk factors associated with AMD. We used targeted and discovery-based approaches to identify genotype-dependent responses to chronic oxidative stress induced by cigarette smoke extract (CSE) in RPE differentiated from induced pluripotent stem cells (iPSC) derived from human donors harboring either the low risk (LR) or high risk (HR) CFH genotype.

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