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Journal Article
Research Support, Non-U.S. Gov't
Review
Bringing the age-related macular degeneration high-risk allele age-related maculopathy susceptibility 2 into focus with stem cell technology.
Stem Cell Research & Therapy 2017 June 7
Age-related macular degeneration (AMD) is a major cause of blindness in older adults in developed countries. It is a multifactorial disease triggered by both environmental and genetic factors. High-temperature requirement A serine peptidase 1 (HTRA1) and age-related maculopathy susceptibility 2 (ARMS2) are two genes that are strongly associated with AMD. Because ARMS2 is an evolutionarily recent primate-specific gene and because the ARMS2/HTRA1 genes are positioned at a locus on chromosome 10q26 in a region with strong linkage disequilibrium, it is difficult to distinguish the functions of the individual genes. Therefore, it is necessary to bring these genes into focus. Patient-specific induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) provides direct access to a patient's genetics and allows for the possibility of identifying the initiating events of RPE-associated degenerative diseases. In this paper, a review of recent epidemiological studies of AMD is offered. An argument for a definite correlation between the ARMS2 gene and AMD is presented. A summary of the use of ARMS2 genotyping for medical treatment is provided. Several ARMS2-related genetic models based on such stem cells as iPSCs are introduced. The possibility of applying gene-editing techniques and stem-cell techniques to better explore the mechanisms of the ARMS2 high-risk allele, which will lead to important guidance for treatment, is also discussed.
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