Bringing the age-related macular degeneration high-risk allele age-related maculopathy susceptibility 2 into focus with stem cell technology.

Abstract

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.

• Authors: Shuo Sun, ZhiQing Li, Patrick Glencer, BinCui Cai, XiaoMin Zhang, Jin Yang, XiaoRong Li
• Journal: Stem cell research & therapy (Stem Cell Res Ther) Vol. 8 Issue 1 Pg. 135 (06 06 2017) ISSN: 1757-6512 [Electronic] England
• PMID: 28583181 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't)

Chemical References

• ARMS2 protein, human
• Proteins
• High-Temperature Requirement A Serine Peptidase 1
• HtrA1 protein, human

Topics

• Alleles
• Cell Differentiation (genetics)
• Genotype
• High-Temperature Requirement A Serine Peptidase 1 (genetics)
• Humans
• Induced Pluripotent Stem Cells (metabolism, transplantation)
• Macular Degeneration (genetics, pathology, therapy)
• Proteins (genetics)
• Retinal Degeneration (genetics, pathology, therapy)
• Retinal Pigment Epithelium (metabolism, pathology)
• Risk Factors
• Stem Cell Transplantation