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Aging and disease    2020, Vol. 11 Issue (5) : 1219-1234     DOI: 10.14336/AD.2019.1126
Review Article |
An Updated Review of the Epigenetic Mechanism Underlying the Pathogenesis of Age-related Macular Degeneration
Li Xiaohua1,2,3,4, He Shikun1,2,3,4,5,6,*, Zhao Mingwei6,*
1Henan Provincial People’s Hospital, Zhengzhou, China.
2Henan Eye Hospital, Henan Eye Institute, Henan Key Laboratory of Ophthalmology and Visual Science, Zhengzhou, China.
3People’s Hospital of Zhengzhou University, Zhengzhou, China.
4People’s Hospital of Henan University, Zhengzhou, China.
5Departments of Pathology and Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
6Ophthalmology Optometry Centre, Peking University People’s Hospital, Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China.
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Epigenetics has been recognized to play an important role in physiological and pathological processes of the human body. Accumulating evidence has indicated that epigenetic mechanisms contribute to the pathogenesis of age-related macular degeneration (AMD). Although the susceptibility related to genetic variants has been revealed by genome-wide association studies, those genetic variants may predict AMD risk only in certain human populations. Other mechanisms, particularly those involving epigenetic factors, may play an important role in the pathogenesis of AMD. Therefore, we briefly summarize the most recent reports related to such epigenetic mechanisms, including DNA methylation, histone modification, and non-coding RNA, and the interplay of genetic and epigenetic factors in the pathogenesis of AMD.

Keywords age-related macular degeneration      epigenetics      single nucleotide polymorphisms     
Corresponding Authors: He Shikun,Zhao Mingwei   
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These authors contributed equally to this work.

Just Accepted Date: 05 December 2019   Issue Date: 22 September 2020
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Li Xiaohua
He Shikun
Zhao Mingwei
Cite this article:   
Li Xiaohua,He Shikun,Zhao Mingwei. An Updated Review of the Epigenetic Mechanism Underlying the Pathogenesis of Age-related Macular Degeneration[J]. Aging and disease, 2020, 11(5): 1219-1234.
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Figure 1.  Inhibition of CNV by TSA may involve multiple mechanisms: (1) Suppression of HIF1α and inflammatory cytokines as well as VEGF expression; (2) Inhibition of the phosphorylation of VEGF receptor 2 induced by VEGF; (3) Inhibition of activation of MAPK; (4) Upregulation of the expression of the anti-angiogenesis factor PEDF. CNV, choroidal neovascularization; TSA, trichostatin A.
Figure 2.  Function of SIRT1. Biological functions of Sirt1 are broad, ranging from aging, anti-oxidative protection of cells, inhibition of inflammation, angiogenesis, and fibrosis, and tumorigenesis suppression.
Figure 3.  Resveratrol inhibits experimental CNV.Resveratrol inhibits VEGF receptor 2 phosphorylation (P-VEGF-R2) in mice with a choroidal neovascular (CNV) lesion induced by laser, as showed by immunofluorescence. Green indicates positive staining of P-VEGF-R2 and red is propidium iodide (PI) staining. Yellow represents double labeling. the P-VEGF-R2 staining is considerably reduced in mice with a CNV lesion after resveratrol application (square). Original magnification ×400.
Figure 4.  Relevance of RNA methylation to cellular processes. RNA methylation may impact various cellular processes, including cell differentiation, proliferation, migration metabolism, and regulation of inflammation, the immune response, hypoxia, and tumorigenesis.
Figure 5.  The role of epigenetic factors in the pathogenesis of AMD. Interaction among environmental, genetic, and epigenetic factors may determine initiation of the pathogenesis of AMD. Environmental factors may contribute to the alteration of epigenetic factors, changes in epigenetic mechanisms may induce abnormal gene expression through crosstalk with the genome. On the other hand, genetic alterations, such as single nucleotide polymorphisms, may affect epigenetic factors. Furthermore, there is an interplay among epigenetic regulation pathways, suggesting that AMD is a complex disease. An aberration of genome transcription that is related to AMD is regulated by both genetic and epigenetic factors.
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