title: The role of epigenetics in age-related macular degeneration.
abstract: It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcriptional potential of a cell, which are not necessarily heritable but remains to be defined in the future. Increasing understanding of the significance of common and rare genetic variants and their relationship to epigenetics and environmental influences may help in establishing methods to assess the risk of AMD. This in turn may allow new therapeutic interventions for the leading cause of central vision impairment in patients over the age of 50 years in developed countries. Search strategy We searched the MEDLINE/PubMed database following MeSH suggestions for articles including the terms: 'ocular epigenetic mechanisms', 'human disease epigenetics', and 'age-related macular degeneration genetics'. The headline used to locate related articles in PubMed was 'epigenetics in ocular disease', and to restrict search, we used the headlines 'DNA methylation in age related macular degeneration', 'altered gene expression in AMD pathogenesis'. A manual search was also based on references from these articles as well as review articles.
authors.affiliation: Southampton Eye Unit, Southampton University Hospital, Southampton, UK.
authors.forename: M
authors.initials: M
authors.lastname: Gemenetzi
authors.affiliation: 1] Southampton Eye Unit, Southampton University Hospital, Southampton, UK [2] Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Lotery
mesh_terms: D044127:Epigenesis, Genetic / Q000502:physiology*; D015870:Gene Expression; D059647:Gene-Environment Interaction; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*