Epigenetic Mechanisms of the Aging Human Retina

Abstract

Degenerative retinal diseases, such as glaucoma, age-related macular degeneration, and diabetic retinopathy, have complex etiologies with environmental, genetic, and epigenetic contributions to disease pathology. Much effort has gone into elucidating both the genetic and the environmental risk factors for these retinal diseases. However, little is known about how these genetic and environmental risk factors bring about molecular changes that lead to pathology. Epigenetic mechanisms have received extensive attention of late for their promise of bridging the gap between environmental exposures and disease development via their influence on gene expression. Recent studies have identified epigenetic changes that associate with the incidence and/or progression of each of these retinal diseases. Therefore, these epigenetic modifications may be involved in the underlying pathological mechanisms leading to blindness. Further genome-wide epigenetic studies that incorporate well-characterized tissue samples, consider challenges similar to those relevant to gene expression studies, and combine the genome-wide epigenetic data with genome-wide genetic and expression data to identify additional potentially causative agents of disease are needed. Such studies will allow researchers to create much-needed therapeutics to prevent and/or intervene in disease progression. Improved therapeutics will greatly enhance the quality of life and reduce the burden of disease management for millions of patients living with these potentially blinding conditions.

Epigenetics in age-related macular degeneration: new discoveries and future perspectives

“…It is the epigenome that contributes substantially to the organisation of a functional retina, through fine-tuning gene expression patterns. This leads to the generation of great diversity in different cell types and in the molecular machinery, in both the developing and the ageing retina [11]. Establishing control of gene expression, epigenetic signals have been found to be related to retinal development and moreover to retinal disease, and specific epigenetic changes to be associated with the most devastating complex eye disease in the elderly population: AMD [12].…”

“…The addition of a methyl group to the C5 position of cytosine bases, that are followed by guanosine bases within the DNA sequence (5′-CpG-3′), is associated with the repression of gene expression. Unmethylated CpG islands are a feature of actively expressed genes and unexpressed genes generally have methylated CpG islands near their transcription start sites [11].…”

“…Writers can add, readers can interpret and erasers can remove epigenetic modifications on chromatin. Histone acetyltransferases add, and histone deacetylases (HDAC) remove acetyl groups to and from histone lysine residues, respectively [11]. HDAC inhibitors have been utilised in clinical trials to treat cancer and could be used for the treatment of retinal degenerative diseases [57].One class of HDACs known as sirtuins has been implicated in the ageing process [58].…”

Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors

“…Therapeutics that can prevent the progression from early to intermediate and/or from intermediate to advanced stages of the disease are greatly needed to alleviate the profound detrimental impacts of vision loss; elucidation of the molecular mechanisms involved in the etiology and progression of AMD, taking into account evidence from gene expression, epigenetic, molecular, and biochemical studies to complement genetic epidemiological studies, will be necessary to accomplish this goal [22–25]. …”

“…AMD is a complex disease with many genetic and environmental factors, as well as interactions among these many factors, which influence susceptibility to risk [25–39]. Some of these epidemiological risk factors for AMD can be modified, and include body-mass index (BMI), smoking tobacco, diet, and blood lipid and cholesterol levels [35].…”