Epigenomic signatures in age-related macular degeneration: Focus on their role as disease modifiers and therapeutic targets

Abstract

Epigenetics is characterized by molecular modifications able to shape gene expression profiles in response to inner and external stimuli. Therefore, epigenetic elements are able to provide intriguing and useful information for the comprehension and management of different human conditions, including aging process, and diseases. On this subject, Age-related Macular Degeneration (AMD) represents one of the most frequent age-related disorders, dramatically affecting the quality of life of older adults worldwide. The etiopathogenesis is characterized by an interplay among multiple genetic and non-genetic factors, which have been extensively studied. Nevertheless, a deeper dissection of molecular machinery associated with risk, onset, progression and effectiveness of therapies is still missing. In this regard, epigenetic signals may be further explored to disentangle disease etiopathogenesis, the possible therapeutic avenues and the differential response to AMD treatment. This review will discuss the epigenomic signatures mostly investigated in AMD, which could be applied to improve the knowledge of disease mechanisms and to set-up novel or modified treatment options.

WARE: Wet AMD Risk-Evaluation Tool as a Clinical Decision-Support System Integrating Genetic and Non-Genetic Factors

“…It is well-known that a complex interplay among genetic and non-genetic factors (smoking habits, lifestyle, aging, diet, family history) contributes to the onset of AMD [ 8 , 9 , 10 , 11 ]. The impact of these risk factors has been extensively explored among worldwide populations, highlighting prominent differences [ 12 ].…”

Relationship between Nutrition, Lifestyle, and Neurodegenerative Disease: Lessons from ADH1B, CYP1A2 and MTHFR

“…In particular, epigenetic elements are able to shape and modulate gene expression in response to external stimuli (age, environment/lifestyle, diet, and disease condition). To date, at least three epigenetic mechanisms are known to impact gene expression, namely DNA methylation, histone modification, and non-coding-RNAs [ 64 ].…”

“…In addition, miRNAs can be detected in several body fluids, such as blood, saliva, urine, and cerebrospinal fluid. In the last decades, several research efforts have been made to disclose the role of miRNAs in neurogenesis and neurodegeneration [ 64 ]. Actually, miRNAs are known to be involved in the production and degradation of toxic proteins accumulating in the brain as well as in neuronal death.…”

“…In addition, they can be expressed as a result of cellular or tissue damage, aging, and dysfunction of pro-survival proteins. Currently, miRNA-29a, miRNA-29b, miRNA-34a, miRNA-103, miRNA-107, miRNA-125a, miRNA-146a, miR-155, miR-196a, miR-499a, and many others have been involved in neuroinflammation, mitochondrial dysfunction, synaptic transmission, endosomal–lysosomal dysfunction, apoptosis, oxidative stress, and membrane and intracellular trafficking [ 64 ].…”