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A research study of methylation as an epigenomic biomarker in rare ophthalmic diseases

Researchers based in Queen’s University Belfast (QUB), UK have reported a systematic review of differential methylation in rare ophthalmic diseases.  Methylation of key epigenomic biomarkers, such as DNA methylation or histone modification, has identified a review of at least eight studies showing pathogenic biomarkers for ophthalmic disease.  These ophthalmic disorders include brittle cornea syndrome, choroideraemia, FECD (Fuchs endothelial corneal dystrophy), retinitis pigmentosa (RP), Retinopathy of prematurity and others.  Importantly, DNA methylation may evaluate a potential novel therapeutic target in two studies of RP with methyltransferase inhibitors (decitabine and 3-Deazaneplanocin A) which has now reported to reduce RP phenotype progression.  Further epigenomic research may likely uncover new diagnostic and therapeutic opportunities for ophthalmic rare disease.


Rare diseases in the European Union are defined as conditions which affect fewer than 1 in 2,000 people, while in the USA, rare diseases are defined as conditions which affects less than 200,000 people in the population.  According to researchers, rare diseases estimate to affect 3.5 million people in the UK, 30 million people across Europe, 25–30 million people in the USA and 350 million people worldwide.  The National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE), created by the National Eye Institute, has reported >130 publications of studies researching genetic mutations in rare ophthalmic diseases however, there is a limited information for research on methylation studies among rare ophthalmic diseases.  This compares to research on epigenetic markers of common diseases, including diabetic retinopathy, age-related macular degeneration and cataracts.  The current research in Queen’s University has proposed to assess the potential for methylation as an epigenomic marker of rare ophthalmic disease and this potential may contribute to early diagnosis, management, reduction of vision loss and the identification of novel therapeutic targets.


The current systematic research screened 132 sources which finally analysed 14 papers having met the relevant inclusion/exclusion criteria for review. As highlighted, aberrant methylation was established as a pathogenic biomarker of ophthalmic disease in eight studies and also reported DNA methylation as a potential novel therapeutic target in two studies of RP.  Commenting on the review, the researchers stated that, “patients with rare ophthalmic conditions can face difficulties obtaining a diagnosis, and treatment for their condition is often limited which can have severely detrimental impacts for a patient’s vision. Therefore, there is a need for improving our understanding of these conditions, to aid diagnosis, provide prognoses or identify therapeutic targets which could correct or halt degeneration in patients with rare eye dysfunction.”  Finally, the systematic review study concluded that “epigenomic markers such as DNA methylation with genomic analysis has the potential to aid diagnosis, limit loss of patient vision and ultimately improve patient independence and quality of life.”