Abstract
Diabetic retinopathy (DR) is one of the main causes of vision loss in middle-aged economically active people. Modifiable (i.e., hyperglycaemia, hypertension, hyperlipidaemia, obesity, and cigarette smoke) and non-modifiable factors (i.e., duration of diabetes, puberty, pregnancy and genetic susceptibility) are involved in the development of DR. Epigenetic mechanisms, modulating the oxidative stress, inflammation, apoptosis, and aging, could influence the course of DR. Herein, we conducted a systematic review of observational studies investigating how epigenetics affects type 2 diabetes retinopathy (T2DR). A total of 23 epidemiological studies were included: 14 studies focused on miRNA, 4 studies on lnc-RNA, one study on both miRNA and lnc-RNA, and 4 studies on global or gene-specific DNA methylation. A direct relation between the dysregulation of miR-21, miR-93, and miR-221 and FPG, HbA1c, and HOMA-IR was identified. A panel of three miRNAs (hsa-let-7a-5p, hsa-miR-novel-chr5_15976, and hsa-miR-28-3p) demonstrated a good sensitivity and specificity for predicting T2DR. Little evidence is available regarding the possible role of the long non-coding MALAT1 dysregulation and MTHFR gene promoter hypermethylation. Despite these initial, encouraging findings potentially suggesting a role of epigenetics in T2DR, the use in clinical practice for the diagnosis and staging of this complication encounters several difficulties and further targeted investigations are still necessary.
Highlights
Diabetic retinopathy (DR) is a specific microvascular complication of diabetes mellitus (DM) which results in the damage of small blood vessels and neurons of the retina
Epigenetic mechanisms—including DNA methylation, histone modifications, and miRNAs and long non-coding RNA regulation—contribute to the dysregulation of signalling pathways involved in oxidative stress, inflammation, apoptosis, and aging, and modulate the expression of several key genes in DM [11,12]
Both preclinical and clinical studies in diabetic patients provided strong evidence concerning the contribution of histone modifications, post-transcriptional RNA regulation, and DNA methylation in diabetes-related microvascular complications by regulating molecular pathways involved in the pathogenesis of these complications
Summary
Diabetic retinopathy (DR) is a specific microvascular complication of diabetes mellitus (DM) which results in the damage of small blood vessels and neurons of the retina It is one of the leading causes of vision loss in middle-aged economically active people, accounting for 4.8% of the number of cases of blindness (37 million) worldwide [1]. Epigenetic mechanisms—including DNA methylation, histone modifications, and miRNAs and long non-coding RNA (lnc-RNA) regulation—contribute to the dysregulation of signalling pathways involved in oxidative stress, inflammation, apoptosis, and aging, and modulate the expression of several key genes in DM [11,12] Both preclinical and clinical studies in diabetic patients provided strong evidence concerning the contribution of histone modifications, post-transcriptional RNA regulation, and DNA methylation in diabetes-related microvascular complications by regulating molecular pathways involved in the pathogenesis of these complications. We conducted a systematic review to summarise current evidence from observational studies investigating the relationship between DR and epigenetic mechanisms
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