Diabetic Retinopathy, lncRNAs, and Inflammation: A Dynamic, Interconnected Network

Abstract

Diabetic retinopathy (DR) is reaching epidemic levels globally due to the increase in prevalence of diabetes mellitus (DM). DR also has detrimental effects to quality of life, as it is the leading cause of blindness in the working-age population and the most common cause of vision loss in individuals with DM. Over several decades, many studies have recognized the role of inflammation in the development and progression of DR; however, in recent years, accumulating evidence has also suggested that non-coding RNAs, especially long non-coding (lncRNAs), are aberrantly expressed in diabetes and may play a putative role in the development and progression of DR through the modulation of gene expression at the transcriptional, post-transcriptional, or epigenetic level. In this review, we will first highlight some of the key inflammatory mediators and transcription factors involved in DR, and we will then introduce the critical roles of lncRNAs in DR and inflammation. Following this, we will discuss the implications of lncRNAs in other epigenetic mechanisms that may also contribute to the progression of inflammation in DR.

Keywords: DNA methylation; diabetic retinopathy; epigenetics; histone modifications; inflammation; lncRNAs; miRNAs.

Figure 1

A schematic depicting the dynamic, coordinated network involving epigenetic modifications in inflammation during DR. Several key epigenetic mechanisms are involved in the progression of inflammation. LncRNAs may serve as critical regulators of inflammation, through their effects on other epigenetic mechanisms, such as DNA methylation, histone modifications, and the activity of other non-coding RNAs (i.e., miRNAs). Furthermore, since the molecular network is heavily coordinated, several individual components of this network may inter-regulate one another, indicated by the double arrows in the figure, and future research should keep these interactions in mind.