Diabetic Retinopathy: Are lncRNAs New Molecular Players and Targets?

Abstract

The growing incidence of diabetes mellitus worldwide implies the increasing prevalence of several related macro- (e.g., hypertension and atherosclerosis) and micro-vascular (e.g., nephropathy and retinopathy) complications. Notably, diabetic retinopathy (DR) is the leading cause of blindness in older diabetic patients and can occur with different degrees of severity. Chronic hyperglycemia is the main determinant of the functional damage of retinal cells. The oxidative stress, inflammatory factors and vascular endothelial growth factor signaling have been widely reported as contributors of DR onset and progression, and an emerging role has been described for different classes of non-coding RNA, including several long non-coding RNAs (lncRNAs). Here, we report the main results of all research articles (i.e., 150) listed on PubMed database from 2014 to 2022 regarding the putative role of lncRNAs in DR, including small nucleolar RNA host genes (SNHGs). Particularly, in this review we describe all lncRNAs and SNHGs with altered expression in DR and related contexts, discussing their association with DR outcomes, their mechanism of action related to DR, the molecular/functional effects, as well as the biological and experimental contexts. Thus, herein we provide an overview of the current state of knowledge regarding the putative involvement of 50 lncRNAs and SNHGs in the pathogenesis of DR, highlighting their potential as therapeutic targets or biomarkers for improving the clinical management of DR.

Long Non-Coding RNAs and Proliferative Retinal Diseases

“…The maternally expressed gene 3 (MEG3) is a tumor repressor lncRNA [ 38 ]. The expression of lncRNA-MEG3 was decreased in endothelial cells subjected to hydrogen peroxide, and in streptozotocin-induced diabetic mice [ 39 ]. Depleting lncRNA-MEG3 increases the phosphorylation of PI3K and Akt, suggesting its role in angiogenesis.…”

The Sweet Side of HIPK2

“…Thus, HG-increased HIPK2 expression correlates One of the complications of diabetes is diabetic retinopathy (DR), which is also the primary cause of blindness in the world [106]. An interesting link between HIPK2 and DR has been depicted due to HIPK2 regulation by microRNA (miRNA), which is usually involved in DR vascular complications [107]. Taking advantage of a previous study in which the authors found that miR-423-5p levels are elevated in the plasma of DR patients [108], the authors, following this, evaluated the role of HG in this regulation.…”

Potential roles of lncRNA MALAT1-miRNA interactions in ocular diseases

“…Extensive research has revealed the dysregulation of various ncRNAs, including microRNAs (miRNAs), circular RNAs (circRNAs), and long non‐coding RNAs (lncRNAs), in conditions such as glaucoma, cataract, diabetic retinopathy, and ocular tumors (Rong et al 2021; Zhang et al 2020a). These ncRNAs have been shown to impact important cellular processes, including angiogenesis, inflammation, cell proliferation, and apoptosis, which are critical in the development and progression of ocular diseases (Cataldi et al 2021). Understanding the involvement of ncRNAs in ocular diseases holds promise for the development of novel diagnostic tools and therapeutic strategies targeting these ncRNA molecules (Shi et al 2023).…”