Regulatory role of miRNA‑23a in diabetic retinopathy

Abstract

The present study aimed to investigate the expression of microRNA (miRNA)-23a in blood and tear samples from diabetic retinopathy (DR) patients. Blood and tear samples were obtained from 33 patients with proliferative DR. Additionally, a rat model of DR was established. Reverse transcription-quantitative PCR was used to determine vascular endothelial growth factor (VEGF) mRNA and miRNA-23a expression levels, while ELISA and western blot analysis were performed to determine protein expression levels. Bioinformatics analysis and dual luciferase reporter assay were used to predict and validate the interaction between miRNA-23a and VEGF and cell proliferative ability was assessed with the MTT assay. In comparison to control patients VEGF mRNA and protein expression levels were significantly elevated in the blood and tear samples from patients with DR, while the expression level of miRNA-23a was significantly reduced. In blood and retinal tissues from a rat model of DR, the mRNA and protein expression levels of VEGF were significantly increased, while the miRNA-23a expression level was significantly decreased relative to controls. Dual luciferase reporter assay showed that miRNA-23a bound to the 3'-untranslated region (UTR) of VEGF. Moreover, over-expression of miRNA-23a significantly reduced the expression level of VEGF and the proliferative activity of human retinal microvascular endothelial cells. The elevated VEGF expression in the blood and tears of patients with DR may be related to the reduced miRNA-23a expression. miRNA-23a may regulate microvascular growth at the retina via VEGF and contribute to DR progression.

LncRNA XIST promotes neovascularization in diabetic retinopathy by regulating miR-101-3p/VEGFA

“…Circular RNA COL1A2 contributes to HG-induced proliferation, migration, and vascular permeability in HRMECs and retinal angiogenesis in mice with diabetes by competing with VEGF mRNA for binding to miR-29b ( 30 ). There are many other miRNAs, such as miR-15b, miR-23a, miR-205-5p, and miR-150-5p, which directly interact with VEGF in retinal endothelial cells and are involved in angiogenesis in DR ( 31 - 34 ). This study identified miR-101-3p as a direct regulator of VEGFA in HRMECs.…”

Tear Film MicroRNAs as Potential Biomarkers: A Review

“…Tear miRNA composition has been shown to be altered in DR patients. Sun et al found that miR-23a expression was decreased in the tears and serum of patients with type 2 diabetes or pre-diabetes compared to controls [ 18 ]. This is intriguing as miR-23a has been linked to a potential inhibitory role on VEGF, an important factor in the development of DR and blood vessel growth [ 114 , 115 ].…”

“…Advances in miRNA quantitation, paired with the simple, non-invasive collection methods of tears [ 13 ], entice mass participant collection [ 14 ] and physician engagement [ 15 ], which is essential for biomarker validation. Moreover, the importance of studying the relationship between tear composition and ocular health has become more apparent in recent years, and a multitude of studies have reported variations in tear miRNA content across different pathologies [ 12 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. The cohesive relationship between miRNAs, the tear film, and health makes tear miRNAs pertinent options as noninvasive and low-cost diagnostic markers for numerous pathologies [ 13 , 23 , 24 , 25 ].…”

“…The cohesive relationship between miRNAs, the tear film, and health makes tear miRNAs pertinent options as noninvasive and low-cost diagnostic markers for numerous pathologies [ 13 , 23 , 24 , 25 ]. Several studies have identified tear miRNAs as potential biomarkers for ocular diseases including diabetic retinopathy [ 18 , 26 , 27 ], Sjögren’s syndrome [ 19 ], glaucoma [ 20 , 28 ], dry eye disease [ 21 , 29 , 30 ], diabetic macular edema [ 12 ], herpes epithelial keratitis [ 22 ], and vernal keratoconjunctivitis [ 31 ]. Furthermore, tear miRNA alterations have been associated with some non-ocular diseases, such as Alzheimer’s [ 16 ] and metastatic breast cancer [ 32 ].…”

Noncoding RNAs Are Promising Therapeutic Targets for Diabetic Retinopathy: An Updated Review (2017–2022)

“…Moreover, plasma miR-26a-5p levels and retinal nerve fiber layer thickness are positively correlated; this may be a potential biomarker for early-stage DR [ 55 ]. Sun et al found that miRNA-23a levels are significantly decreased in the blood and tears of patients with DR. Overexpression of miRNA-23a significantly inhibits retinal microvascular EC proliferation by reducing VEGF expression [ 56 ]. miR-1281 was found to be considerably overexpressed in serum samples from patients with DR and could, therefore, be a new target in treating DR [ 57 ].…”