Abstract
Purpose To characterize the microRNA (miRNA) expression profiles in the retinas of mice with oxygen-induced retinopathy by RNA sequencing and to ascertain miRNAs associated with retinal neovascularization. Methods Retina samples were obtained from 3 groups (6 retinas/group) of OIR mice and normal mice at P17. RNA was isolated from 24 retina samples and then detected on an Illumina HiSeq. Twelve retina samples were used for quantitative polymerase chain reaction to validate the RNA sequencing. Bioinformatics analyses were performed. Result The RNA sequence showed that 565 miRNAs were detected in the retina of OIR mice and 583 miRNAs in the retina of normal control mice. A total of 553 miRNAs were expressed in both groups. Thirty-eight miRNAs showed altered expression in both groups (p ≤ 0.05). Compared with the control group, 2 miRNAs were significantly upregulated in the OIR group, while 36 miRNAs were significantly downregulated. Meanwhile, 2 candidate miRNAs (miR-181a-5p and miR-21a-5p) with significant differences in miRNA expression (p < 0.01) were selected for validation. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm the relative expression of the two miRNAs. Bioinformatics analyses showed that pathways involved in ischemic retinopathy (such as TGF-β, Ras, Hippo, PI3K-Akt, VEGF, and HIF-1 signaling pathways) were enriched. Conclusions Our study provided an overall view of miRNA profiling in the OIR retina. These miRNA profiles provide a valuable framework for the potential therapy of retinal angiogenesis.
Highlights
Ischemic retinopathy (IR) is defined as abnormal neovascularization of the retina followed by ischemia, which is the most common vision-threatening complication in many diseases, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retina vein occlusion (RVO) [1, 2]
Alterations in miRNA expressions were validated by Quantitative real-time polymerase chain reaction (qRT-PCR). e upregulation and downregulation of miRNAs may provide an improved understanding of the mechanism of ischemic retinopathy
Discussion miRNAs play a key role in cell function and biological development, such as neurogenesis, metabolism, inflammation, and angiogenesis [22]
Summary
Ischemic retinopathy (IR) is defined as abnormal neovascularization of the retina followed by ischemia, which is the most common vision-threatening complication in many diseases, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retina vein occlusion (RVO) [1, 2]. MicroRNAs (miRNAs) are endogenous noncoding RNAs with a length of about 22 nucleotides which involve in the posttranscriptional regulation of gene expression [10] and regulate a wide range of physiological and pathological processes [11, 12]. Ey are key regulators of vessel development [13] and contribute to the formation of pathological RNV [9, 14]. Alterations in miRNA expression have been studied in different signaling pathways involved in the progression and pathogenesis of RNV. Identifying retinal miRNAs differentially expressed genes in RNV may reveal potentially effective miRNAs and help to clarify their pathogenesis and mechanisms. Erefore, in this study, we used RNA sequencing technology to evaluate the miRNA profiles in OIR retinas at P17 compared with the normal retinas and to investigate which miRNA expression was altered. Alterations in miRNA expressions were validated by qRT-PCR. e upregulation and downregulation of miRNAs may provide an improved understanding of the mechanism of ischemic retinopathy
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