Altered Expressions of Transfer RNA-Derived Small RNAs and microRNAs in the Vitreous Humor of Proliferative Diabetic Retinopathy

Abstract

PurposeWe sought to reveal the expression profiles of transfer RNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) in the vitreous humor of patients with proliferative diabetic retinopathy (PDR).MethodsVitreous humor samples were obtained from PDR patients and a control group for this study. Sequencing of small RNAs was conducted to assess the expression profiles of tsRNAs and miRNAs in both groups, which was followed by validation using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Bioinformatics analyses were conducted to predict the target genes and their potential biological functions and signaling pathways.ResultsA total of 37 tsRNAs and 70 miRNAs with significant differences were screened out from the vitreous humor samples of PDR patients compared to controls. Following validation by RT-qPCR, the target genes of the validated tsRNAs and miRNAs were predicted, and Gene Ontology analysis indicated that the target genes of the tsRNAs were most enriched in the cellular macromolecule metabolic process, cytoplasm, and ion-binding, while those of the miRNAs were most abundant in the regulation of major metabolic process, cytoplasm, and protein-binding. In addition, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the target genes of said tsRNAs and miRNAs were most enriched in the adenosine monophosphate-activated protein kinase signaling pathway and Th17 cell differentiation, respectively.ConclusionsThe present study identified altered tsRNAs and miRNAs in vitreous humor samples of PDR patients, which may play important roles in the pathogenesis of PDR and could be considered potential therapeutic targets in the treatment of PDR.

piRNAs in the human retina and retinal pigment epithelium reveal a potential role in intracellular trafficking and oxidative stress

“…The alignment of piRNAs with other ncRNAs revealed their potential crosstalk in the regulation of development, stress and circadian rhythm. Several studies have shown the correlation between stress and differentially expressed tsRNAs with the pathological implications observed during the course of a disease condition, including DR. 88,89 In line with this, hypoxic stress may alter the expression of the 3rd motif containing td-piRNAs, which in turn can regulate the ocular pathogenesis during DR and other related disorders. On the other hand, the presence of sd-piRNAs could be of importance during the developmental stage of the retina, which needs to be validated through functional experiments.…”

Biomarker potential of vitreous microRNA in retinal disease: a meta-analysis

“…In contrast, Gomaa et al showed that miR-200b was elevated in PDR but it did not correlate with vitreous levels of VEGF (47). Yang et al identified seven miRNA that were elevated in PDR, and KEGG analysis showed that the target genes of these miRNA were most enriched in the Th17 cell differentiation pathway (48). Notably, interleukin-17, which is produced by Th17 cells, has been shown to promote retinal neovascularization through multiple mechanisms (49–51).…”

Advances and Perspectives in Relation to the Molecular Basis of Diabetic Retinopathy—A Review

“…In addition, it was revealed in the study performed on rats with induced diabetes that miRNA-200b in DR diseases is lower than in the healthy group [123]. According to the vitreous humor, there were studies suggesting changes in several particle concentrations in PDR groups: miRNA-125, miRNA-21, hsa-miRNA-6734-5p, and hsa-miRNA-1297 [124,125]. MiRNAs, such as hsa-miRNA-3184-3p, hsa-miRNA-24-3p, and hsa-miRNA-197-3p, were assessed to be upregulated in the vitreous humor of PDR patients; furthermore, anti-VEGFfactor administration led to lower expression of those particles [124].…”

“…According to the vitreous humor, there were studies suggesting changes in several particle concentrations in PDR groups: miRNA-125, miRNA-21, hsa-miRNA-6734-5p, and hsa-miRNA-1297 [124,125]. MiRNAs, such as hsa-miRNA-3184-3p, hsa-miRNA-24-3p, and hsa-miRNA-197-3p, were assessed to be upregulated in the vitreous humor of PDR patients; furthermore, anti-VEGFfactor administration led to lower expression of those particles [124]. However, vitreous humor parameter measurements are not easy to perform.…”