Frontiers in endocrinology · 2026
Profiling dysregulated circRNA expression in diabetic retinopathy: elucidating putative mediators via a streptozotocin-induced mouse model.
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Zhang Conghui, Feng Le, Li Qian, Cui Hongping
Аннотация
BACKGROUND: Circular RNAs (circRNAs), a conserved class of non-coding RNAs, are hypothesized to play functional roles in diabetic retinopathy (DR), yet their expression landscape and molecular involvement in retinal tissue remain poorly defined.
METHODS: A streptozotocin-induced diabetic mouse model (C57BL/6J, male, n=40) was established, with diabetes confirmed by persistent hyperglycemia (fasting blood glucose >300 mg/dL). Retinal function was assessed by electroretinography (ERG) and vascular pathology by fluorescein fundus angiography (FFA) at 12 weeks post-induction. Retinal circRNA profiles were obtained via microarray analysis. Bioinformatic tools were used to predict circRNA-miRNA interactions, and Gene Ontology (GO) analysis was applied to annotate potential target genes. Differential expression of selected circRNAs was validated by quantitative PCR (qPCR).
RESULTS: Diabetic mice exhibited sustained hyperglycemia, reduced body weight, significant declines in ERG a and b wave amplitudes, and early microangiopathy evident on FFA. Microarray profiling identified 21 dysregulated circRNAs (3 upregulated, 18 downregulated), classified as antisense, exonic, intronic, or intragenic. Bioinformatics reconstruction revealed a circRNA-miRNA network with shared microRNAs (miRNAs), and GO enrichment highlighted processes including transcriptional regulation and cancer-related signaling. qPCR confirmed the expression changes of four circRNAs. Cross-species alignment showed high sequence homology between four murine circRNAs and human orthologs.
CONCLUSION: This study identifies 21 conserved circRNAs with altered expression in the diabetic retina, supporting their potential role as competitive endogenous RNAs (ceRNAs) and implicating them in DR pathogenesis.
METHODS: A streptozotocin-induced diabetic mouse model (C57BL/6J, male, n=40) was established, with diabetes confirmed by persistent hyperglycemia (fasting blood glucose >300 mg/dL). Retinal function was assessed by electroretinography (ERG) and vascular pathology by fluorescein fundus angiography (FFA) at 12 weeks post-induction. Retinal circRNA profiles were obtained via microarray analysis. Bioinformatic tools were used to predict circRNA-miRNA interactions, and Gene Ontology (GO) analysis was applied to annotate potential target genes. Differential expression of selected circRNAs was validated by quantitative PCR (qPCR).
RESULTS: Diabetic mice exhibited sustained hyperglycemia, reduced body weight, significant declines in ERG a and b wave amplitudes, and early microangiopathy evident on FFA. Microarray profiling identified 21 dysregulated circRNAs (3 upregulated, 18 downregulated), classified as antisense, exonic, intronic, or intragenic. Bioinformatics reconstruction revealed a circRNA-miRNA network with shared microRNAs (miRNAs), and GO enrichment highlighted processes including transcriptional regulation and cancer-related signaling. qPCR confirmed the expression changes of four circRNAs. Cross-species alignment showed high sequence homology between four murine circRNAs and human orthologs.
CONCLUSION: This study identifies 21 conserved circRNAs with altered expression in the diabetic retina, supporting their potential role as competitive endogenous RNAs (ceRNAs) and implicating them in DR pathogenesis.