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Open Access Basic Research Issue
Angiogenesis-RNA modification in diabetic retinopathy: biomarkers and targets
International Journal of Ophthalmology 2026, 19(10): 1914-1928
Published: 18 October 2026
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AIM

To identify biomarkers and potential therapeutic targets related to angiogenesis and RNA modification in diabetic retinopathy (DR).

METHODS

The Gene Expression Omnibus (GEO) datasets GSE12610, GSE87433, and GSE111465, which contain retinal samples from diabetic and normal mice, were analyzed to identify differentially expressed genes (DEGs). The DEGs were then intersected with angiogenesis- and RNA modification-related genes (A&RMRGs) obtained from GeneCards and other databases to identify differentially expressed A&RMRGs in DR. Hub genes were subsequently identified from the protein-protein interaction (PPI) network built on the enrichment results. Their diagnostic value was then estimated by receiver operating characteristic (ROC) analysis, and their expression levels were tested for associations with immune cell infiltration. Regulatory networks of hub genes were constructed using MicroRNA Target Prediction Database (miRDB), ChIPBase, and the Comparative Toxicogenomics Database (CTD). To validate the bioinformatic findings, hub gene transcript levels were quantified with reverse transcription quantitative polymerase chain reaction (RT-qPCR) in high-glucose-treated rat retinal microvascular endothelial cells (rRMECs).

RESULTS

Forty-two A&RMRGs showed differential expression in the diabetic retina, with Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment implicating RNA modification and immune-inflammatory regulation, alongside Gene Set Enrichment Analysis (GSEA) evidence of activated RNA-silencing and fatty-acid-transport programs and suppressed neuronal and retinoid-cycle programs. Seven hub genes (Wdr3, Crebbp, Sdad1, Stat3, Gnl2, Nhp2, and Hsp90aa1) were selected, all of them were upregulated in DR. The DR retina showed higher levels of central memory CD8+ T cells and lower levels of monocytes, Tregs, and CD56bright natural killer (NK) cells. Monocyte infiltration was inversely associated with Stat3 expression (r=-0.604, P<0.001), and central memory CD8+ T cell levels were positively associated with Nhp2 expression (r=0.539, P=0.003). A total of 60 miRNAs, 43 transcription factors (TFs), and 47 drugs may regulate RNA modification of angiogenesis-associated genes in DR. Gnl2 [area under the ROC curve (AUC)=0.914, 95% confidence interval (CI):0.810–1.000) and Stat3 (AUC=0.964, 95%CI: 0.892–1.000) showed high diagnostic value. Exposure of rRMECs to high glucose led to a marked rise in Stat3 expression and a fall in Sdad1, leaving the transcript levels of the remaining five hub genes unchanged.

CONCLUSION

These findings identify Stat3 as a point of convergence between RNA modification, immune dysregulation, and angiogenesis, nominating the hub genes as candidate biomarkers and the associated drug–gene interactions as repurposing leads.

Open Access Bibliometric Research Issue
Global trends in retinal vein occlusion studies from 2004 to 2023: a bibliometric analysis
International Journal of Ophthalmology 2025, 18(9): 1759-1769
Published: 18 September 2025
Abstract PDF (2.1 MB) Collect
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AIM

To analyse the research status and explore global trends in retinal vein occlusion (RVO) studies.

METHODS

Publications related to RVO from 2004 to 2023 were extracted from the Web of Science Core Collection (WoSCC). Variables including the number of publications, as well as countries, organizations, authors, journals, references and keywords were analysed using Bibliometrix-BilioShiny. Data visualization was performed using VOSviewer and CiteSpace.

RESULTS

A total of 4848 publications were retrieved, and generally, the number of publications showed an overall increasing trend with slight fluctuations over the past 20y. The country with the most publications was the United States. The journal with the most publications was Retina, and the most cited journal was Ophthalmology. The most prolific organization was the University of California, Los Angeles. The most productive author was Noma H, and the most cited author was Campochiaro PA. The top co-cited references mainly focused on the prevalence of RVO and the therapies used in clinical trials. According to the co-occurrence analysis, the keywords formed 3 clusters: 1) risk factors and pathogenesis of RVO, 2) treatments of RVO, and 3) imaging diagnosis of RVO. Anti-vascular endothelial growth factor (VEGF) treatments and artificial intelligence have recently become popular research topics.

CONCLUSION

Bibliometric analysis of the research status and trends of RVO could provide researchers and clinicians with valuable insights for further collaboration, future research directions, and clinical practice.

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