Study on the Regulatory Mechanism of tsRNA-Gln-i-0095 in Retinal Ischemia-Reperfusion Injury

Academic Background

Retinal ischemia-reperfusion (I/R) injury is a critical pathological mechanism in various ocular diseases, including glaucoma, central retinal vein occlusion, and retinopathy of prematurity. I/R injury leads to the death of retinal ganglion cells (RGCs), resulting in vision loss. Although current treatment strategies, such as anti-vascular endothelial growth factor (VEGF) drugs and anti-glaucoma medications, exist, their clinical efficacy remains limited. Therefore, in-depth research into the molecular mechanisms of I/R injury and the identification of new therapeutic targets are of great significance.

In recent years, transfer RNA-derived small RNAs (tsRNAs) have garnered increasing attention as novel gene regulatory molecules. tsRNAs play important roles in various biological processes and diseases, but their specific functions in retinal I/R injury are not yet fully understood. This study aims to explore the role of tsRNA-Gln-i-0095 in retinal I/R injury and its potential therapeutic value.

Source of the Paper

This paper was co-authored by Ying Zhang, Yan Ma, Yu-Ke Ji, and others, with the research team affiliated with the Affiliated Eye Hospital of Nanjing Medical University, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, and Eye & ENT Hospital of Fudan University. The paper was published in 2025 in the journal Cell Communication and Signaling, titled “Co-targeting of glial activation and inflammation by tsRNA-Gln-i-0095 for treating retinal ischemic pathologies.”

Research Process and Results

1. Expression Changes of tsRNA-Gln-i-0095 in I/R Injury

The study first detected the expression changes of tsRNA-Gln-i-0095 in a retinal I/R injury model using qRT-PCR. The results showed that tsRNA-Gln-i-0095 was significantly upregulated after I/R injury, particularly in Müller cells. Additionally, an in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model confirmed the upregulation of tsRNA-Gln-i-0095 in Müller cells.

2. Effects of tsRNA-Gln-i-0095 on Müller Cell Function

To further investigate the function of tsRNA-Gln-i-0095, the research team modulated its expression in Müller cells by transfecting tsRNA-Gln-i-0095 mimics and inhibitors. The results showed that overexpression of tsRNA-Gln-i-0095 significantly enhanced the viability and proliferation of Müller cells, while its inhibition led to increased cell apoptosis. Furthermore, overexpression of tsRNA-Gln-i-0095 promoted the release of inflammatory cytokines IL-1β, IL-6, and TNF-α.

3. Protective Effects of tsRNA-Gln-i-0095 on RGCs

Through co-culture experiments, the research team found that overexpression of tsRNA-Gln-i-0095 exacerbated RGC apoptosis under OGD/R conditions, while its inhibition significantly alleviated RGC damage. In vivo experiments further confirmed that inhibition of tsRNA-Gln-i-0095 improved RGC survival and reduced retinal neuronal injury.

4. Molecular Mechanism of tsRNA-Gln-i-0095

The research team confirmed the interaction between tsRNA-Gln-i-0095 and the Ago2 protein through RNA immunoprecipitation (RIP) and RNA pull-down assays, suggesting that it may regulate gene expression through a miRNA-like mechanism. Further bioinformatics analysis and dual-luciferase reporter assays revealed that tsRNA-Gln-i-0095 directly targets the NFIA and TGFBR2 genes, suppressing their expression. NFIA and TGFBR2 play key roles in Müller cell activation and inflammatory responses, indicating that tsRNA-Gln-i-0095 influences the progression of retinal I/R injury by regulating these genes.

5. Role of tsRNA-Gln-i-0095 in Retinal Structure and Function

Through H&E staining and electrophysiological assessments, the research team found that overexpression of tsRNA-Gln-i-0095 exacerbated retinal structural damage and functional impairment caused by I/R injury, while its inhibition partially restored retinal thickness and visual function.

Conclusions and Significance

This study is the first to reveal the important role of tsRNA-Gln-i-0095 in retinal I/R injury. tsRNA-Gln-i-0095 regulates NFIA and TGFBR2 genes, influencing Müller cell activation and inflammatory responses, thereby affecting RGC survival and retinal function. This discovery provides a new potential therapeutic target for retinal I/R injury, with significant scientific and clinical value.

Research Highlights

1. Novel Regulatory Mechanism: This study is the first to reveal that tsRNA-Gln-i-0095 regulates NFIA and TGFBR2 genes through a miRNA-like mechanism, influencing the progression of retinal I/R injury.
2. Multi-level Experimental Validation: The study comprehensively validated the role of tsRNA-Gln-i-0095 in retinal I/R injury through in vivo and in vitro experiments, yielding highly credible results.
3. Potential Therapeutic Target: Inhibition of tsRNA-Gln-i-0095 significantly alleviates retinal I/R injury, providing a theoretical basis for developing new treatment strategies.

Other Valuable Information

This study also provides detailed information on the dynamic expression changes and subcellular localization of tsRNA-Gln-i-0095 in retinal I/R injury, offering important references for further research on the role of tsRNAs in ocular diseases.

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Through this study, we have gained a deeper understanding of the regulatory mechanisms of tsRNA-Gln-i-0095 in retinal I/R injury and provided a significant theoretical foundation for developing new treatment strategies. In the future, therapeutic approaches based on tsRNA-Gln-i-0095 may become a new direction for treating retinal I/R injury.