Key immune regulators in retinal ischemia-reperfusion injury via RNA sequencing

AIM: To explore the immune cell infiltration and molecular mechanisms of retinal ischemia-reperfusion injury (RIRI) to identify potential therapeutic targets. METHODS: In the bulk RNA-seq analysis, This study performed differential gene expression analysis, weighted gene co-expression network analys...

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Main Authors: Shan He, Cui-Ying Liu, Chang-Hong Ren, Ting-Ting Meng, Heng Zhao, Xu-Xiang Zhang
Format: Article
Language:English
Published: Press of International Journal of Ophthalmology (IJO PRESS) 2025-07-01
Series:International Journal of Ophthalmology
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Online Access:http://ies.ijo.cn/en_publish/2025/7/20250706.pdf
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Summary:AIM: To explore the immune cell infiltration and molecular mechanisms of retinal ischemia-reperfusion injury (RIRI) to identify potential therapeutic targets. METHODS: In the bulk RNA-seq analysis, This study performed differential gene expression analysis, weighted gene co-expression network analysis, and protein-protein interaction network analysis to identify hub genes. QuanTIseq was used to determine the composition of infiltrating immune cells. Following the identification of hub genes, single-cell RNA-seq analysis was employed to pinpoint the specific immune cell types expressing these hub genes. Cell-cell communication analysis to explore signaling pathways and interactions between immune cells was further performed. Finally, the expression of these key immune regulators in vivo using quantitative real-time polymerase chain reaction (qRT-PCR) was validated. RESULTS: Bulk RNA-seq analysis identified Stat2, Irf7, Irgm1, Igtp, Parp9, Irgm2, Nlrc5, and Tap1 as hub genes, with strong correlations to immune cell infiltration. Single-cell RNA-seq analysis further revealed six immune cell clusters, showing Irf7 predominantly in microglia and Tap1 in dendritic cells (DCs). And cell-cell communication analysis showed that microglia and DCs play central roles in coordinating immune activity. qRT-PCR validated the upregulation of these genes. CONCLUSION: In the acute phase of RIRI, Irf7 and Tap1 may be the potential therapeutic targets to reduce inflammation and promote neurological function recovery.
ISSN:2222-3959
2227-4898