A circRNA-microRNA-Pdcd1 axis drives microglial activation and retinal ganglion cell degeneration
Abstract
Retinal ganglion cell (RGC) degeneration is the primary cause of vision loss, driven by the complicated effects of intrinsic neuronal damage and neuroinflammation. However, current single-target therapies fail to address these dual pathological challenges. CircRNAs, functioning through ceRNA networks, represent a multi-target intervention due to their stability. Here we show that, using whole‑transcriptome sequencing of optic nerve crush (ONC), we bioinformatically predicted nine candidate ceRNA networks. Among these, the network centered on circAgtpbp1 was significantly up-regulated post-injury, independent of its host gene. Mechanistically, circAgtpbp1 functions as a ceRNA by sequestering miR-3098-3p, thereby de-repressing the translation of PD-1 ( Pdcd1 ). In the ONC model, this upregulation of PD-1 protein amplifies microglial activation, creating a pathogenic non-cell-autonomous inflammatory amplification loop that drives RGC degeneration. Our findings not only uncover a novel circRNA-mediated mechanism in neurodegeneration but also identify the circAgtpbp1-miR-3098-3p-Pdcd1-microglia axis as a promising therapeutic target for neuroprotective interventions.
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BibTeX
@article{sun2026circrnamicrornapdcd1,
title = {{A circRNA-microRNA-Pdcd1 axis drives microglial activation and retinal ganglion cell degeneration}},
author = {Lanfang Sun and Xiaoyu Ke and Jingjing Yu and Jinfei Wei and Jiayi Gu and Wanchen Zhou and Yixin Cen and Jin Huang and Xiaoling Zhang and Jiaming Zhang and Shuo Zhang and Xiaojiang Liu and Yangyang Ji and Wentao Yan and Shaohui Pan and Meng Zhou and Wencan Wu},
journal = {Communications Biology},
year = {2026},
month = oct,
doi = {10.1038/s42003-026-11139-2},
url = {https://www.nature.com/articles/s42003-026-11139-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A circRNA-microRNA-Pdcd1 axis drives microglial activation and retinal ganglion cell degeneration
AU - Lanfang Sun
AU - Xiaoyu Ke
AU - Jingjing Yu
AU - Jinfei Wei
AU - Jiayi Gu
AU - Wanchen Zhou
AU - Yixin Cen
AU - Jin Huang
AU - Xiaoling Zhang
AU - Jiaming Zhang
AU - Shuo Zhang
AU - Xiaojiang Liu
AU - Yangyang Ji
AU - Wentao Yan
AU - Shaohui Pan
AU - Meng Zhou
AU - Wencan Wu
PY - 2026
DA - 2026/10/16
JO - Communications Biology
DO - 10.1038/s42003-026-11139-2
UR - https://www.nature.com/articles/s42003-026-11139-2
AB - Retinal ganglion cell (RGC) degeneration is the primary cause of vision loss, driven by the complicated effects of intrinsic neuronal damage and neuroinflammation. However, current single-target therapies fail to address these dual pathological challenges. CircRNAs, functioning through ceRNA networks, represent a multi-target intervention due to their stability. Here we show that, using whole‑transcriptome sequencing of optic nerve crush (ONC), we bioinformatically predicted nine candidate ceRNA networks. Among these, the network centered on circAgtpbp1 was significantly up-regulated post-injury, independent of its host gene. Mechanistically, circAgtpbp1 functions as a ceRNA by sequestering miR-3098-3p, thereby de-repressing the translation of PD-1 ( Pdcd1 ). In the ONC model, this upregulation of PD-1 protein amplifies microglial activation, creating a pathogenic non-cell-autonomous inflammatory amplification loop that drives RGC degeneration. Our findings not only uncover a novel circRNA-mediated mechanism in neurodegeneration but also identify the circAgtpbp1-miR-3098-3p-Pdcd1-microglia axis as a promising therapeutic target for neuroprotective interventions.
SN - 2399-3642
ER -