2. Academic Validation
  3. Reln-Dab1 pathway mitigates retinal ganglion cell apoptosis in retinal ischemia-reperfusion injury

Reln-Dab1 pathway mitigates retinal ganglion cell apoptosis in retinal ischemia-reperfusion injury

  • Cell Death Dis. 2025 May 29;16(1):423. doi: 10.1038/s41419-025-07742-6.
Ning Xu # 1 2 3,  Zongyuan Li # 1 2 3,  Xiangwen Zeng # 1 2 3,  Yilin Jiang 1 2 3,  Tunan Sun 1 2 3,  Shuyu Liu 1 2 4,  Na Li 1 2 4,  Zhao Li 1 2 4,  Yifei Huang 5 6 7,  Liqiang Wang 8 9 10
Affiliations

Affiliations

  • 1 Medical School of Chinese People's Liberation Army, Beijing, China.
  • 2 Department of Ophthalmology, The Third Medical Center, General Hospital of Chinese People's Liberation Army, Beijing, China.
  • 3 State Key Laboratory of Kidney Diseases, General Hospital of Chinese People's Liberation Army, Beijing, China.
  • 4 School of Medicine, Nankai University, Tianjin, China.
  • 5 Medical School of Chinese People's Liberation Army, Beijing, China. 301yk@sina.com.
  • 6 Department of Ophthalmology, The Third Medical Center, General Hospital of Chinese People's Liberation Army, Beijing, China. 301yk@sina.com.
  • 7 State Key Laboratory of Kidney Diseases, General Hospital of Chinese People's Liberation Army, Beijing, China. 301yk@sina.com.
  • 8 Medical School of Chinese People's Liberation Army, Beijing, China. liqiangw301@163.com.
  • 9 Department of Ophthalmology, The Third Medical Center, General Hospital of Chinese People's Liberation Army, Beijing, China. liqiangw301@163.com.
  • 10 State Key Laboratory of Kidney Diseases, General Hospital of Chinese People's Liberation Army, Beijing, China. liqiangw301@163.com.
  • # Contributed equally.
PMID: 40442071 DOI: 10.1038/s41419-025-07742-6
Abstract

Ischemia-reperfusion (I/R) injury is associated with a variety of retinal diseases, resulting in loss of the number of ganglion cells (RGCs), retinal structural disorders, and retinal dysfunction. The Reelin protein is an important regulator of neuronal migration and synaptogenesis, and the Reln signaling pathway plays an essential role in regulating the targeted projection of RGC dendrites and neuronal survival, which has not been reported in retinal I/R injury. The aim of this study was to investigate the expression, role and mechanism of Reln in retinal I/R injury. By establishing Reln-CreERT2 mTmG transgenic mice, it was observed that the expression of Reln initially decreased and then increased after retinal I/R injury. After supplementing exogenous Reelin protein and adeno-associated virus (AAV)-targeted regulation of Reln in vivo, morphological and functional experiments demonstrated its effectiveness in protecting RGCs survival, maintaining morphological integrity of the retina, and inhibiting post-injury retinal dysfunction. Furthermore, Integrin β1 (Itgb1) was identified as the main receptor through which Reelin exerts neuroprotective effects while regulating retinal I/R injury repair through the Dab1-PI3K-Akt pathway. These findings provide evidence supporting Reln pathway's role in maintaining retinal homeostasis and facilitating injury repair. Moreover, these findings have significant implications for identifying new targets for preventing and treating various retinal diseases.

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