2. Academic Validation
  3. Geranylgeranylacetone-induced heat shock protein70 expression reduces retinal ischemia-reperfusion injury through PI3K/AKT/mTOR signaling

Geranylgeranylacetone-induced heat shock protein70 expression reduces retinal ischemia-reperfusion injury through PI3K/AKT/mTOR signaling

  • Exp Eye Res. 2023 Feb 15;109416. doi: 10.1016/j.exer.2023.109416.
Lirong Zhang 1,  Kaige Xue 1,  Ping Fan 2,  Chunyan Chen 1,  Jiaheng Hu 1,  Juan Huang 1,  Weitian Lu 1,  Jin Xu 1,  Shiye Xu 1,  Jianhua Ran 1,  Shujuan Zhu 1,  Gan Shengwei 3
Affiliations

Affiliations

  • 1 Institute of Neurosciences, Basic Medicine College of Chongqing Medical University, Chongqing, China.
  • 2 Department of Gynecology and Obstetrics of the Fifth People's Hospital of Chongqing, Chongqing, China.
  • 3 Institute of Neurosciences, Basic Medicine College of Chongqing Medical University, Chongqing, China. Electronic address: 100364@cqmu.edu.cn.
PMID: 36801237 DOI: 10.1016/j.exer.2023.109416
Abstract

Retinal ischemia-reperfusion (I/R) injury is a common pathophysiological stress state connected to various diseases, including acute glaucoma, retinal vascular obstruction, and diabetic retinopathy. Recent studies have suggested that geranylgeranylacetone (GGA) could increase heat shock protein70 (HSP70) level and reduce retinal ganglion cells (RGCs) Apoptosis in a rat retinal I/R model. However, the underlying mechanism remains unclear. Moreover, the injury caused by retinal I/R includes not only Apoptosis but also Autophagy and gliosis, and the effects of GGA on Autophagy and gliosis have not been reported. Our study established a retinal I/R model by anterior chamber perfusion pressuring to 110 mmHg for 60 min, followed by 4 h of reperfusion. The levels of HSP70, apoptosis-related proteins, GFAP, LC3-II, and PI3K/Akt/mTOR signaling proteins were determined by western blotting and qPCR after treatment with GGA, HSP70 Inhibitor quercetin (Q), PI3K Inhibitor LY294002, and mTOR Inhibitor rapamycin. In addition, Apoptosis was evaluated by TUNEL staining, and HSP70 was detected by immunofluorescence. Our results demonstrated that GGA-induced HSP70 expression significantly reduced gliosis, autophagosome accumulation, and Apoptosis in retinal I/R injury, indicating that GGA had a protective effect on retinal I/R injury. Moreover, the protective effect of GGA mechanistically relies on activating PI3K/Akt/mTOR signaling. In conclusion, GGA-induced HSP70 overexpression has a protective effect on retinal I/R injury by activating PI3K/Akt/mTOR signaling.

Keywords

Apoptosis; Autophagy; Gliosis; Heat shock protein 70; Retinal ischemia-reperfusion injury.

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