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Updated: Sep 29, 2025
A Mouse Model of Retinal Ischemia-Reperfusion Injury Through Elevation of Intraocular Pressure
Published on: July 14, 2016
Resveratrol prevents hypoxia-induced retinal ganglion cell death related with ErbB2
Hyemin Seong1, Joo Yeon Jeong2, Jinhyun Ryu2
1Department of Ophthalmology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Republic of Korea.
Aim:
To confirm the changes in proteins related with hypoxia-induced retinal cell death and to assess the effects of resveratrol (Res).
Methods:
The therapeutic effect of Res was verified using an ischemic/reperfusion (I/R) model in vivo and a hypoxia modelin retinal ganglion cells (RGCs) in vitro. Death of RGCs were confirmed by TUNEL assay. Protein expression was confirmed by Western blotting and immunohistochemistry. In addition, flow cytometric analysis was used to confirm the response in the cell unit to obtain more accurate data.
Results:
ErbB2 expression and apoptosis in the ganglion cell layer (GCL) increased after I/R injury. Treatment of Res rescued I/R-induced ganglion cell death, downregulated apoptosis and ErbB2 protein expression in the retina. In subsequent in vitro models, Res affects apoptosis by regulating the phosphorylation and expression of mouse double minute 2 homolog (MDM2), along with those of ErbB2. These results suggest that Res reverses GCL-specific apoptosis via downregulation of ErbB2 in ischemic injury.
Conclusion:
In light of Res favorable properties, it should be evaluated in the treatment of RGC death and related retinal disease characterized by ErbB2 and MDM2 expression. Therefore, Res is appropriate therapeutic agent for treating ischemic injury-related eye diseases by targeting the expression of ErbB2 and MDM2.
Insights
Resveratrol (Res) protects retinal ganglion cells (RGCs) from ischemic injury by downregulating ErbB2 and MDM2 proteins, offering a potential treatment for related eye diseases.
Area of Science:
- Ophthalmology
- Neuroscience
- Molecular Biology
Background:
- Hypoxia-induced retinal cell death is a significant cause of vision loss.
- ErbB2 and MDM2 proteins are implicated in retinal cell apoptosis during ischemic injury.
Purpose of the Study:
- To investigate the role of ErbB2 and MDM2 in hypoxia-induced retinal cell death.
- To evaluate the therapeutic potential of resveratrol (Res) in mitigating these effects.
Main Methods:
- Utilized an *in vivo* ischemic/reperfusion (I/R) model and an *in vitro* hypoxia model of retinal ganglion cells (RGCs).
- Assessed RGC death via TUNEL assay, protein expression through Western blotting and immunohistochemistry, and cellular responses using flow cytometry.
Main Results:
- I/R injury increased ErbB2 expression and apoptosis in the retinal ganglion cell layer (GCL).
- Resveratrol treatment reduced RGC death, apoptosis, and ErbB2 expression.
- Resveratrol modulated MDM2 phosphorylation and expression, alongside ErbB2, in *in vitro* models, reversing GCL-specific apoptosis.
Conclusions:
- Resveratrol demonstrates therapeutic potential for ischemic injury-related eye diseases.
- Targeting ErbB2 and MDM2 expression with resveratrol may be a viable treatment strategy for retinal conditions involving RGC death.
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