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Resveratrol prevents hypoxia-induced retinal ganglion cell death related with ErbB2
Authors:Hyemin Seong  Joo Yeon Jeong  Jinhyun Ryu  Juyeong Park  Yong-Seop Han  Hyun-Kyung Cho  Seong Jae Kim  Jong Moon Park  Sang Soo Kang and Seong Wook Seo
Institution:Department of Ophthalmology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Republic of Korea,Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Republic of Korea,Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Republic of Korea,Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Republic of Korea,Department of Ophthalmology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Republic of Korea,Department of Ophthalmology, Gyeongsang National University Changwon Hospital, Gyeongsang National University, College of Medicine, Changwon 51472, Republic of Korea,Department of Ophthalmology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Republic of Korea,Department of Ophthalmology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Republic of Korea,Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Republic of Korea and Department of Ophthalmology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Republic of Korea
Abstract: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.
Keywords:ischemia/reperfusion injury  hypoxia  retinal ganglion cell  resveratrol  ErbB2
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