Seong Hyemin, Jeong Joo Yeon, Ryu Jinhyun, Park Juyeong, Han Yong-Seop, Cho Hyun-Kyung, Kim Seong Jae, Park Jong Moon, Kang Sang Soo, Seo Seong Wook
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.
Int J Ophthalmol. 2022 Mar 18;15(3):394-400. doi: 10.18240/ijo.2022.03.04. eCollection 2022.
To confirm the changes in proteins related with hypoxia-induced retinal cell death and to assess the effects of resveratrol (Res).
The therapeutic effect of Res was verified using an ischemic/reperfusion (I/R) model and a hypoxia modelin retinal ganglion cells (RGCs) . 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.
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 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 downregulation of ErbB2 in ischemic injury.
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.
确认与缺氧诱导的视网膜细胞死亡相关的蛋白质变化,并评估白藜芦醇(Res)的作用。
使用缺血/再灌注(I/R)模型和视网膜神经节细胞(RGCs)缺氧模型验证Res的治疗效果。通过TUNEL检测确认RGCs的死亡。通过蛋白质印迹法和免疫组织化学法确认蛋白质表达。此外,使用流式细胞术分析来确认细胞单位中的反应以获得更准确的数据。
I/R损伤后神经节细胞层(GCL)中的ErbB2表达和细胞凋亡增加。Res治疗可挽救I/R诱导的神经节细胞死亡,下调视网膜中的细胞凋亡和ErbB2蛋白表达。在随后的模型中,Res通过调节小鼠双微体2同源物(MDM2)以及ErbB2的磷酸化和表达来影响细胞凋亡。这些结果表明,Res可逆转缺血性损伤中GCL特异性细胞凋亡和ErbB2的下调。
鉴于Res的良好特性,应评估其在治疗以ErbB2和MDM2表达为特征的RGC死亡和相关视网膜疾病中的作用。因此,Res是通过靶向ErbB2和MDM2的表达来治疗缺血性损伤相关眼病的合适治疗剂。