title: Estrogen prevents high-glucose-induced damage of retinal ganglion cells via mitochondrial pathway.
abstract: BACKGROUND
  Diabetic retinopathy (DR) is a leading cause of acquired blindness in adults. Previous research has shown that the apoptosis of retinal ganglion cells(RGCs) plays an important role in the initiation and development of diabetic retinopathy. The positive effect of estrogen on the nervous system is currently attracting increasing attention. In this study, we investigated whether17β-estradiolum (E2) has protective effects on RGCs in a high-glucose environment.
  
  
  METHODS
  The cell survival rates were measured by Cell Counting Kit-8, the apoptosis was detected by flow cytometry, the intracellular reactive oxygen species (ROS) levels were examined by immunofluorescence method, and the intracellular mitochondrial membrane potential was examined by confocal microscopy. The expression levels of cytochrome C, Bcl-2, and Bax were analyzed by Western blot method. The effect of estrogen receptor blocker tamoxifen on the RGCs was also evaluated.
  
  
  RESULTS
  It was found that E2 stabilizes the mitochondrial membrane potential, reduces intracellular ROS levels, up-regulates Bcl-2 expression, inhibits Bax expression, decreases the generation of cytochrome C, and finally reduces the apoptosis of RGC-5 cells in a high-glucose environment. These protective functions could be attributed to E2 receptors, which make E2 a prospective patent application candidate in the treatment of DR. Furthermore, when cells were pre-cultured with tamoxifen, we found that tamoxifen inhibited the shielding effects of E2.
  
  
  CONCLUSIONS
  E2 has a broad application prospect in the treatment of DR.
authors.affiliation: Department of Endocrinology, The First Clinical Hospital of Harbin Medical University, No. 23 Youzheng Street, NanGang District, Harbin, Heilongjiang Province, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Hao
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Wenjian
authors.initials: W
authors.lastname: Lin
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.forename: Ning
authors.initials: N
authors.lastname: Shao
authors.forename: Yixin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Kuang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005434:Flow Cytometry; D005947:Glucose / Q000633:toxicity*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013629:Tamoxifen / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D004965:Estrogen Antagonists; D004967:Estrogens; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D013629:Tamoxifen; D004958:Estradiol; D045304:Cytochromes c; D005947:Glucose