title: The effects of anti-vascular endothelial growth factor agents on human retinal pigment epithelial cells under high glucose conditions.
abstract: OBJECTIVE
  To investigate the effects of high glucose levels and anti-vascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab and aflibercept) on retinal pigment epithelium (RPE) cells.
  
  
  METHODS
  ARPE-19 cells were cultured at different glucose levels (5.5 mmol/L, 25 mmol/L, and 75 mmol/L). Cell viability was evaluated by MTT assay at 3d after treatment with D-glucose. Cell migration ability was measured by wound healing assay at 3d. A cell death detection kit was used to assess apoptosis at 3 and 14d. Cell proliferation was assessed by EdU assay at 3d. The culture medium was treated with anti-VEGF agents at clinically relevant concentrations. The experiment was then repeated at a different glucose level.
  
  
  RESULTS
  The viability and migration of ARPE-19 cells were significantly decreased in the presence of 75 mmol/L as compared to 5.5 mmol/L glucose. The percentage of TUNEL-positive cells was significantly increased and the proliferative potential was decreased with 75 mmol/L compared to 5.5 mmol/L glucose. There were no significant differences in the results between 25 mmol/L and 5.5 mmol/L glucose. In the presence of 75 mmol/L glucose, the groups treated with anti-VEGF showed decreased cell viability and proliferation and increased apoptosis. However, there were no significant differences between the anti-VEGF groups.
  
  
  CONCLUSIONS
  High glucose level decreases the viability, wound healing ability, and proliferation of RPE cells, while increasing apoptosis. Furthermore, anti-VEGF agents interfered with the physiological functions of RPE cells under high-glucose conditions, accompanied by decreases in cell viability and proliferation.
authors.affiliation: Department of Ophthalmology, Soonchunhyang University, College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Jong Rok
authors.initials: JR
authors.lastname: Oh
authors.affiliation: Department of Ophthalmology, Soonchunhyang University, College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Han
authors.affiliation: Department of Ophthalmology, Soonchunhyang University, College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Soonchunhyang University, College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Ohn
authors.affiliation: Department of Ophthalmology, Soonchunhyang University, College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Tae Kwann
authors.initials: TK
authors.lastname: Park
keywords: anti-vascular endothelial growth factor; high glucose; retinal pigment epithelium