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Effects of VEGF inhibitors on human retinal pigment epithelium under high glucose and hypoxia
Author(s) -
Bahrami Bobak,
Shen Weiyong,
Zhu Ling,
Zhang Ting,
Chang Andrew,
Gillies Mark C.
Publication year - 2019
Publication title -
clinical and experimental ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.3
H-Index - 74
eISSN - 1442-9071
pISSN - 1442-6404
DOI - 10.1111/ceo.13579
Subject(s) - pedf , retinal pigment epithelium , vascular endothelial growth factor , neurotrophic factors , medicine , hypoxia (environmental) , endocrinology , retinal , downregulation and upregulation , viability assay , glial cell line derived neurotrophic factor , vascular endothelial growth factor a , angiogenesis , cell culture , biology , chemistry , receptor , ophthalmology , biochemistry , genetics , organic chemistry , oxygen , gene , vegf receptors
Background Retinal pigment epithelium (RPE) is known to secrete factors important for retinal homeostasis. How this secretome changes in diabetic eyes treated with anti‐vascular endothelial growth factor (VEGF) inhibitors is unclear. Methods Diabetic conditions were simulated in vitro using ARPE‐19 cell‐line culture, with high glucose (25 mM) culture media, and hypoxia was chemically induced using cobalt chloride. Stress was assessed using cell viability assays as well as Western blots and enzyme‐linked immunosorbent assay (ELISA) for production of HIF‐1a and VEGF‐A. Production of neurotrophic factors was quantified once conditions were established using ELISA under stress with and without the addition of VEGF inhibitors. Changes were analysed with one‐way ANOVA. Results Hypoxia downregulated pigment epithelium‐derived factor (PEDF) expression. The addition of bevacizumab, ranibizumab and aflibercept in normoxic conditions all led to a significant downregulation of PEDF. Glucose concentration had no effect on secretion of PEDF. Brain‐derived neurotrophic factor (BDNF) secretion was downregulated in high glucose and was upregulated in hypoxia. Placental growth factor (PlGF) secretion by ARPE‐19 was undetectable by ELISA. Conclusions We found that hypoxia, high glucose or VEGF inhibitors affected secretion of neurotrophic factors. This variation under different conditions may influence neuron and photoreceptor survival in the diabetic state and VEGF inhibitor treated eyes.