title: Effects of Ranibizumab and Aflibercept on Human Müller Cells and Photoreceptors under Stress Conditions.
abstract: Anti-vascular endothelial growth factor (VEGF) therapy has revolutionized the treatment of retinal vascular diseases. However, constitutive VEGF also acts as a trophic factor on retinal nonvascular cells. We have studied the effects of aflibercept and ranibizumab on human Müller cells and photoreceptors exposed to starvation media containing various concentrations of glucose, with or without CoCl2-induced hypoxia. Cell survival was assessed by calcein-AM cell viability assays. Expression of heat shock proteins (Hsp) and redox proteins thioredoxin 1 and 2 (TRX1, TRX2) was studied by Western blots. The production of neurotrophic factors in Müller cells and interphotoreceptor retinoid-binding protein (IRBP) in photoreceptors was measured by enzymelinked immunosorbent assays. Aflibercept and ranibizumab did not affect the viability of both types of cells. Neither aflibercept nor ranibizumab affected the production of neurotrophic factors or expression of Hsp60 and Hsp90 in Müller cells. However, aflibercept but not ranibizumab affected the expression of Hsp60, Hsp9, TRX1 and TRX2 in photoreceptors. Aflibercept and ranibizumab both inhibited the production of IRBP in photoreceptors, aflibercept more so than ranibizumab. Our data indicates that the potential influence of aflibercept and ranibizumab on photoreceptors should be specifically monitored in clinical studies.
authors.affiliation: Macula Research Group, Clinical Ophthalmology and Eye Health, Save Sight Institute, The University of Sydney, Sydney, NSW 2000, Australia. weiyong.shen@sydney.edu.au.
authors.forename: Weiyong
authors.initials: W
authors.lastname: Shen
authors.affiliation: Macula Research Group, Clinical Ophthalmology and Eye Health, Save Sight Institute, The University of Sydney, Sydney, NSW 2000, Australia. belinda.yau@sydney.edu.au.
authors.forename: Belinda
authors.initials: B
authors.lastname: Yau
authors.affiliation: Macula Research Group, Clinical Ophthalmology and Eye Health, Save Sight Institute, The University of Sydney, Sydney, NSW 2000, Australia. sora.lee@sydney.edu.au.
authors.forename: So-Ra
authors.initials: SR
authors.lastname: Lee
authors.affiliation: Macula Research Group, Clinical Ophthalmology and Eye Health, Save Sight Institute, The University of Sydney, Sydney, NSW 2000, Australia. ling.zhu@sydney.edu.au.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Macula Research Group, Clinical Ophthalmology and Eye Health, Save Sight Institute, The University of Sydney, Sydney, NSW 2000, Australia. michelle.yam@sydney.edu.au.
authors.forename: Michelle
authors.initials: M
authors.lastname: Yam
authors.affiliation: Macula Research Group, Clinical Ophthalmology and Eye Health, Save Sight Institute, The University of Sydney, Sydney, NSW 2000, Australia. mark.gillies@sydney.edu.au.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Gillies
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D063928:Ependymoglial Cells / Q000187:drug effects* / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D010786:Photoreceptor Cells / Q000187:drug effects* / Q000378:metabolism*; D000069579:Ranibizumab / Q000494:pharmacology*; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D012177:Retinol-Binding Proteins / Q000378:metabolism; D013312:Stress, Physiological; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D020533:Angiogenesis Inhibitors; D005136:Eye Proteins; D005947:Glucose; D006360:Heat-Shock Proteins; D009414:Nerve Growth Factors; D000069579:Ranibizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins; D012177:Retinol-Binding Proteins; D013879:Thioredoxins; D000099214:Retinol-Binding Proteins, Interstitial; C533178:aflibercept
keywords: Müller cells; aflibercept; heat shock proteins; interphotoreceptor retinoid-binding protein; neurotrophic factors; photoreceptors; ranibizumab; redox proteins; vascular endothelial growth factor