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Int. J. Mol. Sci. 2017, 18(3), 533; doi:10.3390/ijms18030533

Effects of Ranibizumab and Aflibercept on Human Müller Cells and Photoreceptors under Stress Conditions

Macula Research Group, Clinical Ophthalmology and Eye Health, Save Sight Institute, The University of Sydney, Sydney, NSW 2000, Australia
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Author to whom correspondence should be addressed.
Academic Editors: Claudio Bucolo and Chiara Maria Eandi
Received: 3 January 2017 / Revised: 16 February 2017 / Accepted: 24 February 2017 / Published: 1 March 2017
(This article belongs to the Special Issue Retinal Diseases: Bridging Basic and Clinical Research)
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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. View Full-Text
Keywords: vascular endothelial growth factor; aflibercept; ranibizumab; Müller cells; photoreceptors; neurotrophic factors; heat shock proteins; redox proteins; interphotoreceptor retinoid-binding protein vascular endothelial growth factor; aflibercept; ranibizumab; Müller cells; photoreceptors; neurotrophic factors; heat shock proteins; redox proteins; interphotoreceptor retinoid-binding protein
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MDPI and ACS Style

Shen, W.; Yau, B.; Lee, S.-R.; Zhu, L.; Yam, M.; Gillies, M.C. Effects of Ranibizumab and Aflibercept on Human Müller Cells and Photoreceptors under Stress Conditions. Int. J. Mol. Sci. 2017, 18, 533.

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