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Weiyong Shen, Belinda Yau, SoRa Lee, Ling Zhu, Michelle Yam, Mark C Gillies; Effects of ranibizumab and aflibercept on human Müller cells and photoreceptors under stress. Invest. Ophthalmol. Vis. Sci. 2017;58(8):877.
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© ARVO (1962-2015); The Authors (2016-present)
The advent of anti-vascular endothelial growth factor (VEGF) agents has revolutionized the treatment of retinal vascular diseases. A growing body of evidence indicates that constitutive VEGF also acts as a trophic factor on non-vascular cells. The aim of this study was to evaluate the potential adverse effects of ranibizumab and aflibercept on human Müller cells and photoreceptors under stress.
We studied the effects of aflibercept and ranibizumab on human Müller cells and photoreceptors exposed to starvation media containing various concentrations of glucose, with and without CoCl2-induced hypoxia. Cell survival was assessed by calcein-AM cell viability assays. Expression of heat shock proteins (Hsp) was studied by Western blots. The production of neurotrophic factors including neurotrophin 3 (NT3), brain derived neurotrophic factor (BDNF) and pigment epithelium derived factor (PEDF) in Müller cells and interphotoreceptor retinoid-binding protein (IRBP) in photoreceptors was measured by enzyme-linked immunosorbent assays.
Aflibercept and ranibizumab did not affect the viability of either human Müller cells or photoreceptors under the conditions of stress (high glucose, hypoxia) we tested. Neither aflibercept nor ranibizumab affected the production of neurotrophic factors or expression of Hsp60 and Hsp90 in Müller cells. In photoreceptors, however, aflibercept but not ranibizumab affected the expression of Hsp60 and Hsp90. Aflibercept and ranibizumab both inhibited the production of IRBP by photoreceptors, aflibercept more so than ranibizumab.
Our data indicate that aflibercept and ranibizumab did not have adverse effects on Müller cells but their potential effect on photoreceptors warrants closer observation in clinical studies.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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