Effects of Ranibizumab and Aflibercept on Human Müller Cells and Photoreceptors underStress Conditions

International Journal of Molecular Sciences

Ling Zhu¹  Belinda Yau¹  So-Ra Lee¹  Michelle Yam¹  Weiyong Shen¹  Mark C. Gillies¹ 

[1] Macula Research Group, Clinical Ophthalmology and Eye Health, Save Sight Institute, The University of Sydney, Sydney, NSW 2000, Australia;

关键词: vascular endothelial growth factor;    aflibercept;    ranibizumab;    Müller cells;    photoreceptors;    neurotrophic factors;    heat shock proteins;    redox proteins;    interphotoreceptor retinoid-binding protein;   

DOI  :  10.3390/ijms18030533

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown