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Mohamed Mohamed, M. Tarek Moustafa, Shari R. Atilano, Abdul Sami Memon, Mohamed Riazi, Sean W Tsao, Cristina M Kenney, Baruch D Kuppermann; Effects of anti-angiogenic drugs on expression patterns of genes involved in different AMD pathogenetic pathways. Invest. Ophthalmol. Vis. Sci. 2017;58(8):204. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Age-related macular degeneration (AMD) is a highly heritable neurodegenerative disease with at least 19 identified risk loci to date. This study examines effects of anti-VEGF drugs on the expression of genes involved in different AMD pathogenetic pathways in immortalized human RPE cells (ARPE-19) in vitro.
ARPE-19 cells were treated for 24 h with ranibizumab, bevacizumab, or aflibercept in 1X and 2X concentrations of the clinical intravitreal dose. Untreated cells were used as controls. RNA was isolated and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed in triplicate using primers for angiogenesis (VEGFA and HIF1A), apoptosis (BAX and BCL2L13), inflammation (IL18 and IL1B) and oxidative stress (GPX3 and SOD2). ΔΔCt (differences in cycle thresholds) was obtained and folds calculated using the formula 2^ΔΔCt. Unpaired t test was used for statistical analysis.
Aflibercept-treated cells significantly overexpressed GPX3 and IL1B at 1X concentration, and SOD2, BAX, GPX3, and BCL2L13 at 2X concentration compared to untreated cultures. Ranibizumab-treated cells significantly overexpressed SOD2, BAX, GPX3, and BCL2L13 at 1X concentration, and HIF1A, SOD2, BAX, GPX3, and BCL2L13 at 2X concentration. Bevacizumab-treated cells significantly overexpressed VEGFA, HIF1A, SOD2, BAX, GPX3, and BCL2L13 at 1X concentration, and VEGFA, SOD2, BAX, GPX3, IL1B, and BCL2L13 (Table 1).
Our results show that anti-VEGF drugs can alter expression of angiogenesis, apoptosis and inflammation genes, which are important pathways involved in AMD pathogenesis. Our findings suggest that in addition to binding vascular endothelial growth factor (VEGF) and blocking receptor interactions for angiogenesis inhibition, these drugs have broader mechanisms of action. That may help us understand patient’s variability in response to anti-VEGF drugs.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
Table 1. Differences in gene expression after treatment with anti-VEGF drugs. Folds > 1 denote gene upregulation and folds < 1 gene downregulation compared to untreated.
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