Title
Effects of antiangiogenic drugs on expression patterns of epigenetic pathway genes
Date Issued
01 October 2018
Access level
metadata only access
Resource Type
conference paper
Author(s)
University of California
Publisher(s)
Slack Incorporated
Abstract
BACKGROUND AND OBJECTIVE: To investigate the effects of antiangiogenic drugs on the transcription profile of acetylation genes in immortalized human retinal pigment epithelium cells (ARPE-19) in vitro. MATERIALS AND METHODS: This in vitro study evaluated the effect of antiangiogenic drugs on the expression of histone acetylation genes on immortalized ARPE-19 cell cultures. ARPE-19 cells were cultured, plated, and treated for 24 hours with aflibercept (Eylea; Regeneron, Tarrytown, NY), ranibizumab (Lucentis; Genentech, South San Francisco, CA), or bevacizumab (Avastin; Genentech, South San Francisco, CA) at one (1x) or two times (2x) the concentrations of the clinical intravitreal dose. Untreated cells were used as controls. RNA was isolated, and real-time quantitative reverse transcription polymerase chain reaction analysis was performed on individual samples to quantify expression levels of genes associated with epigenetic acetylation pathways: histone acetyltransferase 1 (HAT1) and histone deacetylases 1, 6, and 11 (HDAC1, HDAC6, and HDAC11). Differences in cycle thresholds (ΔΔCts) were obtained, and folds were calculated using the formula 2^ΔΔCt. Main outcome measures were expression levels of candidate genes in treated versus untreated samples. RESULTS: Compared with untreated cells, 1x ranibizumab-treated cells expressed higher levels of HDAC6, and 2x ranibizumab-treated cells expressed higher HDAC11 levels. Bevacizumab-treated (1x) cells had significant change in HDAC1, HDAC6, and HDAC11. In cultures treated with 2x bevacizumab, only HDAC11 expression levels were significantly affected compared with controls. Aflibercept-treated (1x) cells had changes in expression of HDAC1, HDAC6, and HDAC11. At 2x concentration, only HDAC11 was significantly changed. CONCLUSION: Our results show that antiangiogenic drugs can affect the transcription profile of genes regulating the histone acetylation status in ARPE-19 cells in vitro. This finding may have an implication in differential patient response to anti-vascular endothelial growth factor therapy by means of possible interactions between treatment and patient's epigenomic profile.
Start page
S29
End page
S33
Volume
49
Issue
10
Language
English
OCDE Knowledge area
FarmacologÃa, Farmacia
OftalmologÃa
Scopus EID
2-s2.0-85055075067
PubMed ID
ISSN of the container
23258160
Conference
Ophthalmic Surgery Lasers and Imaging Retina
Sponsor(s)
Originally submitted June 28, 2018. Revisions received August 3, 2018. Accepted August 5, 2018. Presented at the 2017 Retina Research Scholar Honoree Program Symposium in New Orleans. This study was supported by Discovery Eye Foundation, Polly and Michael Smith Foundation, Iris and B. Gerald Cantor Foundation, Beckman Initiative for Macular Research, Max Factor Family Foundation, and Guen-ther Foundation. This study was also supported in part by an unrestricted grant from Research to Prevent Blindness, Inc. The authors acknowledge the support of the Institute for Clinical and Translational Science at University of California, Irvine. Dr. Kuppermann is a consultant to Aerpio, Alcon, Alimera, Allegro, Allergan, Catalyst, Cell Care, Dose, Eyedaptic, Genentech, Glaukos, Glaxo-SmithKline, jCyte, Neurotech, Novagali, Novartis, Ophthotech, Pfizer, Re-generon, Santen, SciFluor, Second Sight, Teva, and ThromboGenics and has received reserach funding from Alcon, Alimera, Allegro, Allergan, Apellis, Genentech, Glaukos, GlaxoSmithKline, Ionis, jCyte, Ophthotech, Regeneron and ThromboGenics. The remaining authors report no relevant financial disclosures. Address correspondence to Mohamed A. Hamid, MD, 850 Health Sciences Rd., Irvine, CA 92697; email: mahamid@uci.edu. doi: 10.3928/23258160-20180814-05
This study was supported by Discovery Eye Foundation, Polly and Michael Smith Foundation, Iris and B. Gerald Cantor Foundation, Beckman Initiative for Macular Research, Max Factor Family Foundation, and Guen-ther Foundation. This study was also supported in part by an unrestricted grant from Research to Prevent Blindness, Inc. The authors acknowledge the support of the Institute for Clinical and Translational Science at University of California, Irvine.
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