Anti-VEGF Drugs Influence Epigenetic Regulation and AMD-Specific Molecular Markers in ARPE-19 Cells

Author:

Hamid Mohamed A.ORCID,Moustafa M. TarekORCID,Nashine Sonali,Costa Rodrigo DonatoORCID,Schneider Kevin,Atilano Shari R.ORCID,Kuppermann Baruch D.,Kenney M. Cristina

Abstract

Our study assesses the effects of anti-VEGF (Vascular Endothelial Growth Factor) drugs and Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC) activity, on cultured ARPE-19 (Adult Retinal Pigment Epithelial-19) cells that are immortalized human retinal pigment epithelial cells. ARPE-19 cells were treated with the following anti-VEGF drugs: aflibercept, ranibizumab, or bevacizumab at 1× and 2× concentrations of the clinical intravitreal dose (12.5 μL/mL and 25 μL/mL, respectively) and analyzed for transcription profiles of genes associated with the pathogenesis age-related macular degeneration (AMD). HDAC activity was measured using the Fluorometric Histone Deacetylase assay. TSA downregulated HIF-1α and IL-1β genes, and upregulated BCL2L13, CASPASE-9, and IL-18 genes. TSA alone or bevacizumab plus TSA showed a significant reduction of HDAC activity compared to untreated ARPE-19 cells. Bevacizumab alone did not significantly alter HDAC activity, but increased gene expression of SOD2, BCL2L13, CASPASE-3, and IL-18 and caused downregulation of HIF-1α and IL-18. Combination of bevacizumab plus TSA increased gene expression of SOD2, HIF-1α, GPX3A, BCL2L13, and CASPASE-3, and reduced CASPASE-9 and IL-β. In conclusion, we demonstrated that anti-VEGF drugs can: (1) alter expression of genes involved in oxidative stress (GPX3A and SOD2), inflammation (IL-18 and IL-1β) and apoptosis (BCL2L13, CASPASE-3, and CASPASE-9), and (2) TSA-induced deacetylation altered transcription for angiogenesis (HIF-1α), apoptosis, and inflammation genes.

Publisher

MDPI AG

Subject

General Medicine

Cited by 12 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3