AUTHOR=Guo Ju , Zhou Pengyi , Liu Zhenhui , Dai Fangfang , Pan Meng , An Guangqi , Han Jinfeng , Du Liping , Jin Xuemin 

TITLE=The Aflibercept-Induced MicroRNA Profile in the Vitreous of Proliferative Diabetic Retinopathy Patients Detected by Next-Generation Sequencing

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.781276

DOI=10.3389/fphar.2021.781276

ISSN=1663-9812

ABSTRACT=Abstract
Purpose 
Vascular endothelial growth factor-A (VEGF-A) is an important pathogenic factor in proliferative diabetic retinopathy (PDR), aflibercept (Eylea) is one of the widely used anti-VEGF agents. This study investigated the microRNA(miRNA) profiles in the vitreous of 5 idiopathic macular hole patients (non-diabetic controls), 5 untreated PDR patients (no-treatment group) and 5 PDR patients treated with intravitreal aflibercept injection (treatment group). 
Methods
Next-generation sequencing was performed to determine the miRNA profiles. Deregulated miRNAs were validated with quantitative real-time Polymerase Chain Reaction (qRT-PCR ) in another cohort. The mRNAs profile data (GSE160310) of PDR patients was retrieved from the Gene Expression Omnibus (GEO) database. The function of differentially expressed miRNAs and mRNAs were annotated by bioinformatic analysis and literature study.
Results
Twenty-nine miRNAs were significantly dysregulated in the three groups, of which 19,984 target mRNAs were predicted. Hsa-miR-3184-3p, hsa-miR-24-3p and hsa-miR-197-3p were validated to be remarkably upregulated in no-treatment group vs controls, and significantly downregulated in treatment group vs no-treatment group. In the GSE160310 profile, 204 deregulated protein coding mRNAs were identified, and finally 179 overlapped mRNAs between the 19,984 target mRNAs and 204 deregulated mRNAs were included for further analysis. Function analysis provided several roles of aflibercept-induced miRNAs, promoting the alternation of drug sensitivity or resistance-related mRNAs, regulating critical mRNAs involved in angiogenesis and retinal fibrosis.
Conclusion
Hsa-miR-3184-3p, hsa-miR-24-3p and hsa-miR-197-3p were highly expressed in PDR patients, intravitreal aflibercept injection could reverse this alteration. Intravitreal aflibercept injection may involve in regulating cell sensitivity or resistance to drug, angiogenesis and retinal fibrosis.
This trial is registered on the website[  https://61.49.19.26/login] and its unique identifier is 2021-KY-0176-002.