Epigenetic Modifications in Hyperhomocysteinemia: Potential Role in Diabetic Retinopathy and Age-related Macular Degeneration

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Mar 22

PMID 29560091

Citations 29

Authors

Khaled Elmasry

Riyaz Mohamed

Isha Sharma

Nehal M Elsherbiny

Yutao Liu

Mohamed Al-Shabrawey

Amany Tawfik

Affiliations

Soon will be listed here.

Abstract

To study Hyperhomocysteinemia (HHcy)-induced epigenetic modifications as potential mechanisms of blood retinal barrier (BRB) dysfunction, retinas isolated from three- week-old mice with elevated level of Homocysteine (Hcy) due to lack of the enzyme cystathionine β-synthase ( , and ), human retinal endothelial cells (HRECs), and human retinal pigmented epithelial cells (ARPE-19) treated with or without Hcy were evaluated for (1) histone deacetylases (HDAC), (2) DNA methylation (DNMT), and (3) miRNA analysis. Differentially expressed miRNAs in mice with HHcy were further compared with miRNA analysis of diabetic mice retinas (STZ) and miRNAs within the exosomes released from Hcy-treated RPEs. Differentially expressed miRNAs were further evaluated for predicted target genes and associated pathways using Ingenuity Pathway Analysis. HHcy significantly increased HDAC and DNMT activity in HRECs, ARPE-19, and mice retinas, whereas inhibition of HDAC and DNMT decreased Hcy-induced BRB dysfunction. MiRNA profiling detected 127 miRNAs in and 39 miRNAs in mice retinas, which were significantly differentially expressed compared to . MiRNA pathway analysis showed their involvement in HDAC and DNMT activation, endoplasmic reticulum (ER), and oxidative stresses, inflammation, hypoxia, and angiogenesis pathways. Hcy-induced epigenetic modifications may be involved in retinopathies associated with HHcy, such as age-related macular degeneration and diabetic retinopathy.

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