Age-related macular degeneration (AMD) mitochondria modulate epigenetic mechanisms in retinal pigment epithelial cells.

Abstract:

:Mitochondrial damage and epigenetic modifications have been implicated in the pathogenesis of Age-related Macular Degeneration (AMD). This study was designed to investigate the effects of AMD/normal mitochondria on epigenetic regulation in human transmitochondrial retinal pigment epithelial (RPE) cells in vitro. Human RPE cybrid cell lines were created by fusing mitochondria-deficient (Rho0) ARPE-19 cells with platelets obtained from either AMD patients (AMD cybrids) or normal subjects (normal cybrids). Therefore, all cybrids had identical nuclei (derived from ARPE-19 cells) but mitochondria derived from either AMD patients or age-matched normal subjects. AMD cybrids demonstrated increased RNA/protein levels for five methylation-related and four acetylation-related genes, along with lower levels of two methylation and three acetylation genes compared to normal cybrids. Demethylation using 5-Aza-2'-deoxycytidine (DAC) led to decreased expression of VEGF-A gene in AMD cells. Trichostatin A (TSA), an HDAC inhibitor, also influenced protein levels of VEGF-A, HIF1α, NFκB, and CFH in AMD cells. Our findings suggest that retrograde signaling leads to mitochondria-nucleus interactions that influence the epigenetic status of the RPE cells and this may help in the identification of future potential therapeutic targets for AMD.

journal_name

Exp Eye Res

authors

Nashine S,Nesburn AB,Kuppermann BD,Kenney MC

doi

10.1016/j.exer.2019.107701

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

107701

eissn

0014-4835

issn

1096-0007

pii

S0014-4835(18)30773-5

journal_volume

189

pub_type

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