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

Sonali Nashine1, Anthony B Nesburn2, Baruch D Kuppermann1

  • 1Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA, USA.

Experimental Eye Research
|June 22, 2019
PubMed

Insights

Mitochondrial dysfunction in Age-related Macular Degeneration (AMD) impacts epigenetic gene regulation in retinal cells. Targeting these epigenetic changes offers potential new therapies for AMD.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Epigenetics

Background:

  • Mitochondrial damage and epigenetic alterations are key factors in Age-related Macular Degeneration (AMD) pathogenesis.
  • Retinal Pigment Epithelial (RPE) cells are crucial for retinal health and are affected in AMD.

Purpose of the Study:

  • To investigate how mitochondria from AMD patients influence epigenetic regulation in human RPE cells.
  • To explore the role of mitochondria-nucleus interactions in AMD development.

Main Methods:

  • Created human RPE cybrid cell lines with identical nuclei but different mitochondrial origins (AMD patients vs. normal subjects).
  • Analyzed gene expression of methylation- and acetylation-related genes.
  • Utilized demethylation (5-Aza-2'-deoxycytidine) and HDAC inhibition (Trichostatin A) to assess effects on gene expression.

Main Results:

  • AMD cybrids showed altered expression of multiple methylation- and acetylation-related genes compared to normal cybrids.
  • Demethylation treatment decreased VEGF-A gene expression in AMD cells.
  • HDAC inhibition affected protein levels of key genes including VEGF-A, HIF1α, NFκB, and CFH in AMD cells.

Conclusions:

  • Retrograde signaling from mitochondria to the nucleus alters the epigenetic status of RPE cells in AMD.
  • These findings highlight mitochondria-nucleus communication as a potential therapeutic target for Age-related Macular Degeneration.
Keywords:
AMDAMD mitochondriaAcetylationAge-related macular degenerationEpigeneticsMethylation

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