ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration

Area of Science:

• Genomics
• Epigenetics
• Ophthalmology

Background:

• Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults.
• The role of epigenetic modifications in AMD pathogenesis remains largely unexplored.

Purpose of the Study:

• To investigate global chromatin accessibility changes in the retina and RPE of AMD patients.
• To identify epigenetic mechanisms linking environmental risk factors to AMD.

Main Methods:

• ATAC-Seq was employed to profile chromatin accessibility in retinal and RPE samples from AMD and control individuals.
• In vitro studies exposed RPE cells to cigarette smoke to model epigenetic changes.

Main Results:

• Global chromatin accessibility decreased in RPE with early AMD and in the retina with advanced AMD.
• Differentially accessible regions (DARs) were enriched for RPE/photoreceptor transcription factor binding sites, with associated gene expression alterations.
• Cigarette smoke exposure mimicked AMD-associated chromatin changes in RPE cells.
• HDAC11 overexpression correlated with reduced chromatin accessibility, suggesting its involvement in AMD pathology.

Conclusions:

• Epigenetic alterations, particularly in RPE chromatin accessibility, are implicated in AMD onset and progression.
• Cigarette smoke exposure induces epigenetic changes relevant to AMD.
• HDAC11 represents a potential therapeutic target for mitigating AMD progression.