Inflammatory adipose activates a nutritional immunity pathway leading to retinal dysfunction.

Area of Science:

• Ophthalmology
• Immunology
• Metabolism

Background:

• Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in individuals over 50.
• Retinal pigment epithelial (RPE) cell dysfunction and death characterize AMD.
• Iron accumulation in RPE cells is observed in AMD, and iron overload can induce RPE cell death.

Purpose of the Study:

• To investigate the mechanism of RPE iron accumulation in AMD.
• To explore the link between obesity, inflammation, and RPE iron dysregulation.

Main Methods:

• Investigated the role of high-fat-diet-induced obesity and interleukin-1β (IL-1β) in RPE iron metabolism.
• Utilized RNA sequencing (RNA-seq) to analyze gene expression in human AMD choroid and retina samples.
• Examined the cellular iron sequestration response (CISR) pathway.

Main Results:

• High-fat-diet-induced obesity upregulates IL-1β, which alters RPE iron importer and exporter expression.
• This leads to iron accumulation, oxidative stress, and RPE dysfunction, a process termed CISR.
• AMD microglia and macrophages exhibit hallmarks of the CISR pathway.

Conclusions:

• Inflammation, particularly IL-1β driven by obesity, contributes to RPE iron accumulation and pathology in AMD via the CISR.
• The findings suggest a link between inflamed adipose tissue and AMD pathogenesis.