Long-term Dietary Fat Intervention Affects Retinal Health in APOE Mice

Area of Science:

• Metabolic research
• Neurodegenerative disease research
• Ophthalmology

Background:

• The apolipoprotein E (APOE) genotype significantly impacts metabolic health and neurodegeneration risk, with APOE4 carriers facing increased susceptibility to Alzheimer's disease (AD) and metabolic dysfunction.
• Understanding how dietary factors interact with APOE genotype is crucial for developing targeted health strategies.

Purpose of the Study:

• To investigate the long-term effects of dietary interventions on systemic metabolism and retinal structure/function in APOE3-knock-in (KI) and APOE4-KI mice.
• To compare the differential impact of control diet (CD) and Western diet (WD) on metabolic and ocular health based on APOE genotype.

Main Methods:

• Humanized APOE3 and APOE4-KI mice were fed either a CD or WD for 2, 6, or 12 months.
• Comprehensive analyses included body weight, glucose metabolism, lipid profiles, retinal structure and function, vascular integrity, visual performance, and inflammatory markers (e.g., Il1b expression).

Main Results:

• Western diet (WD) induced earlier glucose intolerance in APOE4 mice compared to APOE3 mice.
• APOE4 mice exhibited early retinal thinning and degeneration under WD, alongside exacerbated vascular dysfunction and inflammation.
• WD-fed APOE3 mice showed more pronounced hyperlipidemia than APOE4 mice, while control diet (CD) improved glucose metabolism but did not prevent retinal dysfunction.

Conclusions:

• APOE4 genotype confers heightened vulnerability to dietary challenges, with WD significantly worsening metabolic, retinal, and vascular impairments.
• Retinal dysfunction and inflammation are key consequences of APOE4 genotype combined with poor diet.
• Findings emphasize the need for APOE genotype-specific dietary recommendations to mitigate associated health risks.