PPARα deficiency exacerbates retinal pathological changes and dysfunction in high-fat diet mice

Area of Science:

• Ophthalmology
• Metabolic Research
• Molecular Biology

Background:

• High-fat diets (HFD) are linked to various metabolic disorders.
• Retinal dysfunction and pathological changes can occur due to metabolic disturbances.
• Peroxisome proliferator-activated receptor-alpha (PPARα) plays a role in lipid metabolism.

Purpose of the Study:

• To investigate the impact of HFD on retinal pathology and function.
• To determine the role of PPARα in HFD-induced retinal changes using PPARα knockout mice.

Main Methods:

• Mice (C57BL/6J and PPARα knockout) were fed HFD or standard diet for four months.
• Retinal triglycerides, malondialdehyde (MDA), and protein/mRNA expression were analyzed.
• Retinal function was assessed using electroretinography.

Main Results:

• HFD increased retinal fatty acid oxidation, triglyceride accumulation, and weight.
• PPARα deficiency exacerbated HFD-induced lipid abnormalities, inflammation (NF-κB pathway), and oxidative stress.
• HFD-induced retinal ganglion cell (RGC) apoptosis and retinal dysfunction (reduced wave amplitudes) were worsened by PPARα knockout.

Conclusions:

• PPARα knockout intensifies lipid metabolic abnormalities in the retina under HFD conditions.
• The absence of PPARα amplifies inflammatory responses, oxidative stress, and apoptosis in HFD-fed mouse retinas.
• PPARα deficiency significantly contributes to HFD-induced retinal dysfunction.