Mol Nutr Food Res. 2023 Jul 25:e2300080. doi: 10.1002/mnfr.202300080. Online ahead of print.
SCOPE: Choroidal neovascularization (CNV) is age-related macular degeneration’s (AMD) main pathological change. High-fat diet (HFD) is associated with a form of CNV; however, the specific mechanism is unclear. Mitochondrial dysfunction, characterized by abnormal acylcarnitine, occurs during metabolic screening of serum or other body tissues in AMD. This study investigates HFD’s role in retinal and retinal pigment epithelium (RPE)/choroidal acylcarnitine metabolism in CNV formation.
METHODS AND RESULTS: Chow diet and HFD-BN rats are laser-treated to induce CNV. Acylcarnitine species are quantitatively characterized by ultrahigh-performance liquid chromatography-tandem mass spectrometry. Optical coherence tomography and fundus fluorescein angiography evaluate CNV severity. HFD promotes weight gain, dyslipidemia, and CNV formation. In CNV rats, few medium-chain fatty acids (MCFAs) acylcarnitine in the RPE/choroid are initially affected. When an HFD is administered to these, even MCFA acylcarnitine in the RPE/choroid is found to decline. However, in the retina, odd acylcarnitines are increased, revealing “an opposite” change within the RPE/choroid, accompanied by influencing glycolytic key enzymes. The HFD+CNV group incorporated fewer long-chain acylcarnitines, like C18:2, into the retina than controls.
CONCLUSIONS: HFD hastens choroidal neovascularization. The study comprehensively documented acylcarnitine profiles in a CNV rat model. Acylcarnitine’s odd-even and carbon-chain length properties may guide future therapeutics.