Abstract
Purpose :
Mitochondrial dysfunction, characterized by abnormal acylcarnitine, has been found during metabolic screening of serum or other body tissues in wet age-related macular degeneration (AMD). Although regarded as potential diagnostic markers, whether defect in acylcarnitine metabolism contributes to the pathophysiology of wet AMD on retina and RPE/choroid remains unclear. This study aimed to investigate carnitine shuttle pathway in a laser induced choroidal neovascularization (CNV) model.
Methods :
Chow Diet (CD) and high fat diet (HFD) BN rats were laser treated to induce CNV. A global untargeted metabolomics study was performed between NC and CNV model. Ultrahigh-performance liquid chromatography tandem mass spectrometry was used to quantitatively characterize acylcarnitine species. OCT and FFA were employed to evaluate CNV severity. Western blotting was used to analyze key glycolytic enzymes.
Results :
In the CD+CNV model, a few medium chain fatty acid (MCFA) acylcarnitine in the RPE/Choroid were initially affected; when high fat diet was given to the CNV model, even MCFA acylcarnitine in the RPE /Choroid was found to decline, compared with the CNV group. By contrast, in the retina, odd acylcarnitine, proposed as potential biomarkers for the metabolic syndrome, showed an upward trend revealing "reverse or separate" change with RPE/Choroid, accompanied by influencing glycolytic key enzymes. While comparing HFD+CNV with the control group, we found that few, long-chain acyl carnitine, such as (C18:2) was characterized by incorporation in the retina.
Conclusions :
In conclusion, we documented comprehensive acylcarnitine profiles in CNV model which expands the palette of acylcarnitine with treatment potential, derived from odd-even and carbon chain length.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.