Abstract
Purpose :
Age related macular degeneration (AMD) is a leading cause of blindness in aging people. The pathogenesis of the disease remains poorly understood and was regarded as a multifactorial disease caused by metabolic compromise interacting with senescence. Assessing metabolomic alterations in young and aging laser-induced choroidal neovascularization model rats can provide insight on its pathogenesis.
Methods :
Choroidal neo-vascularization (CNV) was induced in young(7-week-old) and aged(24-month-old) Brown Norway rats. Seven days later, Micron IV Retinal Imaging Microscope was used to detect the formation of CNV. All rats were sacrificed and whole retina was collected for global untargeted metabolomics study using ultra-high-performance liquid chromatography tandem-mass spectrometry. Principle component analysis and volcano plot were analyzed using MetaboAnalyst. Changed metabolites from Volcano plot were further enriched for pathways using Enrichment Analysis from for univariate analysis, the significance of differences was determined by unpaired two-tailed t tests or analysis of variance with Bonferroni post hoc test.
Results :
The aged rat showed a much larger area of CNV than young rats (0.92±0.56mm2 vs. 1.48±0.65mm2, P<0.05). A total of 103 metabolites were significantly changed metabolites between young and old CNV retinas. Fatty acid metabolism, Glucose metabolism (TCA cycle) and amino acid metabolism (alanine, aspartate and glutamate metabolism) were the major pathways that were affected. For specific metabolites, stearoyl carnitine and oleoyl carnitine were the most increased. However, lactic acid, glutamic acid, acetylcarnitine, glutathione (oxidized) and Taurinein old retinas were reduced in the old retina.
Conclusions :
In conclusion, the aging eye is more likely to reduce CNV, which maybe correlated with metabolic changes in old retinas. These changes may be attributed to dysregulated mitochondrial metabolism, glucose metabolism and impaired the ability of anti-oxidative stress in the aging eye.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.