衰老视网膜代谢特征的鉴定。

Identification of the Metabolic Signature of Aging Retina.

机构信息

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Transl Vis Sci Technol. 2024 Aug 1;13(8):8. doi: 10.1167/tvst.13.8.8.

DOI:10.1167/tvst.13.8.8

PMID:39102240

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11309042/

Abstract

PURPOSE

This study aims to explore the metabolic signature of aging retina and identify the potential metabolic biomarkers for the diagnosis of retinal aging.

METHODS

Retinal samples were collected from both young (two months) and aging (14 months) mice to conduct an unbiased metabolic profiling. Liquid chromatography-tandem mass spectrometry analysis was conducted to screen for the metabolic biomarkers and altered signaling pathways associated with retinal aging.

RESULTS

We identified 166 metabolites differentially expressed between young and aged retinas using a threshold of orthogonal projection to latent structures discriminant analysis variable importance in projection >1 and P < 0.05. These metabolites were significantly enriched in several metabolic pathways, including purine metabolism, citrate cycle, phenylalanine, tyrosine and tryptophan biosynthesis, glycerophospholipid metabolism, and alanine, aspartate and glutamate metabolism. Among these significantly enriched pathways, glycerophospholipid metabolites emerged as promising candidates for retinal aging biomarkers. We assessed the potential of these metabolites as biomarkers through an analysis of their sensitivity and specificity, determined by the area under the receiver-operating characteristic (ROC) curves. Notably, the metabolites like PC (15:0/22:6), PC (17:0/14:1), LPC (P-16:0), PE (16:0/20:4), and PS (17:0/16:1) demonstrated superior performance in sensitivity, specificity, and accuracy in predicting retinal aging.

CONCLUSIONS

This study sheds light on the molecular mechanisms underlying retinal aging by identifying distinct metabolic profiles and pathways. These findings provide a valuable foundation for developing future clinical applications in diagnosing, identifying, and treating age-related retinal degeneration.

TRANSLATIONAL RELEVANCE

This study sheds light on novel metabolic profiles and biomarkers in aging retinas, potentially paving the way for targeted interventions in preventing, diagnosing, and treating age-related retinal degeneration and other retinal diseases.

摘要

目的

本研究旨在探索衰老视网膜的代谢特征，并确定潜在的代谢生物标志物，用于诊断视网膜衰老。

方法

收集来自年轻（两个月）和衰老（14 个月）小鼠的视网膜样本，进行无偏代谢谱分析。采用正交投影到潜在结构判别分析变量重要性投影（orthogonal projection to latent structures discriminant analysis variable importance in projection，O-PLS-DA）>1 和 P < 0.05 的阈值，筛选与视网膜衰老相关的代谢生物标志物和改变的信号通路。

结果

我们使用 O-PLS-DA 方法，发现了 166 种在年轻和衰老视网膜之间差异表达的代谢物，其阈值为正交投影到潜在结构判别分析变量重要性投影（orthogonal projection to latent structures discriminant analysis variable importance in projection，O-PLS-DA）>1 和 P < 0.05。这些代谢物在几个代谢途径中显著富集，包括嘌呤代谢、柠檬酸循环、苯丙氨酸、酪氨酸和色氨酸生物合成、甘油磷脂代谢以及丙氨酸、天冬氨酸和谷氨酸代谢。在这些显著富集的途径中，甘油磷脂代谢物成为有希望的视网膜衰老生物标志物候选物。我们通过分析这些代谢物的敏感性和特异性（通过接收者操作特征（receiver operating characteristic，ROC）曲线下的面积确定），评估了它们作为生物标志物的潜力。值得注意的是，PC（15:0/22:6）、PC（17:0/14:1）、LPC（P-16:0）、PE（16:0/20:4）和 PS（17:0/16:1）等代谢物在预测视网膜衰老方面表现出较高的敏感性、特异性和准确性。