Metabolomics Analysis of Human Vitreous in Diabetic Retinopathy and Rhegmatogenous Retinal Detachment

The vitreous humor is a highly aqueous
eye fluid interfacing with
the retina and lens and providing shape. Its molecular composition
provides a readout for the eye’s physiological status. Changes
in cellular metabolism underlie vitreoretinal pathologies, but despite
routine surgical collection of vitreous, only limited reports of metabolism
in the vitreous of human patients have been described. Vitreous samples
from patients with rhegmatogenous retinal detachment (n = 25) and proliferative diabetic retinopathy (n = 9) were profiled along with control human vitreous samples (n = 8) by untargeted mass-spectrometry-based metabolomics.
Profound changes were observed in diabetic retinopathy vitreous, including
altered glucose metabolism and activation of the pentose phosphate
pathway, which provides reducing equivalents to counter oxidative
stress. In addition, purine metabolism was altered in diabetic retinopathy,
with decreased xanthine and elevated levels of related purines (inosine,
hypoxanthine, urate, allantoate) generated in oxidant-producing reactions.
In contrast, the vitreous metabolite profiles of retinal detachment
patients were similar to controls. In total, our results suggest a
rewiring of vitreous metabolism in diabetic retinopathy that underlies
disease features such as oxidative stress and furthermore illustrates
how the vitreous metabolic profile may be impacted by disease.

玻璃体（vitreous humor）是一种高含水的眼内液，毗邻视网膜与晶状体并维持眼球形态。其分子组成可反映眼部的生理状态。细胞代谢异常是玻璃体视网膜疾病的病理基础，但尽管临床常规手术可收集玻璃体样本，目前针对人类患者玻璃体代谢的相关报道仍较为有限。本研究采用基于质谱的非靶向代谢组学（untargeted mass-spectrometry-based metabolomics）技术，对25例孔源性视网膜脱离（rhegmatogenous retinal detachment）患者、9例增殖性糖尿病视网膜病变（proliferative diabetic retinopathy）患者及8例健康对照的玻璃体样本进行代谢谱分析。结果显示，增殖性糖尿病视网膜病变患者的玻璃体代谢谱存在显著改变，包括葡萄糖代谢紊乱以及磷酸戊糖途径（pentose phosphate pathway）激活——该途径可产生还原当量以对抗氧化应激。此外，增殖性糖尿病视网膜病变患者的嘌呤代谢（purine metabolism）亦出现异常：黄嘌呤（xanthine）水平降低，而氧化反应生成的相关嘌呤代谢物肌苷（inosine）、次黄嘌呤（hypoxanthine）、尿酸盐（urate）、尿囊素酸（allantoate）水平显著升高。与之相比，孔源性视网膜脱离患者的玻璃体代谢谱与健康对照组无显著差异。综上，本研究结果表明，增殖性糖尿病视网膜病变患者的玻璃体代谢发生重编程，该改变是该病氧化应激等病理特征的核心基础，同时也揭示了玻璃体代谢谱可随疾病状态发生动态变化。