Metabolomics Analysis of Human Vitreous in Diabetic Retinopathy and Rhegmatogenous Retinal Detachment
Metabolomics Analysis of Human Vitreous in Diabetic Retinopathy and Rhegmatogenous Retinal Detachment
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DOI：
10.1021/acs.jproteome.8b00169
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发表时间：
2018-07-01
影响因子：
4.4
通讯作者：
Reisz, Julie A.
中科院分区：
文献类型：
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作者：
Haines, Nathan R.;Manoharan, Niranjan;Reisz, Julie A.
玻璃体液是一种高度水状的眼液，与视网膜和晶状体连接并提供形状。它的分子组成提供了眼睛生理状态的读数。细胞代谢的变化是玻璃体视网膜病变的基础，但尽管常规手术收集玻璃体，但仅描述了人类患者玻璃体代谢的有限报告。通过基于非靶向质谱的代谢组学，对来自孔源性视网膜脱离 (n = 25) 和增殖性糖尿病视网膜病变 (n = 9) 患者的玻璃体样本以及对照人类玻璃体样本 (n = 8) 进行了分析。在糖尿病视网膜病变玻璃体中观察到了深刻的变化，包括葡萄糖代谢的改变和磷酸戊糖途径的激活，该途径提供了还原当量来对抗氧化应激。此外，糖尿病视网膜病变中的嘌呤代谢发生改变，在产生氧化剂的反应中黄嘌呤减少，相关嘌呤（肌苷、次黄嘌呤、尿酸盐、尿囊酸盐）水平升高。相反，视网膜脱离患者的玻璃体代谢谱与对照组相似。总的来说，我们的结果表明糖尿病视网膜病变中玻璃体代谢的重新布线是氧化应激等疾病特征的基础，并进一步说明了玻璃体代谢特征如何受到疾病的影响。
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.