Comparative Proteomic Analysis of Type 2 Diabetic versus Non-Diabetic Vitreous Fluids

Life Pub Date : 2024-07-16 DOI:10.3390/life14070883
Abdulaziz H. Alanazi, Shengshuai Shan, S. P. Narayanan, P. R. Somanath
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Abstract

Background: Diabetic retinopathy (DR) is a leading cause of vision loss, with complex mechanisms. The study aimed to comprehensively explore vitreous humor of diabetic and non-diabetic individuals, paving the way for identifying the potential molecular mechanisms underlying DR. Methods: Vitreous samples from type 2 diabetic and non-diabetic subjects, collected post-mortem, were analyzed using liquid chromatography–mass spectrometry. Pathway enrichment and gene ontology analyses were conducted to identify dysregulated pathways and characterize protein functions. Results: Pathway analysis revealed dysregulation in multiple metabolic and signaling pathways associated with diabetes, including glycerolipid metabolism, histidine metabolism, and Wnt signaling. Gene ontology analysis identified proteins involved in inflammation, immune response dysregulation, and calcium signaling. Notably, proteins such as Inositol 1,4,5-trisphosphate receptor type 2 (ITPR2), Calcium homeostasis endoplasmic reticulum protein (CHERP), and Coronin-1A (CORO1A) were markedly upregulated in diabetic vitreous, implicating aberrant calcium signaling, inflammatory responses, and cytoskeletal reorganization in DR. Conclusions: Our study provides valuable insights into the intricate mechanisms underlying DR and highlights the significance of inflammation, immune dysregulation, and metabolic disturbances in disease progression. Identification of specific proteins as potential biomarkers underscores the multifactorial nature of DR. Future research in this area is vital for advancing therapeutic interventions and translating findings into clinical practice.
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2 型糖尿病玻璃体液与非糖尿病玻璃体液的蛋白质组对比分析
背景:糖尿病视网膜病变(DR)是视力丧失的主要原因之一,其发病机制十分复杂。本研究旨在全面探讨糖尿病患者和非糖尿病患者的玻璃体,为确定糖尿病视网膜病变的潜在分子机制铺平道路。研究方法采用液相色谱-质谱联用技术分析死后采集的 2 型糖尿病患者和非糖尿病患者的玻璃体样本。进行通路富集和基因本体分析,以确定失调通路和蛋白质功能特征。结果通路分析表明,与糖尿病相关的多种代谢和信号通路出现失调,包括甘油脂代谢、组氨酸代谢和Wnt信号转导。基因本体分析发现了涉及炎症、免疫反应失调和钙信号转导的蛋白质。值得注意的是,1,4,5-三磷酸肌醇受体 2 型(ITPR2)、钙平衡内质网蛋白(CHERP)和冠蛋白-1A(CORO1A)等蛋白在糖尿病玻璃体内明显上调,这与 DR 中异常的钙信号转导、炎症反应和细胞骨架重组有关。结论:我们的研究为了解 DR 的复杂机制提供了有价值的见解,并强调了炎症、免疫失调和代谢紊乱在疾病进展中的重要性。作为潜在生物标志物的特定蛋白质的鉴定强调了 DR 的多因素性质。该领域的未来研究对于推进治疗干预措施和将研究结果转化为临床实践至关重要。
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