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.
方法:来自2型糖尿病和非糖尿病受试者的玻璃体样本,验尸后收集,使用液相色谱-质谱法进行分析。进行通路富集和基因本体论分析以鉴定失调的通路并表征蛋白质功能。
结果:通路分析显示与糖尿病相关的多种代谢和信号通路失调,包括甘油脂代谢,组氨酸代谢,和Wnt信号。基因本体论分析确定了与炎症有关的蛋白质,免疫反应失调,和钙信号。值得注意的是,蛋白质,如肌醇1,4,5-三磷酸受体2型(ITPR2),钙稳态内质网蛋白(CHERP),和Coronin-1A(CORO1A)在糖尿病玻璃体中明显上调,涉及异常的钙信号,炎症反应,和DR中的细胞骨架重组。
结论:我们的研究为DR的复杂机制提供了有价值的见解,并强调了炎症的重要性,免疫失调,和疾病进展中的代谢紊乱。将特定蛋白质鉴定为潜在的生物标志物强调了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并将研究结果转化为临床实践至关重要。