糖尿病性视网膜病变
下调和上调
医学
视网膜
小胶质细胞
阿柏西普
细胞外基质
视网膜
糖尿病
新生血管
炎症
癌症研究
药理学
血管生成
免疫学
细胞生物学
眼科
生物
内分泌学
神经科学
内科学
贝伐单抗
生物化学
基因
化疗
作者
Hao Wu,Fang Xu,Yunfang Luo,Yibao Zhang,Min Tang
出处
期刊:Biofabrication
[IOP Publishing]
日期:2023-09-27
卷期号:15 (4): 045025-045025
标识
DOI:10.1088/1758-5090/acfb3c
摘要
Abstract Diabetic retinopathy (DR) is a common diabetes complication leading to vision impairment or blindness due to retinal vasculature alterations. Hyperglycemia induces structural alterations, inflammation, and angiogenic factor upregulation. Current treatments targeting vascular endothelial growth factor are insufficient for approximately 20% of DR patients, necessitating alternative approaches. Microglia (MG), essential for retinal homeostasis, remains underexplored in DR. This study used digital light processing bioprinting to construct a 3D coculture model of endothelial cells (ECs) and MG under varying glucose conditions, with a hydrogel stiffness of 4.6–7.1 kPa to mimic the extracellular matrix property of retina plexiform. Our results showed that high glucose levels influenced both EC and microglial phenotypes, gene expression, and angiogenic potential. Increasing glucose from 5 mM to 25 mM reduces drug efficacy by 17% for Aflibercept in EC monoculture, and 25% and 30% for Aflibercept and Conbercept in EC-MG coculture, respectively, suggesting that diabetic condition and MG presence could interfere with drug responses. In conclusion, our findings emphasize the importance of cellular interactions and microenvironmental factors in DR therapy, aiming to identify novel strategies and improve understanding of MG’s role in disease pathogenesis.
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