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用于活体视网膜中NLRP3炎性小体靶向可视化的新型光学成像探针。

Novel Optical Imaging Probe for the Targeted Visualization of NLRP3 Inflammasomes in Living Retina.

作者信息

Uddin Md Imam, Dieckmann Blake, Soliman Sarah

机构信息

Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.

Department of Biomedical Engineering, Vanderbilt University School of Engineering, Nashville, Tennessee 37235, United States.

出版信息

J Med Chem. 2025 Aug 14;68(15):16034-16047. doi: 10.1021/acs.jmedchem.5c00999. Epub 2025 Aug 4.

DOI:10.1021/acs.jmedchem.5c00999
PMID:40758602
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12362592/
Abstract

Activation of the NLR-family pyrin domain-containing 3 (NLRP3) inflammasome has been associated with diabetic retinopathy progression. We have synthesized a highly sensitive molecular imaging probe, InflammaProbe-2, as an early detection diagnostic tool for the in vivo molecular imaging of NLRP3 inflammasomes in living diabetic retina. The ability of InflammaProbe-2 for the targeted visualization of the NLRP3 inflammasome was assessed using an enzyme-linked immunosorbent assay (ELISA) by comparing its ability to inhibit the NLRP3-mediated secretion of IL-1β. InflammaProbe-2 was able to visualize NLRP3 inflammasomes in ARPE-19 cells treated under hyperglycemia as well as inflammatory conditions. Furthermore, InflammaProbe-2-dependent in vivo and ex vivo imaging of the NLRP3 inflammasome was achieved via fluorescence enhancement in streptozotocin (STZ)-induced diabetic retinopathy. In addition, the toxicity of InflammaProbe-2 was assessed in vitro and in vivo studies. InflammaProbe-2 showed no significant changes in the a-wave and b-wave amplitudes of their electrical response to flashes of light.

摘要

含NLR家族pyrin结构域蛋白3（NLRP3）炎性小体的激活与糖尿病视网膜病变的进展有关。我们合成了一种高灵敏度的分子成像探针InflammaProbe-2，作为一种早期检测诊断工具，用于对活体糖尿病视网膜中的NLRP3炎性小体进行体内分子成像。通过比较其抑制NLRP3介导的白细胞介素-1β分泌的能力，使用酶联免疫吸附测定（ELISA）评估了InflammaProbe-2对NLRP3炎性小体进行靶向可视化的能力。InflammaProbe-2能够在高血糖以及炎症条件下处理的ARPE-19细胞中可视化NLRP3炎性小体。此外，通过链脲佐菌素（STZ）诱导的糖尿病视网膜病变中的荧光增强，实现了InflammaProbe-2依赖的NLRP3炎性小体的体内和体外成像。此外，在体外和体内研究中评估了InflammaProbe-2的毒性。InflammaProbe-2对闪光的电反应的a波和b波振幅没有显著变化。

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