FarmaChusLab Group, Health Research Institute of Santiago de Compostela (FIDIS), 15706 Santiago de Compostela, Spain; Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain.
Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain; Molecular Imaging Biomarkers and Theragnosis Lab, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain; Nuclear Medicine Service and Molecular Imaging Group, Health Research Institute of Santiago de Compostela (FIDIS), 15706 Santiago de Compostela, Spain.
Int J Pharm. 2024 Sep 5;662:124516. doi: 10.1016/j.ijpharm.2024.124516. Epub 2024 Jul 25.
Uveitis is a group of inflammatory ocular pathologies. Endotoxin-Induced Uveitis (EIU) model represent a well-known model induced by administration of Lipopolysaccharide (LPS). The aim is to characterize two models of EIU through two routes of administration with novel noninvasive imaging techniques. 29 rats underwent Intraocular Pressure (IOP) measurements, Optical Coherence Tomography (OCT), proteomic analysis, and Positron Emission Tomography and Computed Tomography (PET/CT). Groups included healthy controls (C), BSS administered controls (Ci), systemically induced EIU with LPS (LPSs), and intravitreally induced EIU with LPS (LPSi) for IOP, OCT, and proteomic studies. For F-FDG PET/CT study, animals were divided into FDG-C, FDG-LPSs and FDG-LPSi groups and scanned using a preclinical PET/CT system. LPSi animals exhibited higher IOP post-induction compared to C and LPSs groups. LPSi showed increased cellular infiltrate, fibrotic membranes, and iris inflammation. Proinflammatory proteins were more expressed in EIU models, especially LPSi. PET/CT indicated higher eye uptake in induced models compared to FDG-C. FDG-LPSi showed higher eye uptake than FDG-LPSs but systemic uptake was higher in FDG-LPSs due to generalized inflammation. OCT is valuable for anterior segment assessment in experimental models. F-FDG PET/CT shows promise as a noninvasive biomarker for ocular inflammatory diseases. Intravitreal induction leads to higher ocular inflammation. These findings offer insights for future inflammatory disease research and drug studies.
葡萄膜炎是一组眼部炎症性疾病。内毒素诱导的葡萄膜炎（EIU）模型是一种通过给予脂多糖（LPS）诱导的知名模型。目的是通过两种新型非侵入性成像技术来描述两种 EIU 模型。29 只大鼠进行了眼压（IOP）测量、光学相干断层扫描（OCT）、蛋白质组学分析以及正电子发射断层扫描和计算机断层扫描（PET/CT）。实验组包括健康对照组（C）、给予缓冲盐溶液对照组（Ci）、全身给予 LPS 诱导的 EIU 组（LPSs）和玻璃体内给予 LPS 诱导的 EIU 组（LPSi），用于 IOP、OCT 和蛋白质组学研究。对于 F-FDG PET/CT 研究，动物分为 FDG-C、FDG-LPSs 和 FDG-LPSi 组，并使用临床前 PET/CT 系统进行扫描。与 C 和 LPSs 组相比，LPSi 动物在诱导后表现出更高的眼压。LPSi 显示出更多的细胞浸润、纤维性膜和虹膜炎症。在 EIU 模型中，促炎蛋白表达更高，尤其是 LPSi。与 FDG-C 相比，诱导模型的眼部摄取更高。与 FDG-LPSs 相比，FDG-LPSi 显示出更高的眼部摄取，但由于全身性炎症，FDG-LPSs 的全身摄取更高。OCT 对实验模型的前节评估具有价值。F-FDG PET/CT 作为眼部炎症性疾病的非侵入性生物标志物具有广阔前景。玻璃体内诱导导致更高的眼部炎症。这些发现为未来的炎症性疾病研究和药物研究提供了见解。
