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聚乳酸-羟基乙酸共聚物微球在创建进行性神经视网膜变性青光眼动物模型中的新应用

Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration.

作者信息

Garcia-Herranz David, Rodrigo Maria Jesus, Subias Manuel, Martinez-Rincon Teresa, Mendez-Martinez Silvia, Bravo-Osuna Irene, Bonet Aina, Ruberte Jesus, Garcia-Feijoo Julian, Pablo Luis, Garcia-Martin Elena, Herrero-Vanrell Rocío

机构信息

Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM, 28040 Madrid, Spain.

Departamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), IdISSC, 28040 Madrid, Spain.

出版信息

Pharmaceutics. 2021 Feb 8;13(2):237. doi: 10.3390/pharmaceutics13020237.

DOI:10.3390/pharmaceutics13020237
PMID:33567776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7915113/
Abstract

Progressive degeneration of neuroretinal tissue with maintained elevated intraocular pressure (IOP) to simulate chronic glaucoma was produced by intracameral injections of poly (lactic-co-glycolic) acid (PLGA) microspheres (Ms) in rat eyes. The right eye of 39 rats received different sizes of PLGA-Ms (2 µL suspension; 10% /): 14 with 38-20 µm Ms (Ms38/20 model) and 25 with 20-10 µm particles (Ms20/10 model). This novel glaucoma animal model was compared to the episcleral vein sclerosis (EPI) model (25 eyes). Injections were performed at baseline, two, four and six weeks. Clinical signs, IOP, retina and optic nerve thicknesses (using in vivo optical coherence tomography; OCT), and histological studies were performed. An IOP increment was observed in all three groups, however, the values obtained from the PLGA-Ms injection resulted lower with a better preservation of the ocular surface. In fact, the injection of Ms20/10 created a gentler, more progressive, and more sustained increase in IOP. This IOP alteration was correlated with a significant decrease in most OCT parameters and in histological ganglion-cell count for the three conditions throughout the eight-week follow-up. In all cases, progressive degeneration of the retina, retinal ganglion cells and optic nerve, simulating chronic glaucoma, was detected by OCT and corroborated by histological study. Results showed an alternative glaucoma model to the well-known episcleral vein model, which was simpler to perform, more reproducible and easier to monitor in vivo.

摘要

通过向大鼠眼内前房注射聚乳酸-羟基乙酸共聚物(PLGA)微球(Ms),制造神经视网膜组织进行性退变并维持眼内压(IOP)升高以模拟慢性青光眼。39只大鼠的右眼接受不同大小的PLGA-Ms(2 μL悬浮液;10%/):14只注射38 - 20 µm的Ms(Ms38/20模型),25只注射20 - 10 µm的颗粒(Ms20/10模型)。将这种新型青光眼动物模型与巩膜静脉硬化(EPI)模型(25只眼)进行比较。在基线、第2、4和6周进行注射。进行临床体征、IOP、视网膜和视神经厚度(使用体内光学相干断层扫描;OCT)以及组织学研究。在所有三组中均观察到IOP升高,然而,PLGA-Ms注射组获得的值较低,且眼表保存更好。实际上,注射Ms20/10导致IOP升高更为平缓、渐进且持续。在整个八周随访期间,三种情况下这种IOP改变与大多数OCT参数以及组织学神经节细胞计数的显著降低相关。在所有情况下,通过OCT检测到视网膜、视网膜神经节细胞和视神经的进行性退变,模拟慢性青光眼,组织学研究证实了这一点。结果显示了一种替代著名巩膜静脉模型的青光眼模型,该模型操作更简单、更具可重复性且在体内更容易监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/6011d01d2364/pharmaceutics-13-00237-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/765ee8e95319/pharmaceutics-13-00237-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/5d0e2f7edd4c/pharmaceutics-13-00237-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/56368d5c63e8/pharmaceutics-13-00237-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/0060f134b6fb/pharmaceutics-13-00237-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/dee57b4cc2b4/pharmaceutics-13-00237-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/3f3b97c9e800/pharmaceutics-13-00237-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/6011d01d2364/pharmaceutics-13-00237-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/765ee8e95319/pharmaceutics-13-00237-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/052c4f325ce0/pharmaceutics-13-00237-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/5d0e2f7edd4c/pharmaceutics-13-00237-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/56368d5c63e8/pharmaceutics-13-00237-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/0060f134b6fb/pharmaceutics-13-00237-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/dee57b4cc2b4/pharmaceutics-13-00237-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/3f3b97c9e800/pharmaceutics-13-00237-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fe7/7915113/6011d01d2364/pharmaceutics-13-00237-g008.jpg

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