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长期给予类固醇对大鼠眼部前段和后段的影响及其对抗青光眼药物的反应性。

Anterior and posterior segment changes in rat eyes with chronic steroid administration and their responsiveness to antiglaucoma drugs.

作者信息

Razali Norhafiza, Agarwal Renu, Agarwal Puneet, Kapitonova Marina Y, Kannan Kutty Methil, Smirnov Alexey, Salmah Bakar Nor, Ismail Nafeeza M

机构信息

Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia; Faculty of Medicine, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor, Malaysia.

Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia; Faculty of Medicine, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor, Malaysia.

出版信息

Eur J Pharmacol. 2015 Feb 15;749:73-80. doi: 10.1016/j.ejphar.2014.11.029. Epub 2014 Dec 4.

Abstract

Steroid-induced ocular hypertension (SIOH) is associated with topical and systemic use of steroids. However, SIOH-associated anterior and posterior segment morphological changes in rats have not been described widely. Here we describe the pattern of intraocular pressure (IOP) changes, quantitative assessment of trabecular meshwork (TM) and retinal morphological changes and changes in retinal redox status in response to chronic dexamethasone treatment in rats. We also evaluated the responsiveness of steroid-pretreated rat eyes to 5 different classes of antiglaucoma drugs that act by different mechanisms. Up to 80% of dexamethasone treated animals achieved significant and sustained IOP elevation. TM thickness was significantly increased and number of TM cells was significantly reduced in SIOH rats compared to the vehicle-treated rats. Quantitative assessment of retinal morphology showed significantly reduced thickness of ganglion cell layer (GCL) and inner retina (IR) in SIOH rats compared to vehicle-treated rats. Estimation of retinal antioxidants including catalase, superoxide dismutase and glutathione showed significantly increased retinal oxidative stress in SIOH animals. Furthermore, steroid-treated eyes showed significant IOP lowering in response to treatment with 5 different drug classes. This indicated the ability of SIOH eyes to respond to drugs acting by different mechanisms. In conclusion, SIOH was associated with significant morphological changes in TM and retina and retinal redox status. Additionally, SIOH eyes also showed IOP lowering in response to drugs that act by different mechanisms of action. Hence, SIOH rats appear to be an inexpensive and noninvasive model for studying the experimental antiglaucoma drugs for IOP lowering and neuroprotective effects.

摘要

类固醇诱导性青光眼(SIOH)与局部和全身使用类固醇有关。然而,SIOH相关的大鼠眼前后段形态变化尚未得到广泛描述。在此,我们描述了大鼠慢性地塞米松治疗后眼内压(IOP)变化模式、小梁网(TM)定量评估、视网膜形态变化以及视网膜氧化还原状态变化。我们还评估了经类固醇预处理的大鼠眼对5种不同作用机制的抗青光眼药物的反应性。高达80%的地塞米松治疗动物实现了显著且持续的IOP升高。与赋形剂处理的大鼠相比,SIOH大鼠的TM厚度显著增加,TM细胞数量显著减少。视网膜形态的定量评估显示,与赋形剂处理的大鼠相比,SIOH大鼠的神经节细胞层(GCL)和视网膜内层(IR)厚度显著降低。对包括过氧化氢酶、超氧化物歧化酶和谷胱甘肽在内的视网膜抗氧化剂的评估显示,SIOH动物的视网膜氧化应激显著增加。此外,经类固醇处理的眼睛在接受5种不同药物类别的治疗后IOP显著降低。这表明SIOH眼对不同作用机制的药物有反应能力。总之,SIOH与TM和视网膜的显著形态变化以及视网膜氧化还原状态有关。此外,SIOH眼对不同作用机制的药物也表现出IOP降低。因此,SIOH大鼠似乎是一种用于研究降低IOP和神经保护作用的实验性抗青光眼药物的廉价且非侵入性模型。

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