The use of cyclodialysis to limit exposure to elevated intraocular pressure in rat glaucoma models
The use of cyclodialysis to limit exposure to elevated intraocular pressure in rat glaucoma models
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DOI：
10.1016/j.exer.2005.10.032
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发表时间：
2006-07-01
影响因子：
3.4
通讯作者：
Morrison, John C.
中科院分区：
文献类型：
--
作者：
Johnson, Elaine C.;Cepurna, William O.;Morrison, John C.
眼压升高是青光眼最常见的危险因素，控制眼压是目前临床青光眼治疗的目标。然而，最近的临床研究已经证明，即使在治疗性降低IOP后，许多患者的青光眼性视野丧失仍可能进展。在大鼠中实验性升高IOP通常用于建立人青光眼损伤模型。然而，目前还没有啮齿动物模型用于在具有明显控制的lop的眼睛中的青光眼进展的临床情况。本研究的目的是评估手术睫状体脱离术在大鼠眼中产生长期的、非损伤性的IOP降低以及在实验性眼压升高的眼中稳定地使IOP正常化的能力。为了进行睫状体分离，由皮下注射针制成钝的刮刀，并用于将睫状体的一部分与巩膜分离，打开进入脉络膜上腔的通道以允许房水流出。用高渗盐水单侧注射造成大鼠实验性高眼压。正常眼睫状体脱离导致IOP平均降低40 +/- 4%，没有明显的低眼压。眼压降低可持续至少6个月。单次睫状体脱离手术后视网膜或视神经损伤的风险最小，这一点可通过四种损伤反应性视网膜mRNA水平不变和视神经形态正常来证明。实验性眼压升高眼的睫状体脱离导致眼压正常化，分别在88%和53%的眼中持续7天和21天。此外，在手术前IOP升高累积剂量相同的眼中，通过睫状体分离成功使IOP正常化导致的视神经损伤显著低于IOP控制无效的眼中所见的视神经损伤（p = 0.03）。这些研究表明，睫状体分离提供了一种简单、无损伤的方法来降低大鼠实验性升高的IOP，该方法可用于模拟先前因压力而受损的眼睛的临床情况。这一发现为识别和研究与脑卒中进展相关的分子过程以及在临床相关情况下测试潜在的神经保护疗法提供了新的机会。(c)2006爱思唯尔有限公司保留所有权利。
Elevated intraocular pressure (IOP) is the most common risk factor for glaucoma and pressure control is the goal of current clinical glaucoma therapy. Yet, recent clinical studies have documented that, even after therapeutic lowering of IOP, glaucomatous visual field loss can progress in many patients. Experimental elevation of IOP in the rat is commonly used to model human glaucomatous injury. However, there currently is no rodent model for the clinical situation of glaucomatous progression in eyes with apparently controlled lop. The purpose of this study was to evaluate the ability of surgical cyclodialysis to produce both prolonged, non-injurious reduction of IOP in rat eyes and to stably normalize IOP in eyes with experimental pressure elevation. To perform cyclodialysis, a blunted spatula was fashioned from a hypodermic needle and used to separate a portion of the ciliary body from the sclera, opening a channel into the suprachoroidal space to allow aqueous outflow. Experimental IOP elevation was produced in rats by unilateral injection of hypertonic saline. Cyclodialysis in normal eyes resulted in an average 40 +/- 4% reduction in IOP, without marked hypotony. IOP lowering could be sustained for at least 6 months. The risk of retinal or optic nerve injury following a single cyclodialysis procedure was minimal as evidenced by unaltered levels of four injury-responsive retinal mRNAs and by normal optic nerve morphology. Cyclodialysis in eyes with experimental IOP elevation resulted in IOP normalization that was sustained for durations of 7 and 21 days in 88% and 53% of eyes, respectively. In addition, in eyes with the same cumulative dose of elevated IOP prior to the procedure, successful IOP normalization by cyclodialysis resulted in significantly less optic nerve injury than that seen in eyes in which IOP control was ineffective (p = 0.03). These studies show that cyclodialysis provides a simple, non-injurious method to reduce experimentally elevated IOP in rats that can be used to model the clinical situation of eyes previously damaged by pressure. This toot offers new opportunities for identifying and studying the molecular processes associated with glaucomatous progression and for testing potential neuroprotective therapies in a clinically relevant situation. (c) 2006 Elsevier Ltd. All rights reserved.