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眼压长期升高会导致小鼠视网膜神经节细胞丢失和视网膜功能异常。

Prolonged elevation of intraocular pressure results in retinal ganglion cell loss and abnormal retinal function in mice.

作者信息

Khan A Kareem, Tse Dennis Y, van der Heijden Meike E, Shah Priya, Nusbaum Derek M, Yang Zhuo, Wu Samuel M, Frankfort Benjamin J

机构信息

Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.

Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; School of Optometry, Hong Kong Polytechnic University, Hong Kong.

出版信息

Exp Eye Res. 2015 Jan;130:29-37. doi: 10.1016/j.exer.2014.11.007. Epub 2014 Nov 18.

Abstract

The purpose of this study was to assess the impact of prolonged intraocular pressure (IOP) elevation on retinal anatomy and function in a mouse model of experimental glaucoma. IOP was elevated by anterior chamber injection of a fixed combination of polystyrene beads and sodium hyaluronate, and maintained via re-injection after 24 weeks. IOP was measured weekly with a rebound tonometer for 48 weeks. Histology was assessed with a combination of retrograde labeling and antibody staining. Retinal physiology and function was assessed with dark-adapted electroretinograms (ERGs). Comparisons between bead-injected animals and various controls were conducted at both 24 and 48 weeks after bead injection. IOP was elevated throughout the study. IOP elevation resulted in a reduction of retinal ganglion cell (RGCs) and an increase in axial length at both 24 and 48 weeks after bead injection. The b-wave amplitude of the ERG was increased to the same degree in bead-injected eyes at both time points, similar to previous studies. The positive scotopic threshold response (pSTR) amplitude, a measure of RGC electrical function, was diminished at both 24 and 48 weeks when normalized to the increased b-wave amplitude. At 48 weeks, the pSTR amplitude was reduced even without normalization, suggesting more profound RGC dysfunction. We conclude that injection of polystyrene beads and sodium hyaluronate causes chronic IOP elevation which results in phenotypes of stable b-wave amplitude increase and progressive pSTR amplitude reduction, as well as RGC loss and axial length elongation.

摘要

本研究的目的是在实验性青光眼小鼠模型中评估眼内压(IOP)长期升高对视网膜解剖结构和功能的影响。通过前房注射聚苯乙烯珠和透明质酸钠的固定组合来升高IOP,并在24周后通过再次注射维持该状态。使用回弹眼压计每周测量IOP,持续48周。通过逆行标记和抗体染色相结合的方法评估组织学。使用暗适应视网膜电图(ERG)评估视网膜生理和功能。在注射珠子后的24周和48周,对注射珠子的动物与各种对照组进行比较。在整个研究过程中IOP均升高。在注射珠子后的24周和48周,IOP升高导致视网膜神经节细胞(RGCs)减少,眼轴长度增加。与先前的研究相似,在两个时间点,注射珠子的眼睛中ERG 的b波振幅均升高到相同程度。当以升高的b波振幅进行标准化时,作为RGC电功能指标的阳性暗视阈值反应(pSTR)振幅在24周和48周时均降低。在48周时,即使不进行标准化,pSTR振幅也降低,表明RGC功能障碍更为严重。我们得出结论,注射聚苯乙烯珠和透明质酸钠会导致慢性IOP升高,从而导致b波振幅稳定增加和pSTR振幅逐渐降低的表型,以及RGC丢失和眼轴长度延长。

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