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

机译:长时间升高眼压会导致小鼠视网膜神经节细胞丢失和视网膜功能异常

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摘要

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.
机译:这项研究的目的是评估长期眼压(IOP)升高对实验性青光眼小鼠模型的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提高眼压。 24周后通过重新注射维持。每周用回弹眼压计测量眼压48周。组织学通过逆行标记和抗体染色的组合进行评估。用暗适应性视网膜电图(ERG)评估视网膜生理和功能。在珠子注射后24和48周,对注射珠子的动物和各种对照进行比较。在整个研究中,眼压升高。注射小珠后24和48周,眼压升高导致视网膜神经节细胞(RGCs)减少,轴向长度增加。与以前的研究类似,在两个时间点,通过珠子注射的眼睛的ERG的b波振幅均增加到相同的程度。当归一化为增加的b波振幅时,在24周和48周时,暗视阈值反应(pSTR)的正振幅(一种RGC电功能的量度)均减小。在第48周,即使没有正常化,pSTR幅度也降低了,提示更严重的RGC功能障碍。我们得出的结论是,注射聚苯乙烯珠和透明质酸钠会导致慢性IOP升高,从而导致表型稳定b波振幅增加和进行性pSTR振幅减少,以及RGC损失和轴向长度延长。

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