The dark phase intraocular pressure elevation and retinal ganglion cell degeneration in a rat model of experimental glaucoma
The dark phase intraocular pressure elevation and retinal ganglion cell degeneration in a rat model of experimental glaucoma
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DOI：
10.1016/j.exer.2013.04.008
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发表时间：
2013-07-01
影响因子：
3.4
通讯作者：
Caprioli, Joseph
中科院分区：
文献类型：
--
作者：
Kwong, Jacky M. K.;Vo, Nancy;Caprioli, Joseph
眼压升高被认为是导致青光眼视力恶化的主要危险因素。虽然众所周知，眼压水平在昼夜之间变化很大，但眼压升高是如何导致视网膜神经节细胞(RGC)变性的，目前仍不清楚。为了检测眼压的变化，对Brown挪威大鼠的小梁网进行改良激光光凝，每周监测明、暗期眼压约1~2次。观察眼压升高与RGC变性的关系，同时用Rbpms免疫组织化学标记技术分析RGC小体丢失情况，并对视神经轴突损伤进行半定量研究。基线清醒、暗、亮眼压分别为30.4+/-2.7和20.2+/-2.1 mm Hg。270度小梁网激光治疗5周后，平均暗眼压升高至38.2±3.2 mm Hg。但未见明显的RGC小体丢失和轴突损伤。330度小梁网激光治疗5周后，暗眼压为43.8±-4.6 mm Hg，光眼压为23±3.7 mm Hg。暗眼压累计升高277+/-86天，暗眼压累计升高113+/-50天，总眼压升高213+/-114天。5周后局部RGC小体丢失29.5+/-15.5%，中度轴索损伤。轴索损伤和RGC小体丢失与累积总眼压升高高度相关(R2分别为0.60和0.65)。RGC小体丢失(R2=0.37)和轴突损伤(R2=0.51)与累计暗眼压和眼压升高相关，而神经元损伤与RGC小体丢失(R2=0.01；轴突损伤R2=0.26)之间的相关性较弱。简单线性回归模型分析显示，累计眼压升高与视网膜神经节细胞体积丢失(P=0.009)和轴索损伤(P=0.016)之间的关系具有统计学意义。为了探讨明、暗眼压升高在视网膜神经节小体丢失和轴突损伤中的作用，分析了不同明/暗眼压因素与RGC小体丢失/轴突损伤分级的相关性，只有累计暗眼压升高与轴突损伤之间的相关性有统计学意义(P=0.033)。结果表明，累积的总眼压(明的和暗的)眼压升高是实验性青光眼大鼠模型视网膜色素上皮细胞变性的危险因素，该模型采用330度小梁网状部分激光光凝。需要进一步的研究来了解较长时间的明暗相眼压升高对视网膜神经节细胞不同隔室的退化进程的作用。(C)2013爱思唯尔有限公司。保留所有权利。
Intraocular pressure (IOP) elevation is considered as a major risk factor causing the progression of vision deterioration in glaucoma. Although it is known that the IOP level changes widely throughout the day and night, how the dark or light phase IOP, elevation contributes to retinal ganglion cell (RGC) degeneration is still largely unclear. To examine the profile of IOP, modified laser photocoagulation was applied to the trabecular meshwork of Brown Norway rats and both light and dark phase IOPs were monitored approximately 1-2 times a week. The relationship between IOP elevation and RGC degeneration was investigated while RGC body loss was analyzed with Rbpms immunolabeling on retinal wholemount and axonal injury in the optic nerve was semi-quantified. The baseline awake dark and light IOPs were 30.4 +/- 2.7 and 20.2 +/- 2.1 mmHg respectively. The average dark IOP was increased to 38.2 +/- 3.2 mmHg for five weeks after the laser treatment on 270 degrees trabecular meshwork. However, there was no significant loss of RGC body and axonal injury. After laser treatment on 330 degrees trabecular meshwork, the dark and light IOPs were significantly increased to 43.8 +/- 4.6 and 23 +/- 3.7 mmHg respectively for 5 weeks. The cumulative dark and light IOP elevations were 277 +/- 86 and 113 +/- 50 mmHg days respectively while the cumulative total (light and dark) IOP elevation was 213 +/- 114 mmHg days. After 5 weeks, regional RGC body loss of 29.5 +/- 15.5% and moderate axonal injury were observed. Axonal injury and loss of RGC body had a high correlation with the cumulative total IOP elevation (R-2 = 0.60 and 0.65 respectively). There was an association between the cumulative dark IOP, elevation and RGC body loss (R-2 = 0.37) and axonal injury (R-2 = 0.51) whereas the associations between neuronal damages and the cumulative light IOP, elevation were weak (for RGC body loss, R-2 = 0.01; for axonal injury, R-2 = 0.26). Simple linear regression model analysis showed statistical significance for the relationships between the total cumulative IOP elevation and RGC body loss (P = 0.009), and axonal injury (P = 0.016). To examine the role of light and dark IOP elevation in RGC body loss and axonal injury, analyses for the association between different light/dark IOP factors and percentage of RGC body loss/axonal injury grading were performed and only the association between the cumulative dark IOP elevation and axonal injury showed statistical significance (P = 0.033). The findings demonstrated that the cumulative total (light and dark) IOP elevation is a risk factor to RGC degeneration in a rat model of experimental glaucoma using modified partial laser photocoagulation at 330 degrees trabecular meshwork. Further investigations are required to understand the role of longer term light and dark phase IOP elevation contributing to the progression of degeneration in different compartments of RGCs. (C) 2013 Elsevier Ltd. All rights reserved.