Selective ganglion cell functional loss in rats with experimental glaucoma
Selective ganglion cell functional loss in rats with experimental glaucoma
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DOI：
10.1167/iovs.03-1411
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发表时间：
2004-06-01
影响因子：
4.4
通讯作者：
Cioffi, GA
中科院分区：
文献类型：
--
作者：
Fortune, B;Bui, BV;Cioffi, GA
目的.目的：研究高眼压对大鼠视网膜功能的影响。在20只成年雄性Brown-Norway大鼠中，通过向巩膜外静脉注射高渗盐水，造成单侧IOP升高。每周4 - 5次测量清醒动物双眼的IOP。5周后，使动物暗适应过夜（>12小时），并同时从双眼获得全视野视网膜电图（ERGS）。暗视ERG刺激为短暂的白色闪光（-6.64-2.72 log cd-s/m（2））。在150 cd/m2的光适应15分钟后，也获得了明视反应（0.97-2.72 log cd-s/m2）。第二天对眼睛进行处理，通过光学显微镜进行组织学评价，包括掩蔽确定视神经损伤等级（ONIG; 1，正常; 5，严重，弥漫性损伤）。在实验眼中，组平均IOP（+/-SD）为34.5 +/- 4.1 mm Hg，而对照眼的平均值为28.1 +/- 0.5 mm Hg（t = 7.1，P < 0.0001）。实验眼和对照眼的平均ONIG分别为3.4 ± 1.7和1.0 ± 0.02（t = 6.3，P < 0.0001）。实验眼ONIG随平均眼压的升高而升高（r（2）= 0.78，P < 0.0001），而对照眼ONIG与平均眼压无相关性（r（2）= 0.09，P = 0.18）。在具有相对轻微的IOP升高（平均IOP < 31 mm Hg）并且通过光学显微镜（ONIG = 1.1 +/- 0.2，n = 5）没有明显的视神经结构（组织学）损伤的实验眼中，存在正暗视阈值反应（pSTR; P < 0.001）的选择性降低，而其他ERG成分保持不变。在五只眼睛中的四只中，pSTR振幅降低超过50%，而所有五只眼睛都具有正常的暗视a波、b波和4振幅。平均眼压大于35 mm Hg的眼a波、b波和振荡电位（OP）振幅降低。如先前的研究所证明的，pSTR的选择性丧失指示选择性视网膜神经节细胞（RGC）损伤。在这种大鼠实验性青光眼模型中，通过光学显微镜观察视神经组织，发现选择性RGC功能损伤发生在结构损伤发生之前。最高IOP水平导致非选择性功能丧失。因此，在实验性青光眼的啮齿动物模型中，较低水平的慢性升高的IOP可能与人类原发性慢性青光眼更相关。
PURPOSE. To characterize retinal functional consequences of elevated intraocular pressure (IOP) in a rat model of experimental glaucoma.METHODS. Unilateral elevation of IOP was produced by hypertonic saline injection into an episcleral vein in 20 adult male Brown-Norway rats. IOP was measured in both eyes of awake animals four to five times per week. After 5 weeks, animals were dark adapted overnight (>12 hours) and full-field electroretinograms (ERGS) were obtained simultaneously from both eyes. Scotopic ERG stimuli were brief white flashes (-6.64-2.72 log cd-s/m(2)). Photopic responses were also obtained (0.97-2.72 log cd-s/m(2)) after 15 minutes of light adaptation (150 cd/m(2)). Eyes were processed the following day for histologic evaluation by light microscopy, including masked determination of optic nerve injury grade (ONIG; 1, normal; 5, severe, diffuse damage).RESULTS. Among experimental eyes, the group average IOP (+/-SD) was 34.5 +/- 4.1 mm Hg, whereas the average for control eyes was 28.1 +/- 0.5 mm Hg (t = 7.1, P < 0.0001). The average ONIG for experimental and control eye groups, respectively, was 3.4 ± 1.7 and 1.0 ± 0.02 (t = 6.3, P < 0.0001). The ONIG increased with mean IOP in experimental eyes (r(2) = 0.78, P < 0.0001) and was unrelated to mean IOP in control eyes (r2 = 0.09, P = 0.18). In experimental eyes with relatively mild IOP elevation (mean IOP < 31 mm Hg) and no structural (histologic) damage to the optic nerve evident by light microscopy (ONIG = 1.1 +/- 0.2, n = 5), there was a selective reduction of the positive scotopic threshold response (pSTR; P < 0.001), whereas other ERG components remained unaltered. In four of the five eyes, pSTR amplitude was reduced by more than 50% whereas all five had normal scotopic a-wave, b-wave, and 4 amplitudes. Eyes with mean IOP of more than 35 mm Hg had reduced a-wave, b-wave, and oscillatory potential (OP) amplitudes.CONCLUSIONS. As demonstrated by prior studies, selective loss of the pSTR is indicative of selective retinal ganglion cell (RGC) injury. In this rat model of experimental glaucoma, selective RGC functional injury occurred before the onset of structural damage, as assessed by light microscopy of optic nerve tissue. The highest IOP levels resulted in nonselective functional loss. Thus, in rodent models of experimental glaucoma, lower levels of chronically elevated IOP may be more relevant to human primary chronic glaucoma.