Ben-Shlomo Gil, Bakalash Sharon, Lambrou George N, Latour Elisabeth, Dawson William W, Schwartz Michal, Ofri Ron
Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Herzl Street, P.O. Box 12, Rehovot 76100, Israel.
Exp Eye Res. 2005 Sep;81(3):340-9. doi: 10.1016/j.exer.2005.02.006.
With the increasing use of the rat as an animal model for glaucoma and for the evaluation of neuroprotective treatments, there is a need for a sensitive test of retinal ganglion cell (RGC) function in this species. The aims of this study were to detect functional abnormalities of the inner retina in a rat model of high intraocular pressure (IOP) using the pattern electroretinogram (PERG), and to correlate them with morphometric analysis of RGC survival and the functional integrity of the inner retina. Unilateral ocular hypertension was induced in 17 Lewis rats through laser photocoagulation. Pattern ERGs were recorded prior to lasering and 3 weeks later, using a series of shifting patterns of decreasing spatial frequency projected directly onto the animals' fundus. IOP was measured at the same intervals, and the number of surviving RGCs estimated. Low amplitude PERG signals could be recorded in response to a narrow grating of 0.368 cycles per degree (cpd), and increased with stimulus size. Lasering caused mean (+/-s.d.) IOP to increase significantly from 18.3+/-4.5 (baseline) to 29.8+/-8.8 mmHg within 3 weeks (p<0.0001). At this time, PERG amplitudes were significantly reduced (p<0.05), declining an average of 45% compared to the normotensive, control eyes. No outer retinal damage was observed, but the mean number of RGCs decreased significantly (p<0.001), from 2 525.0+/-372.4 to 1 542.8+/-333.8 cells per mm2. This decrease in RGC number was significantly (p=0.03) correlated the decrease in PERG amplitude. The correlation between functional integrity of the inner retina and the rat PERG was further demonstrated by intravitreal tetrodotoxin injections, which temporarily abolished the PERG but did not affect outer retinal activity, reflected in the flash ERG. The evidence for early functional deficits, combined with tonometry and documentation of correlated ganglion cells loss, confirms the sensitivity of this diagnostic tool and the validity and importance of this animal model in glaucoma research.
随着大鼠越来越多地被用作青光眼动物模型以及神经保护治疗评估模型，需要一种针对该物种视网膜神经节细胞（RGC）功能的敏感检测方法。本研究的目的是使用图形视网膜电图（PERG）检测高眼压（IOP）大鼠模型中视网膜内层的功能异常，并将其与RGC存活的形态学分析以及视网膜内层的功能完整性相关联。通过激光光凝在17只Lewis大鼠中诱导单侧高眼压。在激光治疗前和3周后记录图形视网膜电图，使用一系列直接投射到动物眼底的空间频率逐渐降低的移动图形。以相同的时间间隔测量眼压，并估计存活的RGC数量。可以记录到对每度0.368周（cpd）的窄光栅的低幅度PERG信号，并且该信号随刺激大小增加。激光治疗导致平均（±标准差）眼压在3周内从18.3±4.5（基线）显著增加到29.8±8.8 mmHg（p<0.0001）。此时，PERG振幅显著降低（p<0.05），与正常眼压的对照眼相比平均下降45%。未观察到视网膜外层损伤，但RGC的平均数量显著减少（p<0.001），从每平方毫米2525.0±372.4个细胞降至1542.8±333.8个细胞。RGC数量的减少与PERG振幅的降低显著相关（p=0.03）。玻璃体内注射河豚毒素进一步证明了视网膜内层功能完整性与大鼠PERG之间的相关性，该注射暂时消除了PERG，但不影响闪光视网膜电图所反映的视网膜外层活动。早期功能缺陷的证据，结合眼压测量和相关神经节细胞丢失的记录，证实了该诊断工具的敏感性以及该动物模型在青光眼研究中的有效性和重要性。
