Intraocular CNTF reduces vision in normal rats in a dose-dependent manner
Intraocular CNTF reduces vision in normal rats in a dose-dependent manner
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DOI：
10.1167/iovs.07-0054
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发表时间：
2007-12-01
影响因子：
4.4
通讯作者：
LaVail, Matthew M.
中科院分区：
文献类型：
--
作者：
McGill, Trevor J.;Prusky, Glen T.;LaVail, Matthew M.
目的。CNTF是一种视网膜退行性变的神经保护剂，可导致视网膜电信号(ERG)幅度降低。本研究的目的是确定眼内注射CNTF对正常大鼠视功能的影响。方法：在单眼玻璃体内注射CNTF或视网膜下注射腺相关病毒载体CNTF(AAV-CNTF)前后，测量成年Long-Evans大鼠视动力学反应(OKR)的全视野暗视和明视ERG幅值和空间频率阈值。在注射AAV-CNTF的动物中，也使用视觉水任务来测量视力。结果：注射大剂量CNTF后，大鼠上丘ERG波幅和OKR阈值在注射后6d内下降45%~70%。ERG波幅在21天时开始恢复，而OKR阈值在56天后才开始恢复。OKR阈值和ERG波幅直到90~100天才完全恢复。在注射CNTF后2周测量上丘的亮度阈值提高了0.35个对数单位。在注射AAV-CNTF的眼睛中，OKR阈值和视力在至少6个月内下降了约50%，暗视和明视ERGb波下降了30%到50%。部分眼的注入区出现光感受器丧失。相比之下，剂量-反应分析与光损伤的剂量-反应研究的比较有力地表明，治疗剂量的CNTF并不抑制ERG反应。结论：眼内给药CNTF保留了视网膜变性动物模型中的光感受器，在非常高的剂量下损害了正常大鼠的视觉功能，但在低剂量下不会对持续的光损伤提供保护。
PURPOSE. CNTF is a neuroprotective agent for retinal degenerations that can cause reduced electroretinogram ( ERG) amplitudes. The goal of the present study was to determine the effects of intraocular delivery of CNTF on normal rat visual function.METHODS. Full-field scotopic and photopic ERG amplitudes and spatial frequency thresholds of the optokinetic response (OKR) of adult Long-Evans rats were measured before and after intravitreous injection of CNTF or subretinal delivery of adenoassociated virus-vectored CNTF (AAV-CNTF) into one eye. Visual acuity was also measured by using the Visual Water Task in AAV-CNTF-injected animals. Multiunit luminance thresholds were recorded in the superior colliculus after CNTF injection, and the eyes were examined histologically.RESULTS. In eyes injected with a high dose of CNTF, ERG amplitudes and OKR thresholds measured through CNTF-injected eyes were decreased by 45% to 70% within 6 days after injection. ERG amplitudes had begun to recover by 21 days, whereas OKR thresholds only began to recover after 56 days. Neither OKR thresholds nor ERG amplitudes fully recovered until 90 to 100 days. When measured in the superior colliculus at 2 weeks after CNTF injection, luminance thresholds were elevated by 0.35 log units. In AAV-CNTF-injected eyes, OKR thresholds, and visual acuity were reduced by approximately 50% for at least 6 months, and scotopic and photopic ERG b-waves were reduced by 30% to 50%. Photoreceptor loss occurred in the injected regions in some of the eyes. By contrast, comparison of dose - response analysis with a dose response study of light damage strongly suggests that therapeutic doses of CNTF exist that do not suppress ERG responses.CONCLUSIONS. Intraocular delivery of CNTF, which preserves photoreceptors in animal models of retinal degeneration, impairs visual function in normal rats at very high doses, but not at lower doses that still provide protection from constant light damage.