A new mouse model of inducible, chronic retinal ganglion cell dysfunction not associated with cell death.
A new mouse model of inducible, chronic retinal ganglion cell dysfunction not associated with cell death.
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一种新的诱导性慢性视网膜神经节细胞功能障碍小鼠模型，与细胞死亡无关。
DOI：
10.1167/iovs.12-11375
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发表时间：
2013
影响因子：
4.4
通讯作者：
Porciatti,Vittorio
中科院分区：
文献类型：
--
作者：
Yang,Xu;Chou,Tsung-Han;Ruggeri,Marco;Porciatti,Vittorio
目的：开发与细胞死亡无关的诱导性慢性视网膜神经节细胞 (RGC) 功能障碍的小鼠模型。方法：在对侧上丘 (SC) 抽吸之前和之后，对 18 只 C57BL/6J 小鼠进行纵向模式视网膜电图 (PERG) 和谱域光学相干断层扫描 (OCT) 测试，抽吸对侧上丘 (SC)，去除视束轴突末端和 SC 的浅层。在 4 个月的终点，采集视网膜进行 Brn3b 免疫染色和 BDNF 免疫印迹。结果：PERG 在损伤后第一天内损失了约 60% 的基线幅度（P<0.01），并在 4 个月内保持在降低的水平。终点时，Brn3b阳性RGC密度正常，但细胞核大小减少约24%（P<001）。 OCT 测量显示，从病变后 10 至 20 天开始，内侧视网膜（而非外侧）变薄约 9%（P<0.01）。视网膜神经纤维层厚度没有变化。在终点时，视网膜匀浆显示 BDNF 蛋白水平显着过度表达。结论：成年小鼠的机械性 SC 损伤会导致 RGC 电反应性快速、慢性丧失，随后出现细胞收缩，但不会导致细胞死亡。 SC损伤小鼠代表了一种新的诱导模型，可以研究RGC功能障碍的阶段和机制，而不会受到现有视神经病变和视神经损伤模型中常见的细胞死亡的混杂影响。
Purpose.: To develop a mouse model of inducible, chronic retinal ganglion cell (RGC) dysfunction not associated with cell death.Methods.: Eighteen C57BL/6J mice were longitudinally tested with pattern electroretinogram (PERG) and spectral-domain optical coherence tomography (OCT) before and after aspiration of the contralateral superior colliculus (SC), which removed terminals of optic tract axons and the superficial layers of the SC. At the 4-month end points, retinas were harvested for Brn3b immunostaining and BDNF immunoblotting.Results.: The PERG lost approximately 60% of its baseline amplitude (P< 0.01) within the first day after lesion, and remained at a reduced level over 4 months. At the end point, the density of Brn3b-positive RGCs was normal, but their nucleus size was reduced by approximately 24%(P< 001). OCT measurements showed thinning of the inner, but not outer, retina by approximately 9%(P< 0.01) starting 10 to 20 days after lesion. Retinal nerve fiber layer thickness was unchanged. At the end point, retinal homogenates showed a substantial overexpression of BDNF protein level.Conclusions.: Mechanical SC lesion in adult mice results in a rapid, chronic loss of RGC electrical responsiveness that is followed by cell shrinkage but not cell death. The SC-lesion mouse represents a new, inducible model that allows investigating stages and mechanisms of RGC dysfunction without the confounding effects of cell death that are common in the existing models of optic neuropathies and optic nerve lesions.