Department of Ophthalmology and Visual Sciences, John Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Invest Ophthalmol Vis Sci. 2011 Aug 29;52(9):6766-73. doi: 10.1167/iovs.10-7147.
The optomotor reflex of DBA/2J (D2), DBA/2J-Gpnmb+ (D2-Gpnmb+), and C57BL/6J (B6) mouse strains was assayed, and the retinal ganglion cell (RGC) firing patterns, direction selectivity, vestibulomotor function and central vision was compared between the D2 and B6 mouse lines.
Intraocular pressure (IOP) measurements, real-time PCR, and immunohistochemical analysis were used to assess the time course of glaucomatous changes in D2 retinas. Behavioral analyses of optomotor head-turning reflex, visible platform Morris water maze and Rotarod measurements were conducted to test vision and vestibulomotor function. Electroretinogram (ERG) measurements were used to assay outer retinal function. The multielectrode array (MEA) technique was used to characterize RGC spiking and direction selectivity in D2 and B6 retinas.
Progressive increase in IOP and loss of Brn3a signals in D2 animals were consistent with glaucoma progression starting after 6 months of age. D2 mice showed no response to visual stimulation that evoked robust optomotor responses in B6 mice at any age after eye opening. Spatial frequency threshold was also not measurable in the D2-Gpnmb+ strain control. ERG a- and b-waves, central vision, vestibulomotor function, the spiking properties of ON, OFF, ON-OFF, and direction-selective RGCs were normal in young D2 mice.
The D2 strain is characterized by a lack of optomotor reflex before IOP elevation and RGC degeneration are observed. This behavioral deficit is D2 strain-specific, but is independent of retinal function and glaucoma. Caution is advised when using the optomotor reflex to follow glaucoma progression in D2 mice.
检测 DBA/2J(D2)、DBA/2J-Gpnmb+(D2-Gpnmb+)和 C57BL/6J(B6)小鼠品系的光感受器运动反射,并比较 D2 和 B6 小鼠系之间的视网膜神经节细胞(RGC)放电模式、方向选择性、前庭运动功能和中央视力。
通过眼压(IOP)测量、实时 PCR 和免疫组织化学分析,评估 D2 视网膜青光眼变化的时程。通过光感受器转头反射、可见平台 Morris 水迷宫和转棒测量进行行为分析,以测试视力和前庭运动功能。通过视网膜电图(ERG)测量,评估外视网膜功能。多电极阵列(MEA)技术用于表征 D2 和 B6 视网膜中的 RGC 放电和方向选择性。
D2 动物的 IOP 逐渐升高和 Brn3a 信号丢失与 6 个月龄后开始的青光眼进展一致。D2 小鼠在任何年龄都没有对视觉刺激产生反应,而 B6 小鼠在睁眼后任何年龄对视觉刺激都会产生强烈的光感受器运动反应。在 D2-Gpnmb+ 品系对照中,也无法测量空间频率阈值。在年轻的 D2 小鼠中,ERG a-和 b-波、中央视力、前庭运动功能、ON、OFF、ON-OFF 和方向选择性 RGC 的放电特性均正常。
在观察到眼压升高和 RGC 变性之前,D2 品系的特征是缺乏光感受器运动反射。这种行为缺陷是 D2 品系特有的,但与视网膜功能和青光眼无关。在使用光感受器运动反射来跟踪 D2 小鼠的青光眼进展时,应谨慎行事。