McMullen Colleen A, Andrade Francisco H, Stahl John S
Department of Neurology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA.
J Neurosci. 2004 Jan 7;24(1):161-9. doi: 10.1523/JNEUROSCI.3234-03.2004.
Previous studies have suggested that abnormal visual experience early in life induces ocular motor abnormalities. The purpose of this study was to determine how visual deprivation alters the function and gene expression profile of the ocular motor system in mice. We measured the effect of dark rearing on eye movements, gene expression in the oculomotor nucleus, and contractility of isolated extraocular muscles. In vivo eye movement recordings showed decreased gains for optokinetic and vestibulo-ocular reflexes, confirming an effect of dark rearing on overall ocular motor function. Saccade peak velocities were preserved, however, arguing that the quantitative changes in these reflexes were not secondary to limitations in force generation. Using microarrays and quantitative PCR, we found that dark rearing shifted the oculomotor nucleus transcriptome to a state of delayed/arrested development. The expression of 132 genes was altered by dark rearing; these genes fit in various functional categories (signal transduction, transcription/translation control, metabolism, synaptic function, cytoskeleton), and some were known to be associated with neuronal development and plasticity. Extraocular muscle contractility was impaired by dark rearing to a greater extent than expected from the in vivo ocular motility studies: changes included decreased force and shortening speed and evidence of abnormal excitability. The results indicate that normal development of the mouse ocular motor system and its muscles requires visual experience. The transcriptional pattern of arrested development may indicate that vision is required to establish the adult pattern, but it also may represent the plastic response of oculomotor nuclei to abnormal extraocular muscles.
以往的研究表明，生命早期异常的视觉体验会诱发眼球运动异常。本研究的目的是确定视觉剥夺如何改变小鼠眼球运动系统的功能和基因表达谱。我们测量了暗饲养对眼动、动眼神经核基因表达以及离体眼外肌收缩性的影响。体内眼动记录显示视动性眼反射和前庭眼反射的增益降低，证实了暗饲养对整体眼球运动功能的影响。然而，扫视峰值速度保持不变，这表明这些反射的定量变化并非继发于力量产生的限制。使用微阵列和定量PCR，我们发现暗饲养使动眼神经核转录组转变为延迟/停滞发育状态。132个基因的表达因暗饲养而改变；这些基因属于各种功能类别（信号转导、转录/翻译控制、代谢、突触功能、细胞骨架），其中一些已知与神经元发育和可塑性有关。与体内眼球运动研究预期相比，暗饲养对眼外肌收缩性的损害更大：变化包括力量和缩短速度降低以及异常兴奋性的证据。结果表明，小鼠眼球运动系统及其肌肉的正常发育需要视觉体验。发育停滞的转录模式可能表明需要视觉来建立成年模式，但它也可能代表动眼神经核对外眼肌异常的可塑性反应。
