Neural Adaptation to Strabismus Surgery

描述（由申请人提供）：虽然手术矫正通常是斜视的首选治疗方法，但其结果可能存在问题。据报道，20-40%的斜视矫正手术以这样或那样的方式失败，因此需要再次手术。我们认为斜视手术有时失败的一个原因是治疗后的适应性过程可能会消除手术的影响，使眼睛恢复到先前的不对准状态。这些适应性过程可能局限于肌肉本身（肌肉重塑），也可能涉及神经过程（中枢神经系统重塑）。该项目的目的是为了更好地了解斜视矫正手术后的神经适应性变化，从而为治疗失败或成功的原因提供更多的见解。我们实验室的研究表明，在双目视觉受损的条件下，特殊饲养的幼猴会再现一种感觉性斜视综合征，包括严重的水平错位、a /V模式、游离水平偏差（DHD）和游离垂直偏差（DVD）。我们的研究策略是首先通过记录眼动核和外展核的运动神经元来表征斜视猴水平眼外肌（内直肌和外直肌）的神经驱动。此后，我们将使用与人类患者相似的切除或退行手术技术治疗这些动物的斜视。治疗后，我们将记录同一运动核的神经反应。比较术前和术后人群对水平眼外肌的神经驱动将提供大脑如何适应肌肉增强或减弱过程的数据。在最后的目的中，我们将记录眼动上区的细胞，以检查手术治疗后的神经适应是否起源于收敛回路。本研究的完成将有助于理解和治疗发育型斜视。

DESCRIPTION (provided by applicant): Although surgical correction is often the preferred treatment method for strabismus, there can be problems with the outcome. By some accounts, 20-40% of strabismus correction surgeries fail in one way or another and therefore re-operation is required. We suggest that a reason strabismus surgery sometimes fails is that there are adaptive processes that follow the treatment that may work to negate the effects of surgery and revert the eyes to a previous state of misalignment. These adaptive processes might be localized to muscle itself (muscle remodeling) or might involve neural processes (central nervous system remodeling). The goal of this project is to develop a better understanding of the neural adaptive changes that follow strabismus correction surgery which in turn may provide additional insight into reasons for failure or success following treatment. Studies from our laboratory have shown that specially rearing infant monkeys under conditions that disrupted binocular vision reproduced a sensory strabismus syndrome with large horizontal misalignment, A/V patterns, Dissociated Horizontal Deviation (DHD) and Dissociated Vertical Deviation (DVD). Our strategy for this project is first to characterize the neural drive to horizontal extraocular muscles (medial and lateral recti) of the strabismic monkeys by recording from motoneurons in the oculomotor and abducens nuclei. Thereafter, we will treat the strabismus in these animals using similar resection or recession surgery techniques to those used in human patients. Following treatment, we will record neural responses from the same motor nuclei. Comparison of the pre- and post-surgery population neural drive to horizontal extraocular muscles will provide data on how the brain adapts to a muscle strengthening or weakening procedure. In the final aim, we will record from cells in the supraoculomotor area to examine whether the neural adaptation that follows surgical treatments has its origin in vergence circuits. Completion of our studies will be of benefit to the understanding and treatment of developmental forms of strabismus.