Willoughby Christy L, Fleuriet Jérome, Walton Mark M, Mustari Michael J, McLoon Linda K
Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, United States 2Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States.
Washington National Primate Research Center, Seattle, Washington, United States 4Department of Ophthalmology, University of Washington, Seattle, Washington, United States.
Invest Ophthalmol Vis Sci. 2015 Jun;56(6):3467-83. doi: 10.1167/iovs.15-16852.
We evaluated promising new treatment options for strabismus. Neurotrophic factors have emerged as a potential treatment for oculomotor disorders because of diverse roles in signaling to muscles and motor neurons. Unilateral treatment with sustained release brain-derived neurotrophic factor (BDNF) to a single lateral rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop in correlation with extraocular muscle (EOM) changes during the critical period for development of binocularity.
The lateral rectus muscles of one eye in two infant macaques were treated with sustained delivery of BDNF for 3 months. Eye alignment was assessed using standard photographic methods. Muscle specimens were analyzed to examine the effects of BDNF on the density, morphology, and size of neuromuscular junctions, as well as myofiber size. Counts were compared to age-matched controls.
No change in eye alignment occurred with BDNF treatment. Compared to control muscle, neuromuscular junctions on myofibers expressing slow myosins had a larger area. Myofibers expressing slow myosin had larger diameters, and the percentage of myofibers expressing slow myosins increased in the proximal end of the muscle. Expression of BDNF was examined in control EOM, and observed to have strongest immunoreactivity outside the endplate zone.
We hypothesize that the oculomotor system adapted to sustained BDNF treatment to preserve normal alignment. Our results suggest that BDNF treatment preferentially altered myofibers expressing slow myosins. This implicates BDNF signaling as influencing the slow twitch properties of EOM.
我们评估了斜视有前景的新治疗方案。神经营养因子已成为动眼神经疾病的一种潜在治疗方法，因为它们在向肌肉和运动神经元发出信号方面具有多种作用。对幼年猴子的单条外直肌进行持续释放脑源性神经营养因子（BDNF）的单侧治疗，以检验在双眼视觉发育关键期斜视是否会与眼外肌（EOM）变化相关发展的假设。
对两只幼年猕猴一只眼睛的外直肌进行持续3个月的BDNF给药治疗。使用标准摄影方法评估眼位。分析肌肉标本，以检查BDNF对神经肌肉接头的密度、形态和大小以及肌纤维大小的影响。将计数结果与年龄匹配的对照组进行比较。
BDNF治疗后眼位未发生变化。与对照肌肉相比，表达慢肌球蛋白的肌纤维上的神经肌肉接头面积更大。表达慢肌球蛋白的肌纤维直径更大，且在肌肉近端表达慢肌球蛋白的肌纤维百分比增加。在对照EOM中检测了BDNF的表达，观察到终板区外具有最强的免疫反应性。
我们假设动眼系统适应了持续的BDNF治疗以保持正常眼位。我们的结果表明，BDNF治疗优先改变了表达慢肌球蛋白的肌纤维。这意味着BDNF信号传导影响EOM的慢收缩特性。
