Departments of Integrative Medical Biology, Section for Anatomy, Neurology, Umeå University, Umeå, Sweden.
Invest Ophthalmol Vis Sci. 2010 Jul;51(7):3494-501. doi: 10.1167/iovs.09-5030. Epub 2010 Feb 24.
PURPOSE. To investigate the general morphology, fiber type content, and myosin heavy chain (MyHC) composition of extraocular muscles (EOMs) from postmortem donors with amyotrophic lateral sclerosis (ALS) and to evaluate whether EOMs are affected or truly spared in this disease. METHODS. EOM and limb muscle samples obtained at autopsy from ALS donors and EOM samples from four control donors were processed for immunohistochemistry with monoclonal antibodies against distinct MyHC isoforms and analyzed by SDS-PAGE. In addition, hematoxylin and eosin staining and nicotinamide tetrazolium reductase (NADH-TR) activity were studied. RESULTS. Wide heterogeneity was observed in the appearance of the different EOMs from each single donor and between donors, irrespective of ALS type or onset. Pathologic morphologic findings in ALS EOMs included presence of atrophic and hypertrophic fibers, either clustered in groups or scattered; increased amounts of connective tissue; and areas of fatty replacement. The population of fibers stained with anti-MyHCslow tonic was smaller than that of MyHCIpositive fibers and was mostly located in the orbital layer in most of the ALS EOM samples, whereas an identical staining pattern for both fiber populations was observed in the control specimens. MyHCembryonic was notably absent from the ALS EOMs. CONCLUSIONS. The EOMs showed signs of involvement with altered fiber type composition, contractile protein content, and cellular architecture. However, when compared to the limb muscles, the EOMs were remarkably preserved. EOMs are a useful model for the study of the pathophysiology of ALS.
目的。研究肌萎缩侧索硬化症（ALS）死后供体的眼外肌（EOM）的一般形态、纤维类型含量和肌球蛋白重链（MyHC）组成，并评估 EOM 是否受到影响或在该疾病中真正不受影响。
方法。从 ALS 供体尸检中获得 EOM 和肢体肌肉样本，以及来自 4 个对照供体的 EOM 样本，用针对不同 MyHC 同工型的单克隆抗体进行免疫组织化学处理，并通过 SDS-PAGE 进行分析。此外，还进行了苏木精和伊红染色以及烟酰胺腺嘌呤二核苷酸脱氢酶（NADH-TR）活性研究。
结果。无论 ALS 类型或发病时间如何，每个供体的不同 EOM 之间以及供体之间观察到明显的异质性。ALS EOM 中的病理性形态学发现包括存在萎缩和肥大纤维，无论是成簇存在还是散在存在；结缔组织增多；和脂肪替代区域。用抗 MyHCslow 肌球蛋白染色的纤维数量少于 MyHCI 阳性纤维，并且在大多数 ALS EOM 样本中主要位于眶层，而在对照标本中观察到两种纤维群的相同染色模式。ALS EOM 中明显缺乏 MyHC 胚胎型。
结论。EOM 表现出受累迹象，纤维类型组成、收缩蛋白含量和细胞结构发生改变。然而，与肢体肌肉相比，EOM 保存得非常完好。EOM 是研究 ALS 病理生理学的有用模型。
