Department of Clinical Sciences, Neurosciences, Umeå University, Umeå, Sweden.
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
Invest Ophthalmol Vis Sci. 2023 May 1;64(5):15. doi: 10.1167/iovs.64.5.15.
To investigate changes in myofiber composition in the global layer (GL) and orbital layer (OL) of extraocular muscles (EOMs) from terminal amyotrophic lateral sclerosis (ALS) donors.
Medial recti muscles collected postmortem from spinal-onset ALS, bulbar-onset ALS, and healthy control donors were processed for immunofluorescence with antibodies against myosin heavy chain (MyHC) IIa, MyHCI, MyHCeom, laminin, neurofilaments, synaptophysin, acetylcholine receptor γ-subunit, and α-bungarotoxin.
The proportion of myofibers containing MyHCIIa was significantly smaller and MyHCeom was significantly larger in the GL of spinal-onset ALS and bulbar-onset ALS donors compared to control donors. Changes in the GL were more prominent in the bulbar-onset ALS donors, with a significantly larger proportion of myofibers containing MyHCeom being present compared to spinal-onset ALS donors. There were no significant differences in the myofiber composition in the OL. In the spinal-onset ALS donors, the proportions of myofibers containing MyHCIIa in the GL and MyHCeom in the OL were significantly correlated with the disease duration. Neurofilament and synaptophysin were present at motor endplates of myofibers containing MyHCeom in ALS donors.
The EOMs of terminal ALS donors displayed changes in the fast-type myofiber composition in the GL, with a more pronounced alteration in bulbar-onset ALS donors. Our results align with the worse prognosis and subclinical changes in eye movement function previously observed in bulbar-onset ALS patients and suggest that the myofibers in the OL might be more resistant to the pathological process in ALS.
研究终末期肌萎缩侧索硬化症（ALS）患者眼外肌（EOM）的整体层（GL）和眶层（OL）中的肌纤维组成变化。
从脊髓型 ALS、延髓型 ALS 和健康对照供体死后收集的内直肌，用抗肌球蛋白重链（MyHC）IIa、MyHCI、MyHCeom、层粘连蛋白、神经丝、突触素、乙酰胆碱受体γ亚单位和α-银环蛇毒素的抗体进行免疫荧光处理。
与对照组供体相比，脊髓型 ALS 和延髓型 ALS 供体的 GL 中含有 MyHCIIa 的肌纤维比例明显较小，而含有 MyHCeom 的肌纤维比例明显较大。延髓型 ALS 供体的 GL 变化更为明显，含有 MyHCeom 的肌纤维比例明显大于脊髓型 ALS 供体。OL 中的肌纤维组成没有明显差异。在脊髓型 ALS 供体中，GL 中含有 MyHCIIa 的肌纤维比例和 OL 中含有 MyHCeom 的肌纤维比例与疾病持续时间呈显著相关。在 ALS 供体的肌纤维中，神经丝和突触素存在于含有 MyHCeom 的运动终板上。
终末期 ALS 供体的 EOM 显示 GL 中快型肌纤维组成发生变化，延髓型 ALS 供体的变化更为明显。我们的结果与先前观察到的延髓型 ALS 患者的预后较差和眼运动功能的亚临床变化一致，并表明 OL 中的肌纤维可能对 ALS 中的病理过程更具抵抗力。
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