Transgenic C57BL/6 mice expressing human myocilin (Tg-MYOC) are a well-established model for primary open-angle glaucoma (POAG). While the reduced trabecular meshwork (TM) cellularity due to severe endoplasmic reticulum (ER) stress has been characterized as the etiology of this model, there is a limited understanding of how glaucomatous phenotypes evolve over the lifespan of Tg-Myoc mice. In this study, we compiled the model's intraocular pressure (IOP) data recorded in our laboratory from 2017 to 2023 and selected representative eyes to measure the outflow facility (C), a critical parameter indicating the condition of the conventional TM pathway. We found that Tg-MYOC mice aged 4−12 months exhibited significantly higher IOPs than age-matched C57BL/6 mice. Notably, a decline in IOP was observed in Tg-MYOC mice at 17−24 months of age, a phenomenon not attributable to the gene dosage of mutant myocilin. Measurements of the C of Tg-MYOC mice indicated that the age-related IOP reduction was not a result of ongoing TM damage. Instead, Hematoxylin and Eosin staining, immunohistochemistry analysis, and transmission electron microscopic examination revealed that this reduction might be induced by degenerations of the non-pigmented epithelium in the ciliary body of aged Tg-MYOC mice. Overall, our findings provide a comprehensive profile of mutant myocilin-induced ocular changes over the Tg-MYOC mouse lifespan and suggest a specific temporal window of elevated IOP that may be ideal for experimental purposes.

中文翻译：

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Tg-MYOCY437H 小鼠整个生命周期的眼压

表达人肌纤蛋白 (Tg-MYOC) 的转基因 C57BL/6 小鼠是原发性开角型青光眼 (POAG) 的成熟模型。虽然严重内质网 (ER) 应激导致的小梁网 (TM) 细胞结构减少已被定性为该模型的病因，但对于青光眼表型在 Tg-Myoc 小鼠的整个生命周期中如何演变的了解有限。在本研究中，我们整理了2017年至2023年在我们实验室记录的模型眼内压（IOP）数据，并选择代表性眼睛来测量流出设施（C），这是指示传统TM通路状况的关键参数。我们发现 4−12 个月大的 Tg-MYOC 小鼠的 IOP 明显高于年龄匹配的 C57BL/6 小鼠。值得注意的是，在 17-24 月龄的 Tg-MYOC 小鼠中观察到 IOP 下降，这种现象与突变肌纤蛋白的基因剂量无关。 Tg-MYOC 小鼠的 C 测量表明，与年龄相关的 IOP 降低并不是持续 TM 损伤的结果。相反，苏木精和伊红染色、免疫组织化学分析和透射电子显微镜检查表明，这种减少可能是由老年 Tg-MYOC 小鼠睫状体内非色素上皮的变性引起的。总体而言，我们的研究结果提供了 Tg-MYOC 小鼠寿命期间突变肌纤蛋白诱导的眼部变化的全面概况，并提出了一个可能适合实验目的的升高 IOP 的特定时间窗口。