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Abstract #117898 Published in IGR 24-4
Intraocular pressure across the lifespan of Tg-MYOC mice
Zhang X; Xi G; Xi G; Feng P; Li C; Kuehn MH; Zhu WExperimental Eye Research 2024; 241: 109855
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.
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, 266021, China.
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