Investigative ophthalmology & visual science · 2025
Degradation of Elastic Fiber Triggers Lacrimal Gland Dysfunction in Marfan Syndrome Mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Xiao Bing, Hu Leyi, Zhang Xinyu, Liu Liyan, Young Charlotte, Liu Xinxin, Ye Qian, Zheng Danying, Liang Lingyi, Jin Guangming
Аннотация
PURPOSE: Elastic fibers constitute essential elements of the extracellular matrix (ECM) in the lacrimal gland (LG), yet their influence on tear secretion is not fully elucidated. This study examined the impact of elastic fibers on LG secretory function in a Marfan syndrome (MFS) mouse model, characterized by inherent elastic fiber defects.
METHODS: Alterations of the ocular surface in female MFS mice along with their control strains were assessed using a phenol red test for tear production and fluorescein staining for corneal integrity. The LGs were harvested and processed for histology, immunohistochemistry, transcriptional profiling, and Western blotting.
RESULTS: MFS mice exhibited reduced tear production and corneal epithelial defects. Morphologically, a yellow-brown appearance was observed, along with vacuole formation, atrophied acini with dense collagen deposition, and increased infiltration of inflammatory cells in the LG. Furthermore, a decrease in elastic fiber integrity, accompanied by collagen fiber accumulation within the ECM of LG, was noted. Additionally, decreased expression of vesicle-trafficking GTPase (Rab3D) and α<@150>smooth muscle actin in the acini of MFS mice was associated with impaired lacrimal secretion. Notably, TGF-β signaling was activated in the LG of MFS mice. RNA sequencing analysis revealed immune activation and ECM dysfunction as core pathological features.
CONCLUSIONS: Abnormalities of elastic fibers in LG ECM due to fibrillin-1 deficiency can lead to inflammatory and fibrotic disorders and ultimately LG dysfunction.
METHODS: Alterations of the ocular surface in female MFS mice along with their control strains were assessed using a phenol red test for tear production and fluorescein staining for corneal integrity. The LGs were harvested and processed for histology, immunohistochemistry, transcriptional profiling, and Western blotting.
RESULTS: MFS mice exhibited reduced tear production and corneal epithelial defects. Morphologically, a yellow-brown appearance was observed, along with vacuole formation, atrophied acini with dense collagen deposition, and increased infiltration of inflammatory cells in the LG. Furthermore, a decrease in elastic fiber integrity, accompanied by collagen fiber accumulation within the ECM of LG, was noted. Additionally, decreased expression of vesicle-trafficking GTPase (Rab3D) and α<@150>smooth muscle actin in the acini of MFS mice was associated with impaired lacrimal secretion. Notably, TGF-β signaling was activated in the LG of MFS mice. RNA sequencing analysis revealed immune activation and ECM dysfunction as core pathological features.
CONCLUSIONS: Abnormalities of elastic fibers in LG ECM due to fibrillin-1 deficiency can lead to inflammatory and fibrotic disorders and ultimately LG dysfunction.