ArticleInvestigative ophthalmology & visual science2025
Degradation of Elastic Fiber Triggers Lacrimal Gland Dysfunction in Marfan Syndrome Mice.
Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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