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Publication : Physiological Effects of Soat1 Inactivation on Homeostasis of the Mouse Ocular Surface.

First Author  Wilkerson A Year  2024
Journal  Invest Ophthalmol Vis Sci Volume  65
Issue  8 Pages  2
PubMed ID  38953847 Mgi Jnum  J:360325
Mgi Id  MGI:7663487 Doi  10.1167/iovs.65.8.2
Citation  Wilkerson A, et al. (2024) Physiological Effects of Soat1 Inactivation on Homeostasis of the Mouse Ocular Surface. Invest Ophthalmol Vis Sci 65(8):2
abstractText  PURPOSE: Soat1/SOAT1 have been previously reported to be critical for the biosynthesis of cholesteryl esters (CEs) in the mouse Meibomian glands (MGs) as the loss of function led to an arrest of CE production and a substantial accumulation of nonesterified cholesterol in the meibum, causing an increase in its melting temperature. The purpose of this study was to further investigate the role of Soat1 in meibogenesis and ocular surface physiology. METHODS: The mouse ocular features of knockout Soat1-/- and wild type (WT) mice were studied using various ophthalmic and histological techniques, mouse lipidomes were monitored using liquid chromatography/mass spectrometry, whereas their transcriptomes were compared to characterize the effects of the mutation on the gene expression profiles in the MG and cornea. RESULTS: Soat1-/- mice displayed increased tear production and severe corneal abnormalities, such as corneal thinning, (neo)vascularization, ulceration, and opacification that progressed with aging. Transcriptomic analyses led to identification of a range of significantly disrupted pathways, which included general and specific lipid metabolism-related pathways, keratinization, angiogenesis/(neo)vascularization, muscle contraction, and several other pathways. In addition, histological and histochemical experiments revealed morphological changes in the MG, cornea, and conjunctiva in Soat1-/- mice. Notably, the mRNA microarray expression level of Soat1 in WT MGs (log2 17.5) was 1000 x of that in the mouse cornea (log2 7.5). CONCLUSIONS: These findings suggest a direct involvement of Soat1/SOAT1 in MGs in maintaining ocular surface homeostasis, in general, and corneal health, specifically.
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