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Anne M. Floyd, Lingxiang Zhu, Christopher M. Evans, Burton F. Dickey, Mingwu Wang, Yin Chen; Functional and Structural Changes of the Ocular Surface in Muc5ac-deficient Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2330.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the gene expression profile of gel-forming mucins in humans and mice; and to investigate the alterations of the ocular surface in a Muc5ac mucin gene knock-out mouse model.
Different regions of fresh human cadaver and mouse ocular tissues were isolated and dissected. Total RNA was extracted, and gel-forming mucin gene expression was determined by regular and real-time PCR.To evaluate the impact of Muc5ac on the homeostasis of ocular surface, a Muc5ac knock-out mouse model was subjected to various physiological measurements and compared to its wild-type control. Tear break up time (TBUT), phenol cotton thread tests, and corneal fluorescein staining were evaluated in Muc5ac-deficient (-/-) mice (n = 7 male, 5 female) and age matched wild-type (+/+) mice (n = 6 male), aged 12-16 weeks. The study was conducted in compliance with the Tenets of the Declaration of Helsinki and ARVO statement for the use of animals in Ophthalmic and Visual Research.
Among 5 gel-forming mucin genes, MUC5AC was the most abundantly expressed gel-forming mucin in human ocular tissues, while MUC5B was moderately expressed. The expression of MUC19 was detectable at very low levels and neither MUC2 nor MUC6 were expressed in the ocular tissues. This pattern was consistent between human and mouse tissue.Interestingly, the mean TBUT and tear quantity values in Muc5ac-deficient (-/-) mice were significantly lower, and corneal fluorescein staining scores significantly higher compared to the wild type (+/+) mice. Corneal opacification, varying in location, size and severity, was found in 3 eyes of the Muc5ac-deficient (-/-) mice, with no such finding observed in the wild type (+/+) mice.
Dry eye disease is multifactorial and therefore evaluation of the varying components of the tear film, lacrimal unit and corneal structure will contribute to the understanding of dry eye conditions. Our initial results suggest a decline in the quality of tear fluid in the Muc5ac-deficient mice compared to the wild type. Muc5ac knock-out mice have clinical features of dry eye, suggesting such mouse models are potentially useful for studying the pathophysiological changes of the ocular surface when certain mucins are deficient.
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