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Dhruva Bhattacharya, Mingwu Wang; Increased Muc5ac Expression in Rabbits with Bilateral Excision of the Main Lacrimal Gland. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5659.
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© ARVO (1962-2015); The Authors (2016-present)
Using a rabbit model in which the entire conjunctiva surface is well preserved, alteration in the expression of goblet cell secreted Muc5ac mucin was investigated in response to an acute dry eye (DE) condition.
A mixed-mechanism DE model was created by excision of nictitating membrane, Harderian gland and main lacrimal gland (LG) in rabbits. Clinical assessment of DE phenotype and Schirmer test were performed before (BE) and monthly for 3 months after excision (AE). Conjunctival impression cytology was obtained at each time point for the extraction of total protein and RNA. Protein levels of inflammatory DE markers (interleukin 1β: IL-1β, and tumor necrosis factor: TNF-α) were quantified by western blots. The expression of Muc5ac and aquaporin (AQP) 5 at mRNA and protein levels were monitored as well in the similar time frame.
Clinical DE phenotype in rabbits was observed at 1-month AE, which was corroborated by increased expression of biomarkers (TNF-α, P = 0.0181; IL-1β, P = 0.33). Tear secretion was not decreased AE and the DE phenotype spontaneous improved over 3 months AE to near baseline (BE). The Muc5ac and AQP5 expression followed a similar trend and were found to progressively increase at 1- and 2-month AE, and return to baseline (BE) level by 3-months AE. This was in synchrony with the clinical DE phenotype and levels of inflammatory biomarkers. Our Muc5ac result is contrary to the previous findings in studies of human and animal DE models.
Spontaneous improvement of DE phenotype in this rabbit model is potentially due to conjunctival AQP5 mediated compensatory tear fluid balance. Up regulation of AQP5 further leads to the increased expression of Muc5ac. Altogether, conjunctiva potentially has an inherent defense machinery to combat external insults, at least in an acute setting.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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