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Chuanqing Ding, Mate Katona, Eszter Vizvari, Orsolya Berczeli, Andrea Facsko, Zoltan Rakonczay Jr, Peter Hegyi, Edit Toth-Molnar; Structural and functional changes of lacrimal gland functional unit in CFTR knockout mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):430.
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© ARVO (1962-2015); The Authors (2016-present)
Lacrimal gland (LG) is the major source of tears, which is mediated by an array of ion transporters/channels. Cystic fibrosis transmembrane conductance regulator (CFTR) plays a critical role in many exocrine glands, but its role in LG secretion is unknown. Availability of transgenic mouse models carrying genetic defects in CFTR allows direct examination of the role of CFTR in LG secretion, and therefore the aim of the present study is to investigate potential structural and functional changes from CFTR knock out (KO) mice, as compared to wild types (WT).
Mice used throughout the studies were based on the congenic FVB/N background. Morphometric assessment of LG was used to evaluate potential changes of morphology in KO mice. Tear production was measured in anesthetized mice using phenol red impregnated cotton threads, and wetting length were measured. Ocular surface integrity was investigated by applying fluorescein sodium into the conjunctival sac, followed by corneal evaluation by a slit lamp biomicroscope equipped with cobalt-blue light, with the staining assessed by using the 2007 Dry Eye WorkShop (DEWS) grading system. The cornea was divided into five regions and staining was assessed and rated in each region from 0 to 4. The total score from the five regions was recorded and analyzed, with p<0.05 was considered statistically significant.
Morphometric assessment of acinar and ductal lumens did not reveal noticeable differences of LG morphology between KO and WT mice, as contrast to what has been suspected before. Tear secretion from mice at 8-10 weeks were 2.36±0.31 mm/5 min (n=7) in WT mice, and 1.28±0.19 mm/5 min (n=11) in KO mice (p=0.0021). In 14-16 weeks group, tear secretion was 4.68±0.69 mm/5 min (n=9) in WT mice and 2.33±0.68 mm/5 min (n=5) in KO mice (p=0.0027). For those mice at 22-24 weeks, tear secretion was 3.35±0.6 mm/5 min (n=7) in the WT group and 1.37±0.08 mm/5 min (n=4) in KO group (p=0.00007). Corneal staining score was 1.5±1.16 in WT mice (n=6) and 9.16±1.83 in KO mice (n=6, p=0.00008) in animals at 8-10 weeks, while in the 22-24 weeks group, the staining was 7.16 ±1.5 in WT mice (n=6) and 15.33±1.66 in KO animals (n=6, p=0.0018).
These data demonstrated significant decreases in tear secretion and defects in ocular surface integrity in KO mice, suggesting the key role CFTR may play in LG secretion and the maintenance of ocular surface integrity.
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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