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V. I. Lossen, S. Samudre, J. Sheppard, Jr., R. L. McKown, G. W. Laurie, P. B. Williams, F. A. Lattanzio, Jr.; The Terminal Regions of Lacritin May Contain Functional Domains That Increase Tear Flow. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6279.
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© ARVO (1962-2015); The Authors (2016-present)
Lacritin is a stable, novel, naturally occurring human tear glycoprotein that promotes tear secretion in vitro and in vivo and is also reported to be mitogenic. It is speculated that mitogenesis and tear secretion function through independent mechanisms. In this study, the functional domain(s) within bacterial recombinant lacritin that promotes tear secretion was evaluated using deletion mutants of lacritin N-24, N-65 (N-terminal deletions) or C-25 (C-terminal deletions).
Lacritin (50 µg/ml), C-25 (10 µg/ml), N-24 (50 µg/ml), N-65 (50 µg/ml) or artificial tears (control) were administered bilaterally to New Zealand white rabbits three times daily for 14 d (n=6 eyes/group). The treatment period was followed by a 7 d washout period when the rabbits were not treated. Bilateral tear production was measured with Schirmer strips (3 min) at baseline, after 4, 7, 14 d treatment and after washout. For unstimulated tear production, proparacaine (0.5%) was applied 10 min prior to tear flow measurement. Biomicroscopy by slit-lamp was performed weekly. Data are expressed as a percentage of baseline (mean ± SEM).
Treatment with lacritin significantly increased tear flow by 21±5%, 28±7%, or 33±8% after 4, 7, or 14 days of treatment and by 36±5% after washout (p<0.0001, n=6). After N-24 treatment, tear flow was increased by 8±3% from baseline and maintained for the duration of the treatment (p=0.06, n=6). After treatment cessation the tear flow declined to below baseline. Similarly, treatment with N-65 increased tear flow by 6±5% and was maintained until treatment cessation and declined to baseline (p=0.1, n=6). C-25 and artificial tears treatment did not increase tear flow. All treatments were well tolerated as there were no significant signs of ocular irritation detected by slit-lamp examination.
In this study lacritin stimulated tear flow was maintained for up to one week after cessation of therapy. Treatment with deletion mutants N-24 or N-65 increased tear flow minimally, while C-25 treatment did not increase tear flow. This data suggests that functional domains that promote tear secretion might reside within the C (in keeping with co-receptor SDC1 binding) and N terminal regions. Further testing with lacritin deletion mutants that include domains from these terminal regions is warranted.
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