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Thirugnana Vijmasi, Feeling Yu Ting Chen, Robert McKown, Gordon Laurie, Nancy McNamara; Topical administration of lacritin promotes tear secretion and improves ocular surface integrity in a mouse model of autoimmune dry eye. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2667. doi: https://doi.org/.
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Lacritin is a recently discovered glycoprotein component of the tear fluid that has been noted for its pro-secretory properties. We investigated whether the topical administration of recombinant lacritin led to increased tear secretion in the AutoImmune REgulator (AIRE)-deficient mouse model of aqueous deficient dry eye.
We used a paired-eye study design to compare the treatment effect of recombinant lacritin (50µg/mL) versus vehicle control (PBS). AIRE knockout (KO) mice bred on NOD and BALB-c backgrounds (n=7) were treated three times daily for 21 days with 10µL of lacritin or vehicle control. Pilocarpine induced tear secretion was measured using Zone-Quick Phenol-Red tear strips and ocular surface integrity was assessed by lissamine green staining. Tear secretion and lissamine green staining were assessed at baseline and after one and three weeks of treatment. Lissamine green staining was scored on a 4-point scale by four masked and experienced observers. After 21 days of treatment, CD4+ T cell infiltration of the ocular surface was assessed by immunohistochemical staining.
Tear flow was increased in the eyes of Aire-deficient mice treated with lacritin at all time points of evaluation. Within one week, tear secretion increased by 36% in lacritin vs. PBS treated eyes (13.7±2.4 vs. 10.0±2.0 mm of wetting; P=0.003) and was further increased by 59% at the third week (12.3±3.1 vs. 7.75±2.8 mm of wetting; P=0.005). The change in lissamine green staining relative to pre-treatment levels was unaltered in lacritin-treated eyes after one week of therapy versus an appreciable increase in staining for PBS treated eyes (0.0±0.06 vs. 0.78±0.06; P=0.08). By three weeks, lissamine green staining had significantly decreased in lacritin-treated eyes while lissamine green scores in PBS-treated eyes continued to be elevated relative to baseline (-0.417± 0.06 vs. 0.125 ± 0.07; P=0.02). Lacritin treatment, however, did not influence either the number or the pattern of CD4+ T-cell infiltration to the ocular surface.
We have shown that topically administered recombinant lacritin increases tear secretion and improves ocular surface integrity in a mouse model of aqueous tear deficiency. These data provide evidence to support the therapeutic potential of lacritin in the treatment of dry eye
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