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Feeling Yu Ting Chen, Denise Stephens, Shaokui Ge, Trinka Vijmasi, Gordon W Laurie, Sarah Knox, Nancy A McNamara; Lacritin’s active C-terminal peptide, ‘Lacripep’, as an efficient and innovative therapeutic for the treatment of aqueous-deficient dry eye. . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):300.
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© ARVO (1962-2015); The Authors (2016-present)
Lacritin is a naturally occurring glycoprotein in human tears with prosecretory and mitogenic properties. Previously, we demonstrated the therapeutic benefits of topical lacritin for aqueous-deficient dry eye (ADDE) using the autoimmune-regulator (Aire)-deficient mouse model of Sjögren’s syndrome (SS). Here, we test the therapeutic potential of Lacripep, a synthetic peptide representing lacritin’s active C-terminal 25 amino acids, for the treatment of ADDE.
Six week Aire KO mice were treated 3x daily for 3 weeks with PBS, Lacripep or lacritin, respectively (7, 11 and 8 mice). Tear secretion and corneal lissamine green staining were assessed at 0, 7, 14, and 21 days. At 21 days confocal microscopy was utilized to obtain a preliminary assessment of sensory innervation of the cornea, and immunohistochemistry was used to analyze CD4 T cell infiltration of the cornea and lacrimal gland.
Treatment of Aire KO mice with topical Lacripep or lacritin improved corneal epithelial integrity, as shown by reduced lissamine green staining. Compared to the PBS group, corneal staining scores were more likely to improve in mice treated with Lacripep and lacritin, with odd ratios =17.7 (95% CI: 3.04~178.5) and 23.5 (95% CI: 3.6~265.3), respectively. Tear secretion progressively decreased in eyes treated with PBS, while Lacripep and lacritin maintained tear secretion and restored corneal innervation. Lacripep and lacritin treatment in female Aire KO mice led to tear secretion values 8.84mm (95% CI: 5.47~12.2, p=0.0001) and 5.01mm (95% CI: 2.34~7.67, p=0.0004) higher than Aire KO mice treated with PBS, respectively. Effects in males were less. CD4 T cell infiltration of the cornea and lacrimal gland was unchanged in lacritin-treated mice, whereas Lacripep treatment was resulted in a 48% (95% CI: 36~65%, p < 0.05) decrease in CD4 T cell infiltration of the cornea and a 40.5% (95% CI: 29~52%, p < 0.05) reduction in lymphocytic foci formation in the lacrimal gland.
Lacripep appears to improve corneal epithelial integrity, promote tear secretion, restore sensory innervation and reduce inflammation of the diseased cornea in a mouse model of ADDE. Lacripep’s tear-inducing, neurotrophic and anti-inflammatory properties seem superior to those noted with naturally occurring lacritin, supporting its promise as a novel and potential therapeutic for ADDE.
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