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Paula Kataguiri, Wei-Sheng Chen, Zhiyi Cao, Victor Sendra, Pedram Hamrah, Driss Zoukhri, Kenneth Kenyon, M. Elizabeth Fini, Shinwu Jeong, Noorjahan A Panjwani; Galectin-1 ameliorates dry eye disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):425.
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© ARVO (1962-2015); The Authors (2016-present)
Dry eye disease (DED) is a prevalent multifactorial disease of tears and ocular surface, recently recognized as an inflammatory disease, that alters the corneal epithelial barrier and damages ocular surface. Galectins are a family of animal lectins capable of recognizing β-galactosides and they have emerged as potent immunoregulatory agents. Galectin-1 (Gal-1) is considered an anti-inflammatory galectin. In this study, we assess the role of Gal-1 in a murine model of DED.
The air-draft-plus-scopolamine protocol was used to induce desiccating stress. Scopolamine hydrobromide (1 mg in 0.1 ml of 1.5% hydroxyethyl cellulose/PBS) was subcutaneously injected, twice a day for 5 days with air flow from fans. To determine the role of endogenous Gal-1 in DED, desiccating stress was induced in Gal-1 knockout (KO) mice and wildtype (WT) mice. To determine the therapeutic potential of recombinant Gal-1 on dry eye disease, desiccating stress was induced in WT mice, and recombinant Gal-1 in PBS (10 µg/10µl) or PBS alone were injected subconjunctivally on alternate days beginning on day 0. To assess the corneal epithelial barrier function, corneal fluorescein staining was performed with standardized grading on days 0, 2 and 5 post-desiccating stress. Additionally, tear production was measured with phenol red impregnated cotton threads. At the end of the experiments, corneas were harvested and processed for whole-mount corneal staining with an anti-LYVE-1 antibody. Lymphangiogenic areas of the cornea were calculated using ImageJ. Data were analyzed using the Mann-Whitney U test.
Compared to WT mice, Gal-1 KO mice had worse corneal epithelial barrier function on days 2 and 5 post-DS (N=20 for each group, p<0.001) as determined by corneal fluorescein staining. Conversely, subconjunctival injections of recombinant Gal-1 markedly improved corneal epithelial barrier function on day 5 post-desiccating stress (N=10 for each group, p<0.001). Lymphangiogenic areas were higher in Gal-1 KO mice than in WT mice (p<0.001) on day 5 post- desiccating stress. In contrast, lymphangiogenic areas were lower in recombinant Gal-1-treated mice than in PBS-treated mice (p<0.01) on day 5-post- desiccating stress.
Utilizing a standardized animal model, we have shown that galectin-1 plays an important role in modulating DED and that administration of recombinant galectin-1 might be a potential new strategy in treating DED.
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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