Efficacy of Trabodenoson in a Mouse Keratoconjunctivitis Sicca (KCS) Model for Dry-Eye Syndrome.
| Autor: | Žiniauskaite A; Experimentica Ltd., Kuopio, Finland., Ragauskas S; Experimentica Ltd., Kuopio, Finland., Hakkarainen JJ; Experimentica Ltd., Kuopio, Finland., Rich CC; Inotek Pharmaceuticals Corp., Lexington, Massachusetts, United States., Baumgartner R; Inotek Pharmaceuticals Corp., Lexington, Massachusetts, United States., Kalesnykas G; Experimentica Ltd., Kuopio, Finland., Albers DS; Inotek Pharmaceuticals Corp., Lexington, Massachusetts, United States., Kaja S; Experimentica Ltd., Kuopio, Finland.; Departments of Ophthalmology and Molecular Pharmacology and Therapeutics, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2018 Jun 01; Vol. 59 (7), pp. 3088-3093. |
| DOI: | 10.1167/iovs.18-24432 |
| Abstrakt: | Purpose: To determine the efficacy of trabodenoson, an adenosine mimetic with highly selective adenosine A1 receptor binding properties, in a preclinical mouse model for dry-eye disease. Methods: Dry-eye disease was induced in adult male C57BL/6 mice using a combination of desiccating environment and transdermal administration of scopolamine. Mice were treated concurrently and twice daily with either vehicle, 6% trabodenoson, or 0.05% cyclosporine (Restasis). Efficacy (P < 0.05 versus vehicle) was determined by clinical assessment of dry-eye symptoms using corneal fluorescein staining and tear volumes and histopathologically by quantifying lacrimal gland pathology and conjunctival goblet cells. Results: Twice-daily topical (ocular) administration of trabodenoson increased tear levels and reduced corneal fluorescein staining (P < 0.05) as compared with vehicle-treated eyes in a mouse model of dry-eye disease. Furthermore, significant infiltration of immune cells in the lacrimal gland and reduced number of mucin-producing conjunctival goblet cells were noted in both untreated and vehicle-treated eyes. Comparatively, trabodenoson treatment significantly reduced lacrimal gland infiltration and increased the number of goblet cells (P < 0.05 for both versus vehicle). These trabodenoson-related effects on lacrimal gland pathology and goblet cells were similar to or better than the effects observed with cyclosporine treatment. Conclusions: Topical ocular delivery of trabodenoson significantly improves the clinical and histopathological signs associated with dry-eye disease in mice. This improvement appears to be related to anti-inflammatory effects from targeting adenosine signaling and represents a novel therapeutic approach to develop for the management of dry-eye disease. |
| Databáze: | MEDLINE |
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