Efficacy of Trabodenoson in a Mouse Keratoconjunctivitis Sicca (KCS) Model for Dry-Eye Syndrome Journal Article

Authors: Žiniauskaite, A.; Ragauskas, S.; Hakkarainen, J. J.; Rich, C. C.; Baumgartner, R.; Kalesnykas, G.; Albers, D. S.; Kaja, S.
Article Title: Efficacy of Trabodenoson in a Mouse Keratoconjunctivitis Sicca (KCS) Model for Dry-Eye Syndrome
Abstract: 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.
Journal Title: Investigative ophthalmology & visual science
Volume: 59
Issue: 7
ISSN: 1552-5783
Publisher: Unknown  
Journal Place: United States
Date Published: 2018
Start Page: 3088
End Page: 3093
Language: eng
Notes: LR: 20190304; JID: 7703701; 0 (Nitrates); 0 (Purinergic P1 Receptor Agonists); 0 (Purines); 0 (trabodenoson); 2018/07/20 06:00 [entrez]; 2018/07/20 06:00 [pubmed]; 2019/03/05 06:00 [medline]; ppublish