Efficacy of Trabodenoson in a Mouse Keratoconjunctivitis Sicca (KCS) Model for Dry-Eye Syndrome
| Autor: | Jenni J. Hakkarainen, Giedrius Kalesnykas, David S Albers, Rudolf A. Baumgartner, Cadmus C Rich, Simon Kaja, Symantas Ragauskas, Agne Žiniauskaite |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Conjunctiva genetic structures Dry Eye Syndromes Keratoconjunctivitis Sicca Inflammation Administration Ophthalmic Lacrimal gland 03 medical and health sciences Adenosine A1 receptor Mice 0302 clinical medicine Immune system Cornea medicine Purinergic P1 Receptor Agonists Animals Nitrates business.industry Lacrimal Apparatus Adenosine eye diseases Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Treatment Outcome Purines Tears 030221 ophthalmology & optometry sense organs Goblet Cells medicine.symptom business medicine.drug |
| Zdroj: | Investigative ophthalmologyvisual science. 59(7) |
| ISSN: | 1552-5783 |
| Popis: | 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: | OpenAIRE |
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