Abstract
Purpose :
Dry eye syndrome (Keratoconjunctivitis sicca; KCS) is a multifactorial disease of the tear glands and ocular surface. Currently available treatments are only partially effective and novel strategies for KCS pharmacotherapy are urgently needed. However, advances in the development of anti-KCS drugs are hindered by a lack of standardized and validated desiccating environment chambers.
Methods :
Experimental KCS was induced in 6 week-old C57BL/6 mice by exposure to a novel desiccating environment chamber (SiccaSystemTM, K&P Scientific LLC, Hines, IL) and concurrent transdermal administration of scopolamine for 10 days. Air flow and humidity were set at 15 L/min and 5%, respectively. In order to validate the SiccaSystemTM chamber, one group of mice was treated with Restasis® (0.05% Cyclosporine Ophthalmic Emulsion, Allergan, Irvine, CA), applied topically as eye drops twice daily into the right eye; the left eye served as untreated control. We quantified lacrimal gland pathology and severity of KCS symptoms by grading the extent of mononuclear cell infiltration in the lacrimal gland and quantification of corneal epithelial thickness, goblet cell number and tear volume.
Results :
Exposure to the SiccaSystemTM desiccating environment with concurrent scopolamine administration resulted in significant focal accumulation of mononuclear cells in the lacrimal gland and notable parenchymal damage. Thickness of the conjunctival epithelium increased from 16.3 µm to 19.60 µm (P<0.05), while tear volume was reduced by 50% (P<0.05). Topical administration of Restasis® significantly improved lacrimal gland pathology compared to control eyes.
Conclusions :
We developed and successfully validated the SiccaSystemTM desiccating environment chamber. Restasis®, the only currently FDA-approved drug for KCS, showed efficacy against lacrimal gland damage and other quantitative KCS readouts, serving as a benchmark for future, novel anti-KCS drugs. In conclusion, the SiccaSystemTM chamber will facilitate development of novel KCS pharmacotherapies by providing a novel validated standardized experimental platform for drug discovery for KCS.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.