July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Utility of approved dry-eye drugs as reference compounds in SiccaSystemTM - a standardized mouse desiccating stress model for dry-eye disease
Author Affiliations & Notes
  • Simon Kaja
    Experimentica Ltd., Kuopio, Finland
    Ophthalmology, Loyola University Chicago, Maywood, Illinois, United States
  • Symantas Ragauskas
    Experimentica Ltd., Kuopio, Finland
  • Agne Ziniauskaite
    Experimentica Ltd., Kuopio, Finland
  • Anna Mari Haapaniemi
    Experimentica Ltd., Kuopio, Finland
  • Jenni J. Hakkarainen
    Experimentica Ltd., Kuopio, Finland
  • Henna Martiskainen
    Experimentica Ltd., Kuopio, Finland
  • Giedrius Kalesnykas
    Experimentica Ltd., Kuopio, Finland
  • Footnotes
    Commercial Relationships   Simon Kaja, Experimentica Ltd (R), Experimentica Ltd (I), Experimentica Ltd (F), Experimentica Ltd (C), Experimentica Ltd (S), Experimentica Ltd (P), K&P Scientific LLC (I), K&P Scientific LLC (P); Symantas Ragauskas, Experimentica Ltd. (E), Experimentica Ltd. (I); Agne Ziniauskaite, Experimentica Ltd. (E); Anna Haapaniemi, Experimentica Ltd. (E); Jenni Hakkarainen, Experimentica Ltd. (E), Experimentica Ltd. (I); Henna Martiskainen, Experimentica Ltd. (E); Giedrius Kalesnykas, Experimentica Ltd. (E), Experimentica Ltd. (I), Experimentica Ltd. (P), Spouse - Experimentica Ltd. (I), Spouse - Experimentica Ltd. (C)
  • Footnotes
    Support  Experimentica Ltd., Dr. John P. and Therese E. Mulcahy Endowed Professorship in Ophthalmology (SK)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2673. doi:
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      Simon Kaja, Symantas Ragauskas, Agne Ziniauskaite, Anna Mari Haapaniemi, Jenni J. Hakkarainen, Henna Martiskainen, Giedrius Kalesnykas; Utility of approved dry-eye drugs as reference compounds in SiccaSystemTM - a standardized mouse desiccating stress model for dry-eye disease. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2673.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To identify the potential of three approved dry-eye disease (DED) drugs to serve as reference compounds in the standardized SiccaSystemTM mouse experimental platform for experimental dry-eye disease.

Methods : DED was induced in 10-week old male C57Bl/6J mice through exposure to a controlled desiccating environment (<15% humidity, 15 l/min airflow; SiccaSystemTM, K&P Scientific LLC) combined with transdermal scopolamine administration (ScopoDerm®, Novartis). Drugs were applied twice daily into both eyes (10 µl each). Three approved drugs were tested: 0.05% cyclosporine ophthalmic emulsion (Restasis®; Allergan Inc.), 1 mg/ml ophthalmic eye drop emulsion (Ikervis®; Santen Pharmaceutical Co. Ltd.) and 5% ophthalmic lifitegrast solution (Xiidra®; Shire plc). Fluorescein staining was used to quantify corneal surface damage; lacrimal gland pathology and the number of conjunctival goblet cells were quantified using histological analysis.

Results : In a preventative treatment paradigm, Restasis® significantly reduced corneal fluorescein staining (n = 12; P < 0.01) and significantly decreased lacrimal gland pathology (n = 12; P < 0.01). Goblet cell number was 19.1% higher in Restasis®-treated eyes compared with vehicle, but this difference did not reach statistical significance (n = 12; P = 0.52). In a therapeutic treatment paradigm, Restasis® was able to partially reverse disease pathology, as determined by improved corneal fluorescein staining when compared with untreated eyes (n = 9; P < 0.05) or with vehicle (n = 9; P = 0.86). Ikervis® showed similar protection of the cornea as Restasis® when administered in the preventative therapeutic paradigm (n = 8; P = 0.99). In contrast, Xiidra® did not protect against DED-associated pathology. Specifically, Xiidra® did not improve fluorescein staining when administered preventatively (n = 8; P = 0.88) or therapeutically (n = 14; P = 0.45). Similarly, we did not observe any statistically significant effects on lacrimal gland pathology (n = 8; P = 0.62) or the number of conjunctival goblet cells (n = 8; P = 0.99).

Conclusions : Cyclosporine-based formulations can be successfully used to decrease inflammatory pathology in the SiccaSystemTM desiccating environment and scopolamine administration murine DED model. In contrast, the effects of lifitegrast on dry eye-related pathology may be strain- and/or species-dependent.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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