Topical Porphyrin Antioxidant Protects Against Ocular Surface Pathology in a Novel Rabbit Model for Particulate Matter-Induced Dry Eye Disease
Publication: Journal of Ocular Pharmacology and Therapeutics
Volume 38, Issue Number 4
Abstract
Purpose: Particulate matter (PM) is a primary cause for the development of acute and chronic dry eye disease, especially irritant-induced conjunctivitis. The purpose of the present study was to determine the effects of fine atmospheric PM on the rabbit ocular surface, and determine the protective effects of a synthetic antioxidant, manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin (Mn-TM-2-PyP), in vitro and in vivo.
Methods: Rabbit corneal epithelial cells (SIRC) were exposed to increasing concentrations of PM to determine the effects on cell motility and viability. The in vivo effects of topically instilled PM were tested in New Zealand White rabbits. Comprehensive ophthalmic exams and corneal fluorescein staining were performed.
Results: Exposure to PM resulted in dose-dependent cell death and impaired cellular motility; Mn-TM-2-PyP protected against PM-induced cytotoxicity and significantly increased SIRC cell motility. In vivo, exposure to PM (5 mg/ml, topical, 3 times daily for 7 days) resulted in signs of dry eye, notably hyperemia, increased corneal fluorescein staining, and decreased tear volumes. Mn-TM-2-PyP significantly improved hyperemia and corneal fluorescein readouts but had no effect on tear production. Lifitegrast (Xiidra®) showed similar pharmacologic efficacy to Mn-TM-2-PyP.
Conclusion: Overall, these data provide evidence that PM induces phenotypes of ocular surface disease responsive to antioxidant and immunosuppressant therapy. To our knowledge this is the first report of a large animal model to study PM-induced ocular surface disease. The present work provides standardized experimental paradigms for the comprehensive in vitro and in vivo testing of novel therapeutic approaches targeting PM-induced conjunctivitis and dry-eye.
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Information & Authors
Information
Published In
Journal of Ocular Pharmacology and Therapeutics
Volume 38 • Issue Number 4 • May 2022
Pages: 294 - 304
PubMed: 35384749
Copyright
Copyright 2022, Mary Ann Liebert, Inc., publishers.
History
Published online: 3 May 2022
Published in print: May 2022
Published ahead of print: 4 April 2022
Accepted: 4 February 2022
Received: 27 December 2021
Topics
Authors
Authors' Contributions
Conceptualization: A.K.G., M.B.G., and S.K.; methodology: A.K.G., M.B.G., and S.K.; formal analysis: A.K.G., S.I., M.B.G., and S.K.; investigation: A.K.G., M.B.G., S.I., N.E.P., and S.K.; data curation: A.K.G., M.B.G., and S.K.; writing—original draft preparation: A.K.G., M.B.G., S.I., and S.K.; writing—review and editing: A.K.G., M.B.G., S.I., N.E.P., and S.K.; supervision: M.B.G. and S.K.; project administration: M.B.G. and S.K.; funding acquisition: S.K. All authors have read and agreed to the published version of the article.
Author Disclosure Statement
Employment: A.K.G., M.B.G., and N.E.P. (Experimentica Ltd.); Stock/equity ownership: S.K. (Experimentica Ltd.); S.K. (K&P Scientific LLC); A.K.G. (eyeNOS, Inc.). S.K. conducts academic research in areas of interest similar to the business interests of Experimentica Ltd. and K&P Scientific LLC. The terms of this arrangement have been reviewed and approved by Loyola University Chicago in accordance with its conflict-of-interest policy. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the article, or in the decision to publish the results.
Funding Information
This research was funded, in part, by NIH/R24 grant (EY032440). Additional funding by the Illinois Society for the Prevention of Blindness, the Richard A. Perritt, M.D. Charitable Foundation, and the Dr. John P. and Therese E. Mulcahy Endowed Professorship in Ophthalmology is gratefully acknowledged. Experimentica Ltd. and K&P Scientific LLC have provided in kind resources to conduct this study.
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