September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
A topically delivered synthetic metalloporphyrin SOD mimetic improves hallmarks of dry-eye disease pathology.
Author Affiliations & Notes
  • Simon Kaja
    Ophthalmology, Loyola University Chicago, Maywood, Illinois, United States
    Research Service, Edward Hines Jr. VA Hospital, Hines, Illinois, United States
  • Peter Koulen
    Ophthalmology, University of Missouri - Kansas City, Kansas City, Missouri, United States
  • Jooseppi Puranen
    Experimentica Ltd., Kuopio, Finland
  • Symantas Ragauskas
    Experimentica Ltd., Kuopio, Finland
    State Research Institute for Innovative Medicine, Vilnius, Lithuania
  • Footnotes
    Commercial Relationships   Simon Kaja, Experimentica Ltd. (F), Experimentica Ltd. (I), Experimentica Ltd. (C), Experimentica Ltd. (R), Experimentica Ltd. (S), Experimentica Ltd. (P), K&P Scientific LLC (I); Peter Koulen, None; Jooseppi Puranen, Experimentica Ltd. (E); Symantas Ragauskas, Experimentica Ltd. (E)
  • Footnotes
    Support  Dr. John P. and Therese E. Mulcahy Endowed Professorship in Ophthalmology; NIH: EY015672, RR027093 (PK); Felix and Carmen Sabates Missouri Endowed Chair in Vision Research (PK); Challenge Grant from Research to Prevent Blindness (PK); Vision Research Foundation of Kansas City (PK)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 396. doi:
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    • Get Citation

      Simon Kaja, Peter Koulen, Jooseppi Puranen, Symantas Ragauskas; A topically delivered synthetic metalloporphyrin SOD mimetic improves hallmarks of dry-eye disease pathology.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):396.

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

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Abstract

Purpose : Dry eye syndrome (Keratoconjunctivitis sicca; KCS) is a multifactorial disease of the tear glands and ocular surface, which may result from increased tear evaporation or insufficient tear production. Among others, common causes for KCS are aging, drug side effects and autoimmune diseases. Increased tissue levels of reactive oxygen species and the ensuing oxidative stress are common hallmarks of both aqueous tear-deficient and autoimmune KCS. Based on the rationale that oxidative stress contributes to the characteristic lacrimal gland pathology in KCS, we hypothesized that topical antioxidant therapy can restore lacrimal gland function and, thereby, improve KCS pathology.

Methods : Six week-old wild-type C57BL/6 mice were exposed to a desiccating environment chamber (SiccaSystemTM, K&P Scientific LLC, Hines, IL) for 10 days. Air flow and humidity were set at 15 L/min and 5%, respectively. Concomitantly, animals received transdermal application of scopolamine. The superoxide dismutase (SOD) mimetic Manganese(III)-5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin Pentachloride (MnTM-2-PyP; EMD Millipore, Billerica, MA), was applied topically diluted in physiological saline at 0.05% (w/v) twice daily into the left eye. The right eye was treated with saline and served as control. We quantified lacrimal gland pathology and severity of KCS symptoms by grading the extent of mononuclear cell infiltration in the lacrimal gland and by measuring corneal epithelial thickness. Tear volume was determined using phenol red-coated threads.

Results : The combined desiccating environment/scopolamine treatment resulted in significant focal accumulation of mononuclear cells in the lacrimal gland with mild parenchymal damage. Topical administration of MnTM-2-PyP significantly improved lacrimal gland pathology compared to saline control. Specifically, we observed improvement of all quantitative readouts for assessing KCS severity including an absence of parenchymal damage and fewer areas of focal accumulation of immune cells, resulting in a reduction of the lacrimal gland pathology score from 2.25 ± 0.3 to 1.2 ± 0.5 (P<0.05).

Conclusions : MnTM-2-PyP, a prototypic synthetic metalloporphyrin compound with potent catalytic antioxidant activity, improves lacrimal gland pathology in a preclinical model for KCS. Topical antioxidant therapy may thus provide a feasible approach for KCS pharmacotherapy.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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