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Topical cis-urocanic acid prevents ocular surface irritation in both IgE -independent and -mediated rat model

  • Basic Science
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Abstract

Purpose

Our purpose was to investigate the effect of locally administered cis-urocanic (cis-UCA) in two experimental models of allergic conjunctivitis.

Methods

The compound 48/80 (C48/80)-induced ocular irritation model (IgE-independent) and the ovalbumin (OA)-induced ocular allergy model (IgE-mediated) were used to test and compare the effect of cis-UCA on dexamethasone, ketotifen and olopatadine. In the C48/80 model, clinical severity scoring from photographs, immunohistochemical analysis of nuclear Ki-67 antigen to quantify actively proliferating epithelial cells and of caspase-3 enzyme to identify apoptotic activity in the conjunctival tissue were used. In the OA model, an Evans Blue stain concentration of conjunctival tissue was used to evaluate vascular leakage due to allergic reaction.

Results

The cis-UCA was well tolerated and effective in both the IgE-independent and -mediated rat models. Treatment with C48/80 caused conjunctival hyperaemia, which was significantly inhibited by ketotifen at the 6 h time point (p = 0.014) and by dexamethasone and cis-UCA 0.5% at 12 (p = 0.004) and 24 (p = 0.004) hour time points. In a comparison between the active drug treatments, only ketotifen showed a significant difference (p = 0.023) to cis-UCA treatment at the 1 h time point, otherwise there were no statistically significant differences between the active drugs. Ketotifen, dexamethasone and cis-UCA 0.5% significantly inhibited the C48/80-induced nuclear accumulation of Ki-67, without differences between the active treatment groups. In the OA model, cis-UCA 0.5% did not inhibit the vascular leakage of conjunctiva, whereas cis-UCA 2.5% of was at least equally effective compared to olopatadine, abolishing the allergic vascular leakage response almost completely.

Conclusions

The present findings in the two AC models suggest that cis-UCA might have anti-allergic potency both in immediate and delayed-type allergic reactions in the eye.

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Funding

No funding was received for this research.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland

    Hanna-Mari Jauhonen & Kai Kaarniranta

  2. Institute of Clinical Medicine, Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland

    Hanna-Mari Jauhonen, Johanna Viiri & Kai Kaarniranta

  3. Department of Ophthalmology, University of Eastern Finland and Kuopio University Hospital, Finland, P.O. Box 1627, FIN-70211, Kuopio, Finland

    Hanna-Mari Jauhonen

  4. BioCis Pharma Ltd, Turku, Finland

    Jarmo Laihia & Lasse Leino

  5. Santen Oy, Tampere, Finland

    Olli Oksala & Päivi Alajuuma

  6. Institute of Clinical Medicine, Department of Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland

    Reijo Sironen

  7. Department of Pathology, Kuopio University Hospital, Kuopio, Finland

    Reijo Sironen

Authors
  1. Hanna-Mari Jauhonen
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  2. Jarmo Laihia
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  4. Johanna Viiri
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  8. Lasse Leino
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Correspondence to Hanna-Mari Jauhonen.

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Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.

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Jauhonen, HM., Laihia, J., Oksala, O. et al. Topical cis-urocanic acid prevents ocular surface irritation in both IgE -independent and -mediated rat model. Graefes Arch Clin Exp Ophthalmol 255, 2357–2362 (2017). https://doi.org/10.1007/s00417-017-3781-z

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  • DOI: https://doi.org/10.1007/s00417-017-3781-z

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