July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
Experimental immune-mediated conjunctivitis (EIC): downregulation by Coversin, a dual C5 and LTB4 inhibitor
Author Affiliations & Notes
  • Virginia Calder
    UCL Institute of Ophthalmology, University College London, London, United Kingdom
  • Malihe Eskandarpour
    UCL Institute of Ophthalmology, University College London, London, United Kingdom
  • Xiaozhe Zhang
    UCL Institute of Ophthalmology, University College London, London, United Kingdom
  • Yi-Hsing Chen
    UCL Institute of Ophthalmology, University College London, London, United Kingdom
    Department of Ophthalmology, Chang Geng Memorial Hospital, Taoyuan, Taiwan
  • Miles Nunn
    UCL, London, United Kingdom
    Akari Therapeutics Plc, London, United Kingdom
  • Wynne Weston-Davies
    Akari Therapeutics Plc, London, United Kingdom
  • Footnotes
    Commercial Relationships   Virginia Calder, Akari Therapeutics plc (F), Akari Therapeutics plc (R); Malihe Eskandarpour, None; Xiaozhe Zhang, None; Yi-Hsing Chen, None; Miles Nunn, Akari Therapeutics plc (E); Wynne Weston-Davies, Akari Therapeutics plc (E)
  • Footnotes
    Support  Research Collaborative Grant from Akari Therapeutics plc
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 507. doi:https://doi.org/
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      Virginia Calder, Malihe Eskandarpour, Xiaozhe Zhang, Yi-Hsing Chen, Miles Nunn, Wynne Weston-Davies; Experimental immune-mediated conjunctivitis (EIC): downregulation by Coversin, a dual C5 and LTB4 inhibitor
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):507. doi: https://doi.org/.

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

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Abstract

Purpose : Atopic keratoconjunctivitis (AKC) is difficult to treat and can lead to corneal cicatrisation and vision loss. Topical or systemic immunosuppression may be necessary to prevent disease progression. Coversin, a therapeutic peptide, was applied in a model of experimental immune-mediated conjunctivitis (EIC) to test the hypothesis that combined complement C5 and LTB4 inhibition might mitigate conjunctival inflammation.

Methods : EIC was induced in 8-10 week old female C57/Bl6 mice (N=8 per group) following ip immunisation with ovalbumin (OVA)[1] and bilateral daily challenge with topical 250ug OVA. Ocular surface inflammation was detectable from Day 14 onwards. Topical Coversin at various concentrations (0.063%-0.5%) was used twice daily in both eyes from Day 15 for 5 days. Placebo-treated and unchallenged groups were used as controls. Two additional groups were treated with EV131 (1%), a histamine binding protein, alone and in conjunction with Coversin. All eyes were examined daily by two masked observers and summative clinical scores for redness, chemosis and tearing were assessed from Day 17 to Day 21. Animals were euthanised and ocular tissues harvested on Day 21 for histology, flow cytometry and cytokine levels.


[1] Adahome SD et al. JCI Insight. 2016 Aug 4;1(12):e87001

Results : Coversin (0.063 - 0.25%) was significantly effective in downregulating EIC compared to placebo on Day 20 [p=0.008] but no treatment was effective at earlier time points. Other concentrations and EV131 alone or in combination with Coversin were less effective. Histological findings matched the clinical scores. Conjunctival CD4+ T cells were elevated in all treatment groups compared to unchallenged animals but CD4+FOXP3+ Treg cells were minimal throughout. By contrast, Pu.1+GATA3- T cells (Th9) were increased in all OVA challenged groups and were significantly inhibited by Coversin.

Conclusions : Topical Coversin significantly suppressed ocular surface inflammation in EIC although the effect was only significant on day 4 of treatment. This suggests that inhibiting immune cell trafficking by complement C5 and LTB4 scavenging is a potential novel therapeutic approach to the treatment of severe immune-mediated conjunctivitis, such as AKC.

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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