June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Leukotriene B4 (LTB4) in the progression of retinal inflammation in experimental autoimmune uveitis (EAU)
Author Affiliations & Notes
  • Mali Eskandarpour
    Ocular Biology & Therapeutics, UCL, London, ENGLAND, United Kingdom
  • Wynne Weston-Davies
    Akari Therapeutics, London, United Kingdom
  • Virginia L Calder
    Ocular Biology & Therapeutics, UCL, London, ENGLAND, United Kingdom
  • Miles Nunn
    Akari Therapeutics, London, United Kingdom
  • Footnotes
    Commercial Relationships   Mali Eskandarpour, None; Wynne Weston-Davies, None; Virginia Calder, None; Miles Nunn, None
  • Footnotes
    Support  not abblicable
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3679. doi:
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      Mali Eskandarpour, Wynne Weston-Davies, Virginia L Calder, Miles Nunn; Leukotriene B4 (LTB4) in the progression of retinal inflammation in experimental autoimmune uveitis (EAU). Invest. Ophthalmol. Vis. Sci. 2020;61(7):3679.

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

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Abstract

Purpose : To investigate the involvement of the LTB4 pathway in EAU disease progression.

Methods : To induce EAU, female C57Bl/6 mice, aged 5-8 weeks, were immunized with IRBP1-20 (Cortes LM et al, 2008). At different time points post immunization, vitreous fluids (5-10 µL) were extracted and assayed for LTB4 levels by ELISA (R&D systems). Chemically synthesised LTB4 (C20H32O4; 100 pM) was intravitreally introduced (1-2 µL) into healthy mice and changes to the retina/choroid were monitored by retinal fundoscopy and angiography at different time points post immunization. EAU disease progression was graded clinically when mice were intravitreally treated by the LTB4-specific inhibitor, L-nomacopan, a recombinant protein derived from the saliva of blood-feeding ticks.

Results : A significantly increased level of LTB4 was detected (30-200 pg/mL; P<0.03) in 19 vitreous fluids extracted from two eyes per mouse (n=30) at different stages of disease relative to controls (day 5, 39.4±10.9 pg/mL, n=7, P=0.03; day 12, 98.4±40.88 pg/mL, n=9, P=0.044). We also found that introducing LTB4 intravitreally induced an observed increase in vascular permeability and recruitment of myeloid cells (CD11b, CD11c, Ly.6c) into the vitreoretinal space. Targeting LTB4 by intravitreal L-nomacopan inhibited vascular permeability and suppressed disease progression as monitored. We are currently investigating LTB4 levels and their correlation with clinical features (vessel cuffing, tissue inflammation and damage).

Conclusions : Using in vivo models, LTB4 plays an important role during disease progression and specific inhibitors can mitigate EAU progression in a therapeutic approach.

This is a 2020 ARVO Annual Meeting abstract.

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