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