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Shawn M Hanks, Joanna Vrouvlianis, Barrett Leehy, Maura Crowley, Michael Maker, Sha-Mei Liao, Bruce D Jaffee, Chad E Bigelow; Impaired alternative complement pathway function does not protect against light-induced retinopathy in mice. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3553.
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Alternative complement pathway-linked genetic polymorphisms are associated with an increased risk of age-related macular degeneration. The purpose of this study is to determine if mice deficient in alternative complement pathway component factor B are protected against light-induced retinal degeneration.
Study was performed on 9-10 week old female complement factor B knockout (FB-/-) mice on a Balb/c background (Leu450 RPE65 isoform) with FB+/+ wild type mice acting as controls. Plasma and ocular FB protein levels were evaluated by western blot. Mice were either dark adapted overnight prior to 12 hours of blue light exposure (~550 lux, 420 nm center wavelength) or were maintained in standard cyclic housing room lighting (<100 lux, white light, 12 hour cycle). Retinal degeneration was assessed using electroretinography (ERG) 1 day after light exposure and by optical coherence tomography (OCT) 2 days after light exposure. Dark-adapted visual function was evaluated by quantifying ERG a-wave amplitude in response to a 2.7 log scot·cd·s·m-2 flash. Retinal thickness was quantified from linear OCT scans centered on the optic nerve. Reported statistical comparisons are only between groups that received blue light (one-way analysis of variance with a Tukey’s posttest).
Western blot analysis confirmed FB-/- mice to be deficient in FB protein for both ocular tissue and plasma. Blue light exposure resulted in similar photoreceptor dysfunction in FB+/+ and FB-/- mice (41% and 57% reduction in ERG a-wave, respectively, P > 0.05). OCT findings were consistent with this result, with blue light exposed FB+/+ and FB-/- mice exhibiting photoreceptor layer thinning (29% and 42%, respectively, P < 0.05).
Mice deficient in alternative complement pathway component factor B exhibit blue light-induced retinal degeneration that is similar to that observed in mice with an intact complement pathway. Loss of factor B does not confer protection against light-induced retinopathy in albino mice.
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