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Ryo Mukai, Yoko Okunuki, Garrett Klokman, Saori Inafuku, Clifford Kim, Dongho Park, Deeba Husain, Kip M Connor; The Complement System is required in maintaining retinal function. Invest. Ophthalmol. Vis. Sci. 2017;58(8):272. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The complement system is a hub-like surveillance network of the innate immune system that plays a vital role in the modulation of immune and inflammatory responses. In addition to the well-established actions of complement in the elimination of pathogens, the complement system has recently been implicated in a variety of pathophysiological processes, including photoreceptor degeneration and vascular regression. However, to date, the role of the complement system in the normal healthy retina is largely unknown. We tested the hypothesis that the complement system (classic, alternative, and mannose binding lectin pathways) might play an important role in retinal homeostasis.
Using young (6 week-old) and adult (6 month-old) mice in both wild type (C57BL/6) and complement knockout strains (C1q-/-, Mbl-/-, Fb-/-, C3-/-, and C5-/-), we compared amplitudes of electroretinograms and thickness of retinal layers with spectral domain optical coherence tomography between young and adult mice. Additionally, we also assessed retinal architecture in these animals by light and electron microscopy.
There were no significant differences in amplitude or thickness of the inner nuclear layer (INL) between young and adult C57BL/6 mice. However, the amplitudes in old mice were significantly decreased compared to that of young mice in all complement knockout strains (a-wave: C1q-/- p<0.001, Mbl-/- p <0.0001, Fb-/- p <0.0001, C3--/ p <0.0001, and C5-/- p <0.0001; b-wave: C1q-/- p<0.0001, Mbl-/- p <0.0001, Fb-/- p <0.0001, C3--/ p <0.0001, and C5-/- p <0.0001), and there were significant decreases in INL thickness in adult compared to young mice in all complement knockout strains (p <0.0001 in all strains). INL thinning was observed in C1q-/- and C3-/- strains at the age of 6 months compared to 6 weeks in light microscopy. In electron microscopy, dense fractions in the outer plexiform layer, which suggests destruction of synapses between photoreceptor cells and bipolar cells, were observed in Mbl-/-, Fb-/-, C3-/-, and C5-/- in both young and old mice. Additionally, at the age of six months basal lamina deposits were observed in Fb-/- strain, and RPE proliferation and attenuation in C5-/- strain.
These data suggest that the complement system is vital to maintaining retinal homeostasis and that deficiency in the complement system can lead to a loss of normal retinal integrity.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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