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Hannah Murray, Beiying Qiu, Will English, Gwendolen Reilly, Xiaomeng Wang; Defining a Novel Role for Complement Factor B in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5476.
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© ARVO (1962-2015); The Authors (2016-present)
Emerging evidence implicates immune imbalance resulting from complement protein deficiency or dysregulation in numerous diseases in which angiogenesis plays a role. Abnormal vascular remodelling and angiogenesis are associated with retinal pathologies such as age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR). Elucidating the role of the complement system in retinal angiogenesis would provide a better insight into the cellular and molecular mechanisms underlying PDR, facilitating the development of alternative or complementary treatments to anti-VEGF therapeutics. This prompted us to investigate the role of the complement system in the context of diabetic retinopathy. By utilising in vitro angiogenesis assays we tested the hypothesis that alternative complement pathway (ACP) component, Complement Factor B (CFB), promotes retinal angiogenesis.
RT-qPCR was used to analyse CFB gene expression in a mouse model of OIR. To evaluate the effect of CFB on retinal angiogenesis, in vitro angiogenesis assays including Matrigel tube formation, cell viability and transwell migration were carried out using human retinal microvascular endothelial cells treated with siRNA targeting CFB (siCFB) and recombinant protein (rhCFB).
In a mouse model of OIR CFB gene expression was increased by 40.25% ± 7.329 (p=0.0117) in comparison to control (normal n=4, OIR n=3). In the Matrigel assay siCFB inhibited tube formation with a reduction of 63.48% ± 7.032 (p=0.0121), 40.36% ± 5.006 (p=0.0150), and 52.84% ± 7.667 (p=0.0205) in number of junctions, total length and total branching length respectively (n=3). siCFB also inhibited HREC migration and viability. rhCFB was able to promote HREC tube formation and viability.
Results are consistent with our hypothesis and suggest CFB has a pro-angiogenic role in retinal angiogenesis.
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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