Premium
The alternative complement pathway regulates pathological angiogenesis in the retina
Author(s) -
Sweigard J. Harry,
Yanai Ryoji,
Gaissert Philipp,
SaintGeniez Magali,
Kataoka Keiko,
Thanos Aristomenis,
Stahl Gregory L.,
Lambris John D.,
Connor Kip M.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-251041
Subject(s) - complement system , alternative complement pathway , laser capture microdissection , angiogenesis , neovascularization , umbilical vein , retinal , retina , downregulation and upregulation , biology , immunology , microbiology and biotechnology , immune system , chemistry , cancer research , neuroscience , genetics , biochemistry , gene expression , in vitro , gene
A defining feature in proliferative retinopathies is the formation of pathological neovessels. In these diseases, the balance between neovessel formation and regression determines blindness, making the modulation of neovessel growth highly desirable. The role of the immune system in these retinopathies is of increasing interest, but it is not completely understood. We investigated the role of the alternative complement pathway during the formation and resolution of aberrant neovascularization. We used alternative complement pathway–deficient ( Fb –/– ) mice and age‐ and strain‐matched control mice to assess neovessel development and regression in an oxygen‐induced retinopathy (OIR) mouse model. In the control mice, we found increased transcription of Fb after OIR treatment. In the Fb –/– mice, we prepared retinal flatmounts and identified an increased number of neovessels, peaking at postnatal day 17 (P17; P =0.001). Subjecting human umbilical vein endothelial cells (HUVECs) to low oxygen, mimicking a characteristic of neovessels, decreased the expression of the complement inhibitor Cd55 . Finally, using laser capture microdissection (LCM) to isolate the neovessels after OIR, we found decreased expression of Cd55 ( P =0.005). Together, our data implicate the alternative complement pathway in facilitating neovessel clearance by down‐regulating the complement inhibitor Cd55 specifically on neovessels, allowing for their targeted removal while leaving the established vasculature intact.—Sweigard, J. H., Yanai, R., Gaissert, P., Saint‐Geniez, M., Kataoka, K., Thanos, A., Stahl, G. L., Lambris, J. D., Connor, K. M. The alternative complement pathway regulates pathological angiogenesis in the retina. FASEB J . 28, 3171–3182 (2014). www.fasebj.org