title: The alternative complement pathway regulates pathological angiogenesis in the retina.
abstract: 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.
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, and.
authors.forename: J Harry
authors.initials: JH
authors.lastname: Sweigard
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, and.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yanai
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, and.
authors.forename: Philipp
authors.initials: P
authors.lastname: Gaissert
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, and.
authors.forename: Magali
authors.initials: M
authors.lastname: Saint-Geniez
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, and.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, and.
authors.forename: Aristomenis
authors.initials: A
authors.lastname: Thanos
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; and.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Stahl
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, and kip_connor@meei.harvard.edu.
authors.forename: Kip M
authors.initials: KM
authors.lastname: Connor
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018958:CD55 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003170:Complement Pathway, Alternative / Q000502:physiology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism; D012160:Retina; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology; D015861:Retinal Neovascularization / Q000378:metabolism / Q000473:pathology*
chemical_list: D018958:CD55 Antigens; D010100:Oxygen
keywords: Cd55; factor b; innate immune system; neovascularization; oxygen-induced retinopathy