title: Role of complement and complement membrane attack complex in laser-induced choroidal neovascularization.
abstract: Choroidal neovascularization (CNV), or choroidal angiogenesis, is the hallmark of age-related macular degeneration and a leading cause of visual loss after age 55. The pathogenesis of new choroidal vessel formation is poorly understood. Although inflammation has been implicated in the development of CNV, the role of complement in CNV has not been explored experimentally. A reliable way to produce CNV in animals is to rupture Bruch's membrane with laser photocoagulation. A murine model of laser-induced CNV in C57BL/6 mice revealed the deposition of C3 and membrane attack complex (MAC) in the neovascular complex. CNV was inhibited by complement depletion using cobra venom factor and did not develop in C3(-/-) mice. Anti-murine C6 Abs in C57BL/6 mice inhibited MAC formation and also resulted in the inhibition of CNV. Vascular endothelial growth factor, TGF-beta2, and beta-fibroblast growth factor were elevated in C57BL/6 mice after laser-induced CNV; complement depletion resulted in a marked reduction in the level of these angiogenic factors. Thus, activation of complement, specifically the formation of MAC, is essential for the development of laser- induced choroidal angiogenesis in mice. It is possible that a similar mechanism may be involved in the pathophysiology of other angiogenesis essential diseases.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, 301E Muhammad Ali Boulevard, Louisville, KY 40202, USA. psbora01@louisville.edu
authors.forename: Puran S
authors.initials: PS
authors.lastname: Bora
authors.forename: Jeong-Hyeon
authors.initials: JH
authors.lastname: Sohn
authors.forename: Jose M C
authors.initials: JM
authors.lastname: Cruz
authors.forename: Purushottam
authors.initials: P
authors.lastname: Jha
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nishihori
authors.forename: Yali
authors.initials: Y
authors.lastname: Wang
authors.forename: Sankaranarayanan
authors.initials: S
authors.lastname: Kaliappan
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.forename: Nalini S
authors.initials: NS
authors.lastname: Bora
mesh_terms: D000818:Animals; D002829:Choroid / Q000098:blood supply*; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D003167:Complement Activation / Q000502:physiology; D003176:Complement C3 / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005346:Fibroblast Growth Factors / Q000378:metabolism; D007150:Immunohistochemistry; D007834:Lasers / Q000009:adverse effects; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053781:Transforming Growth Factor beta2; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D003176:Complement C3; D015938:Complement Membrane Attack Complex; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors