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: Puran S Bora, Jeong-Hyeon Sohn, Jose M C Cruz, Purushottam Jha, Hiroki Nishihori, Yali Wang, Sankaranarayanan Kaliappan, Henry J Kaplan, Nalini S Bora
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 174 Issue 1 Pg. 491-7 (Jan 01 2005) ISSN: 0022-1767 [Print] United States
• PMID: 15611275 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Complement C3
• Complement Membrane Attack Complex
• Transforming Growth Factor beta
• Transforming Growth Factor beta2
• Vascular Endothelial Growth Factor A
• Fibroblast Growth Factors

Topics

• Animals
• Choroid (blood supply)
• Choroidal Neovascularization (etiology, metabolism, physiopathology)
• Complement Activation (physiology)
• Complement C3 (metabolism)
• Complement Membrane Attack Complex (metabolism)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Fibroblast Growth Factors (metabolism)
• Immunohistochemistry
• Lasers (adverse effects)
• Male
• Mice
• Microscopy, Confocal
• Reverse Transcriptase Polymerase Chain Reaction
• Transforming Growth Factor beta (metabolism)
• Transforming Growth Factor beta2
• Vascular Endothelial Growth Factor A (metabolism)