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FASEB J. 2014 Jul;28(7):3171-82. doi: 10.1096/fj.14-251041. Epub 2014 Mar 25.

The alternative complement pathway regulates pathological angiogenesis in the retina.

Author information

1
Angiogenesis Laboratory, Department of Ophthalmology, and.
2
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, and.
3
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.
4
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
5
Angiogenesis Laboratory, Department of Ophthalmology, and kip_connor@meei.harvard.edu.

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.

KEYWORDS:

Cd55; factor b; innate immune system; neovascularization; oxygen-induced retinopathy

PMID:
24668752
PMCID:
PMC4062823
DOI:
10.1096/fj.14-251041
[Indexed for MEDLINE]
Free PMC Article

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