title: Angiogenesis in eye disease: immunity gained or immunity lost?
abstract: The anti-inflammatory nature of the intraocular environment is critical to the immune privilege of the eye. An important part of immune privilege is the induction of apoptosis by two death-inducing ligands (FasL and TRAIL) that can limit the spread of inflammation and control tumor growth. While initial studies focused on control of inflammation and the impact of these molecules on the systemic immune response, more recent studies have extended this concept to pathogenic neovascularization. This process is an important component of several blinding eye disorders including age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, and corneal disease. These studies showed that the mediators of immune privilege also regulate the extent of angiogenesis. In this article, we will develop the idea that constitutive expression of FasL in the eye, as well as inducible FasL on cells of the immune system, modulates neovascularization in ocular disease. Further, we will present the idea that macrophage participation in this process and their function during disease depends on the microenvironment and the cytokine milieu. These concepts challenge the idea that neovascular eye disease is simply an inflammatory process and support the idea that these diseases may result from the loss or dysfunction of important components of the cellular immune system.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S. Euclid, P.O. Box 8096, St. Louis, MO 63110, USA. ferguson@vision.wustl.edu
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Ferguson
authors.forename: Rajendra S
authors.initials: RS
authors.lastname: Apte
mesh_terms: D000818:Animals; D005128:Eye Diseases / Q000276:immunology* / Q000473:pathology*; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000276:immunology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D053221:TNF-Related Apoptosis-Inducing Ligand