Influence of inflammatory mediators on RPE barrier function and choroidal neovascularization

• Applicant: Professorin Dr. Antonia Joussen
• Subject Area: Ophthalmology
• Term: from 2004 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5434230

Leukocytes have been implicated in the pathogenesis of AMD because their spatiotemporal distribution correlates with arborizing CNV in humans and in animal models. The proangiogenic growth factor VEGF induces the expression of intercellular adhesion molecule 1 (ICAM 1) on vascular endothelium and regulates leukocyte adhesion to endothelial cells. These systems are intertwined as leukocytes, which possess receptors for and migrate in response to VEGF, can also produce and release VEGF. It is currently believed that pathological angiogenesis is a manifestation of an imbalance between two growth factor families: the VEGF/Flt-1 system and the angiopoietin1, 2/Tie1,2 system. Ang-1 stabilizes vessels, whhereas Ang-2 promotes vascular remodeling in combination with VEGF and vessel regression in the absence of VEGF. The Fas-FasL system has been demonstrated to exert an inhibitory role by reducing endothelial sprouting. The discussion of a primary role of inflammation versus a secondary cause of choroidal neovascularization is stillnot solved, however there is evidence that the RPE cells via expression of pro- and anti-angiogenic molecules might play a central role. we use two transgenic mouse models to investigate whether the expression of those molecules within RPE cells is sufficient to regulate the angiogenic process that leads to choroidal neovascularization or whether ruptures of Bruch's membrane with or without inflammatory stimuli are prerequisite for the initiation of choroidal neovascularization. These experiments might shed light on the pathogenesis of choroidal neovascularization and help in the search for causal therapeutic strategies.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1088: Age-Related Macular Degeneration
• Participating Person: Professor Dr. Sascha Fauser
• Ehemaliger Antragsteller: Professor Dr. Bernd Kirchhof