The role of Angiopoietin 2, PDGF and VEGF in age related macular degeneration and in related animal models.

01/01/2016 to 31/12/2018

Neovascularisation is an important reaction of the body to restore oxygen and nutritional supply to tissues when the original vasculature is damaged, e.g. after trauma. With age related macular degeneration (AMD), choroidal neovascularisation (CNV) is a response to choriocapillaris (CC) breakdown and associated hypoxia during ageing. Several factors have been identified that promote blood vessel outgrowth and CNV, the key angiogenic factors relevant for AMD being vascular endothelial growth factor (VEGF, endothelial cell growth), platelet derived growth factor (PDGF, pericyte coverage of new built vessels) and angiopoietin 2 (Ang2, vessel destabilization and regression). Overexpressing these factors in laboratory animals, here rats, is thought to be a promising approach to study CNV development and the efficacy of anti-angiogenic treatment options.

This work will focus on the following aspects of CNV:
1. Gain deeper understanding of the mediators of choroidal collapse and CNV development by immunohistological and ultrastructural investigation of aged human donor eyes with and without AMD (WP1)
2. Comparative study to evaluate a proper model for CNV (WP2): Evaluation and characterisation of CNV development with special focus on pericyte action in the following angiogenesis models: VEGF, PDGF or angiopoietin2 overexpression in laboratory rats (single subretinal injection of vectors or simultaneous application of two vectors, e.g. VEGF+PDGF overexpression)
3. Efficacy of established and novel anti-angiogenic treatment options in the best of the above mentioned CNV model systems (WP3)

Herewith, this work will investigate the key factors of choroidal collapse in AMD and associated development of CNV. After generation of the animal models for CNV by overexpression of key angiogenic factors, the optimal model will be chosen to investigate the effect of established and novel anti-angiogenic drugs. The gathered results on choroidal neovascularization formation, leakage and the role of pericytes in this context can be used to develop new treatment strategies targeting to either proper stabilization of CNV as a wound healing reaction leading to formation of a “substitute” vascularisation without leakage or proper removal of unwanted vessel growth without affecting the “healthy” surrounding and systemic vasculature.