Age-related macular degeneration: Regulative mechanisms of cell death and survival; effects of hypoxia

• Applicant: Professorin Dr. Charlotte Remé
• Subject Area: Ophthalmology
• Term: from 2000 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5244520

Worldwide about 8 Million people are legally blind due to age related macular degeneration (AMD) and the number of individuals with severe visual impairment due to AMD is a multiple. The prevalence of AMD is increasing inter alia due to an increase in average life span. During the pathogenesis of AMD the pigment epithelial cells and the visual cells of the retina are lost by apoptosis, a particularly regulated form of cell death. Our work aims at understanding and preventing photoreceptor approtection), as one key strategy to rescue vision in AMD. We recently showed that one of the prime molecules (vascular endothelial growth factor, VEGF) in the induction of neovascularisation - another hallmark of AMD - also might be involved in the induction of photoreceptor apoptosis. This may be a new and important characteristic of VEGF with important implications for future AMD therapies. We will continue testing treatments (pharmacologically or virally mediated) to achieve inhibition of the VEGF system to interfere with cell loss. Furthermore, we will analyze the molecular mechanisms of this interference. The recently revived implications of an involvement of the immune system - in particular macrophages - in AMD will be considered by the following approach: Transgenic mice with functionally impaired macrophages and/or other phagocytes will be tested for their ability to cope with apoptotic photoreceptors in the retina after induced retinal degeneration. In addition, the outcome of macrophage/phagocyte impairment over time will be assessed in aged mice based on the hypothesis that an initial event in AMD is an insufficiency of these systems to properly dispose waste material from the retina. Together, these studies will shed new light on one of the currently most favored strategies (inhibition of VEGF) to counteract neovascularisation in AMD and will for the first time provide molecular insights into the newly discovered role of macrophages in AMD.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1088: Age-Related Macular Degeneration
• International Connection: Switzerland
• Participating Person: Professor Dr. Christian Grimm