Pathophysiologie und Topographie von Schadensmechanismen in AMD-relevanten Tiermodellen (Pathophysiology and topographical distribution of disease mechanisms in animal models relevant for AMD)

• Applicant: Professor Dr. Mathias Seeliger
• Subject Area: Ophthalmology
• Term: from 2000 to 2006
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5244034

Research in most retinal degenerations has been boosted by the availability of transgenic animals that permit the detailed, time-efficient analysis of functional, biochemical, and histological changes associated with the course of these diseases. However, there is no satisfactory model for AMD yet. The purpose of this project is thus to find a pathophysiological model for AMD or at least some of its aspects. To achieve that goal, we will study a new transgenic mouse - the TIMP3 knockin - which is a model for Sorsby's Fundus dystrophy (SFD). As SFD features changes to Bruch's membrane and a choroidal neovascularization, TIMP-3 mice are promising candidates for an AMD model. The mice will be studied in vivo with electrophysiological and fundus imaging methods, accompanied by histological and immunohistochemical work. Following reports of a strong beneficial effect of Vitamin A in SFD patients, we will further attempt to intensify/ameliorate the phenotype in the transgenic mice by means of Vitamin A restriction/supplementation. After the availability of a TIMP3 knockout, this model will also be included in this project. In the later grant periods, animal models that will be generated following the detection of RPE-specific genes by Professor Weber's group will be tested, and therapeutical studies in identified AMD models conducted. Additionally an interesting rat model on ARMD was offered for electrophysiological investigations by Professor Thanos from Münster. Our project has a central role within the Schwerpunkt as it combines the efforts regarding detailed ophthalmological and functional tests in animal models which are also offered to other which are also offered to other participating groups.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1088: Age-Related Macular Degeneration
• Participating Person: Professor Dr. Eberhart Zrenner