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

AMD 相关动物模型疾病机制的病理生理学和地形分布

• 批准号: 5244034
• 负责人: Professor Dr. Mathias Seeliger
• 金额: --
• 依托单位: Arbeitsgruppe Neurodegeneration des Auges
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2000
• 资助国家: 德国
• 起止时间: 1999-12-31 至 2005-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5244034?language=en
• 关键词: Pathophysiologie; und; Topographie; von; Schadensmechanismen

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.

转基因动物的出现促进了对大多数视网膜变性的研究，这些转基因动物允许对与这些疾病过程相关的功能、生化和组织学变化进行详细、省时的分析。然而，目前还没有一款令人满意的AMD机型。因此，该项目的目的是找到AMD的病理生理学模型或至少其某些方面。为了实现这一目标，我们将研究一种新的转基因小鼠-TIMP 3敲入-这是一种Sorsby眼底营养不良（SFD）的模型。由于SFD的特征是布鲁赫膜和脉络膜新生血管的变化，TIMP-3小鼠是AMD模型的有希望的候选者。将采用电生理学和眼底成像方法对小鼠进行体内研究，同时进行组织学和免疫组织化学工作。在报道了维生素A对SFD患者的强烈有益作用后，我们将进一步尝试通过维生素A限制/补充来加强/改善转基因小鼠的表型。TIMP 3敲除可用后，该模型也将纳入本项目。在后期的资助期间，将对韦伯教授的小组检测RPE特异性基因后产生的动物模型进行测试，并在确定的AMD模型中进行治疗研究。此外，来自明斯特的Thanos教授还提供了一种有趣的ARMD大鼠模型用于电生理研究。我们的项目在Schwerpunkt中发挥着核心作用，因为它结合了在动物模型中进行详细的眼科和功能测试的努力，这些测试也提供给其他参与团体。