Role of macular pigment density in the pathophysiology, clinical outcome and therapy of age-related maculopathy

在工业化国家，年龄相关性黄斑变性（AMD）是50岁以上法律的失明的主要原因。最近的研究表明，黄斑色素（MP）密度可能在疾病的发展和进展中起着中心作用。已经证明，通过膳食补充剂可以增加MP密度。我们的长期目标是确定黄斑色素在AMD发病机制和治疗中的作用。这不仅是为了提高对黄斑色素密度对年龄相关性黄斑病变（ARM）和AMD的影响的理解，也是为了找到一种在治疗干预方面提高黄斑色素密度的方法。用改进的共焦激光扫描检眼镜（Heidelberg Engineering，Heidelberg，德国）测量MP密度的第一结果表明，该方法允许在临床环境中定量MP密度。我们将通过测试其重现性、正确性以及外部/内部因素对测量的影响来评价该方法。10例健康受试者将在4个不同日期接受检查，每个检查日期在1小时内接受两次检查。我们还将优化分析模式，并将结果与替代客观生化方法（HPLC）获得的结果进行比较。对于HPLC分析，我们将在研究中包括来自五只人类供体眼睛的视网膜。随后，我们将建立正常人群的参考值，并将其与横断面研究中从ARM患者中获得的MP密度值进行比较。招募用于定义参考的受试者应为无视网膜病变的受试者;将对30岁至80岁之间每10年20例受试者进行检查。此外，我们将在一项横断面研究中检查ARM和早期萎缩性AMD患者，以获得ARM和AMD患者MP密度值的良好分布。我们将包括单侧和双侧早期疾病或单侧终末期AMD患者的第二只眼。与参考值相比，可以得出关于一方面ARM和AMD以及另一方面MP密度的关系的结论。这将改善从ARM患者获得的MP值的解释，有助于识别MP密度低的患者，并可能改善AMD高危患者的早期诊断。这些任务将在项目的头两年内完成。在这一时期的最后一个季度，我们将详细制定一项前瞻性随机多中心研究方案，研究计划在未来两年进行叶黄素和/或玉米黄质膳食补充剂下的黄斑色素密度。同时，我们将使这种方法可用于DFG优先计划AMD内的所有其他临床研究。具体来说，我们将与H博士教授合作。Hense（明斯特大学），他有兴趣在前瞻性研究中使用这种方法来确定ARM进展的预后因素。总之，这些研究将提高对AMD中MP的理解，并为病理机制的治疗干预开辟前景。

In the industrialised world age-related macular degeneration (AMD) is the leading cause for legal blindness beyond the age of 50 years. Recent studies indicate that the macular pigment (MP) density may play a central role in the development and progression of the disease. It has been demonstrated that the MP density can be increased by dietary supplementation. Our long-term goal is to identify the role of macular pigment in the pathogenesis and therapy of AMD. This is not only to improve understanding about the impact of macular pigment density on age-related maculopathy (ARM) and AMD but also to find an approach to enhance macular pigment density in terms of therapeutic intervention. First results of MP density measurements with a modified confocal laser scanning ophthalmoscope (Heidelberg Engineering, Heidelberg, Germany) show that this method allows the quantification of the MP density in a clinical setting. We will evaluate the method by testing its reproducibility, correctness, and the influence of external/internal factors on the measurements. 10 healthy subjects will be examined at 4 different dates and twice within one hour at each examination date. We will also optimise the mode of analysis and compare the results to those obtained with an alternative objective biochemical method (HPLC). For HPLC analysis we will include retinas from five human donor eyes in the study. Subsequently we will establish reference values for a normal population and compare these to the MP density values obtained from ARM-patients in a cross-sectional study. The persons recruited for defining reference should be subjects without retinal pathology; a number of 20 for each decade between the age of 30 and the age of 80 years will be examined. Additionally we will examine patients with ARM and early atrophic AMD in a cross sectional study in order to achieve a good profile of MP density values in ARM and AMD patients. We will include unilateral and bilateral early disease or the second eye in patients with unilateral end-stage AMD. In comparison to the reference values it could be possible to draw conclusions about the relation of ARM and AMD on one hand and MP density on the other. This will improve the interpretation of MP values obtained from ARM patients, help to identify patients with low MP density, and probably improve the early diagnosis of patients at high risk for developing AMD. These tasks will be performed within the first two years of the project. In the last quarter of this period we will elaborate a study protocol for a prospective randomised multi-center study on the macular pigment density under dietary supplementation of lutein and/or zeaxanthin, which is planned for the following two years. Simultaneously, we will make this method available for all other clinical studies within the DFG-priority program AMD. Specifically, we will collaborate with Prof. Dr. H. Hense (University of Muenster) who is interested in using this method in the prospective study to identify prognostic factors for the progression of ARM. In summary, these studies will improve understanding of MP in AMD and open a perspective for therapeutic interventions in the pathologic mechanisms.