Structure-Function Correlation in ABCA4-Related Retinopathy

与ABCA4相关的视网膜病变是15至65岁年龄段法定失明的最常见原因之一。到目前为止，批准的治疗方法仍在等待中。从即将到来的治疗试验来看，需要经过验证的生物标记物。使用新的成像技术，提交的项目以视网膜变化的功能相关性为目标，以定义有效的生物标记物。其中包括两个子项目。第一个分项目涉及定量自动荧光(QAF)的创新诊断工具，该工具除其他外是由申请人自己的研究建立的。QAF使研究人员能够在活体内客观地成像ABCA4相关视网膜病变的早期视网膜改变。使用眼底控制视野检查和电生理学，将调查与标准数据库的偏差的功能相关性。在第二个子项目中，申请人将使用光谱域光学相干层析成像(OCT)。OCT显示的单层局部改变的功能影响将使用眼底控制视野检查和视网膜电图进行研究。形态变化的功能相关性使研究者能够定义生物标记物和潜在的治疗窗口。提交的项目所需的所有技术设备均可使用。已经对足够多的可能的受试者进行了基因分型和表型分析，并表示有兴趣参与该项目。全面的前期工作证实了现有的专门知识。德国研究基金会申请的资金(12个月内免除50%的临床职责)是实现提交的项目的基本要求。该项目的高度重要性要求立即启动。

ABCA4-related retinopathy is among the most common causes of legal blindness in the age between 15 and 65 years. Up to now, an approved therapy is still pending. In the view of upcoming therapeutic trials, validated biomarkers are required. Using novel imaging techniques, the submitted project targets the functional relevance of retinal alterations in order to define valid biomarkers. Two subprojects are included. The first subproject deals with the innovative diagnostic tool of quantitative autofluorescence (qAF) that was most recently established inter alia by the applicant’s own studies. qAF enables the investigator to objectively image earliest retinal alterations of ABCA4-related retinopathy in-vivo. Using fundus-controlled perimetry and electrophysiology, the functional relevance of deviations from the normative database will be investigated. In the second subproject, the applicant will use the spectral domain optical coherence tomography (OCT). The functional impact of local alterations in single layers visualized by OCT will be investigated using fundus-controlled perimetry and electroretinogram. The functional relevance of morphologic changes enables the investigator to define biomarkers and potential therapeutic windows. All technical devices required for the submitted project are available. More than adequate possible subjects already have been genotyped as well as phenotyped and expressed interest in participation in the project. Comprehensive preliminary work substantiates the available expertise. The requested funding of the German Research Foundation (50% exemption from clinical duties for 12 months) is an essential requirement in order to realize the submitted project. The high significance of the project necessitates an immediate launch.