Structure-Function Correlation in ABCA4-Related Retinopathy

abca4相关视网膜病变是15至65岁人群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。鉴于即将进行的治疗试验，需要经过验证的生物标志物。使用新的成像技术，提交的项目针对视网膜改变的功能相关性，以定义有效的生物标志物。包括两个子项目。第一个子项目涉及定量自体荧光（qAF）的创新诊断工具，该工具最近除其他外由申请人自己的研究建立。qAF使研究者能够客观地成像体内abca4相关视网膜病变的早期视网膜改变。使用眼底控制视野和电生理学，将调查偏离规范数据库的功能相关性。在第二个子项目中，申请人将使用光谱域光学相干断层扫描（OCT）。OCT显示的单层局部改变对功能的影响将通过眼底控制视野和视网膜电图进行研究。形态学改变的功能相关性使研究者能够定义生物标志物和潜在的治疗窗口。所提交项目所需的所有技术设备均已具备。已经有足够多的可能受试者进行了基因分型和表型分型，并表示有兴趣参与该项目。全面的初步工作证实了现有的专门知识。申请德国研究基金会的资助（50%临床义务豁免12个月）是实现所提交项目的基本要求。这个项目意义重大，必须立即启动。

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.