SGER: Image Analysis Mapping of A2E Retinal Molecular Pathway

A2PE*H2是视网膜光感受器外节段高全反式生成（即受体光色素漂白）期间产生的二次不可逆光化学产物。它在505nm处有最大吸收，在620nm处有荧光峰值。Bonner博士假设，随着年龄的增长，A2E水平的增加对RPE细胞具有细胞毒性，当次级溶酶体的内部储存量达到过高的水平，并且从这些颗粒中渗出的A2E的速度超过内质网再加工将A2E分离回颗粒的速度。诱导的RPE功能障碍是年龄相关性黄斑变性的最早和潜在可逆阶段，黄斑变性是富裕社会中最常见的致盲原因。本研究采用跨学科方法开发光谱图像分析技术，适用于从黄斑自身荧光的一系列无创光谱图像中提取A2E通路中不同荧光分子的视网膜分布图。如果这项资助成功，那么临床研究可以应用这些技术来测试光谱失衡在AMD进展中的作用理论，并基于光谱改变A2E产生和光氧化速率来评估疾病预防策略。

A2PE*H2 is a secondary irreversible photochemical product generated during periods of high alltrans- etinal generation (i.e., receptor photopigment bleaching) in the retinal photoreceptor outer segments. It has an absorption maximum at 505nm and emits fluorescence peaked at 620nm. Dr. Bonner has hypothesized that the increasing A2E levels with age are cytotoxic to the RPE cells when internal stores within the secondary lysosomes reach too high a level and the rate at which A2E leaches from these granules exceeds the rate at which endoplasmic reticulum reprocessing segregates A2E back into the granules. The induced RPE dysfunction is the earliest and potentially reversible stage of age-related macular degeneration, the most common cause of blindness in affluent societies. In this SGER a cross-disciplinary approach is taken to develop spectral image analysis techniques suitable for extracting the retinal distribution maps of the different fluorescent molecules in the A2E pathway from a series of noninvasive spectral images of macular autofluorescence. If this grant is successful, then clinical studies can be applied by these techniques to test the theory that the role of spectral imbalance in AMD progression and to evaluate disease prevention strategies based on spectrally modifying A2E production and photo-oxidation rates.