SGER: Image Analysis Mapping of A2E Retinal Molecular Pathway

SGER：A2E 视网膜分子通路的图像分析图谱

• 批准号: 0805001
• 负责人: Wojciech Czaja
• 金额: $ 8.5万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0805001&HistoricalAwards=false
• 关键词: SGER; Image; Analysis; Mapping; A2E

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.

A2PE*H2是在高全反式缩醛生成期间产生的次级不可逆光化学产物（即，受体色素漂白）。它在505nm处有最大吸收，在620nm处有荧光峰。Bonner博士假设，当次级溶酶体内的内部储存达到过高水平时，随着年龄增加的A2E水平对RPE细胞具有细胞毒性，并且A2E从这些颗粒中浸出的速率超过内质网再加工将A2E分离回颗粒中的速率。诱发的RPE功能障碍是年龄相关性黄斑变性的最早期和潜在可逆阶段，年龄相关性黄斑变性是富裕社会中最常见的失明原因。在这个SGER的一个跨学科的方法是采取开发光谱图像分析技术，适用于提取的视网膜分布图的不同荧光分子在A2E途径从一系列的非侵入性光谱图像的黄斑自体荧光。如果这项资助获得成功，那么这些技术可以应用于临床研究，以测试光谱不平衡在AMD进展中的作用的理论，并评估基于光谱改变A2E产生和光氧化速率的疾病预防策略。