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是在视网膜光感受器外部段中高质量产生（即受体光化漂白）期间产生的二次不可逆的光化学产物。它在505nm时具有最大吸收，并在620nm处发出荧光。 Bonner博士假设，当次级溶酶体内部的内部存储量达到A2E的水平过高，而A2E从这些颗粒中浸出的速率超过了内质质量网状含量的速率，则A2E水平随着年龄的增长而对RPE细胞具有细胞毒性。诱导的RPE功能障碍是与年龄相关的黄斑变性的最早且可能可逆的阶段，这是富裕社会失明的最常见原因。在此SGER中，采用跨学科方法来开发光谱图像分析技术，适合从A2E途径中不同荧光分子的视网膜分布图从黄斑自动荧光的一系列非侵入性光谱图像中提取不同荧光分子的视网膜分布图。如果这项赠款成功，那么这些技术可以应用临床研究，以测试光谱不平衡在AMD进展中的作用并根据光谱修改A2E生产和光氧化速率来评估疾病预防策略的作用。