PHOTOCHEMISTRY OF HUMAN RETINAL LIPOFUSCIN

描述（改编自申请人摘要）：本申请是一项提案 研究一些发色团的光物理和光化学， 存在于人视网膜脂褐质的有机可溶部分。这 包括我们在内的几个小组已经证明， 光敏高活性中间体，如自由基，单线态 氧气和超氧化物。待研究的发色团吸收光， 波长区域，其被传输到视网膜，因此其 作为光敏剂的能力对光诱导的损伤有直接影响 到视网膜最初的工作集中在两个发色团，其结构 是已知的，其中之一是人视网膜色素的主要荧光成分， 脂褐质和另一种可能的前体。它们在以下方面的潜在作用： 视网膜上的光氧化应激的加剧将通过 研究激发单重态和三重态的形成和命运， 生成的活性物质。这将通过使用 稳态和时间合成的光化学技术， 这些过程的逐步机制可以直接观察到。这些 材料将在模型生物环境（胶束， 脂质体、红细胞血影）以更接近天然的 环境这些数据还可以允许定量的、非侵入性的 测量这些生色团在体内。最后， 将记录这些活性中间体的形成， 确定存在于人视网膜脂褐素中的其他可能的化合物， 潜在的光氧化剂。这些研究的信息可能允许 制定协议，以减缓或停止导致 对人类视网膜造成不可逆转的损伤

DESCRIPTION (Adapted from applicant's abstract): This application is a proposal to study the photophysics and photochemistry of a number of chromophores that are present in the organic soluble portion of human retinal lipofuscin. This extract has been shown by several groups including ours to be efficient at photosensitizing highly reactive intermediates such as free radicals, singlet oxygen and superoxide. The chromophores to be studied absorb light in the wavelength region that is transmitted to the retinal and therefore their ability to act as photosensitizers has a direct impact on light induced damage to the retinal. Initially the work focuses on two chromophores whose structures are known, one being the major fluorescent component of human retinal lipofuscin and the other its likely precursor. Their potential role in exacerbating photooxidative stress on the retinal will be ascertained by examining the formation and fate of excited singlet and triplet states and the resultant reactive species. This will be achieved through the use of both steady state and time resultant photochemical techniques that allow the step-by-step mechanisms of these processes to be directly observed. These materials will be studied in model biological environments (micelles, liposomes, erythrocyte ghosts) to more closely approximate the native environment. These data may also allow for quantitative, non-invasive measurements of these chromophores in vivo. Finally, action spectra for the formation of these reactive intermediates will be recorded in order to determine other possible compounds present in human retinal lipofuscin that are potential photooxidizing agents. Information from these studies may allow for the development of protocols to slow down or stop the processes that lead to irreversible damage to the human retina