PHOTOCHEMISTRY OF HUMAN RETINAL LIPOFUSCIN

描述(改编自申请人的摘要)：本申请是一份建议书 研究一些发色团的光物理和光化学 存在于人视网膜脂褐素的有机可溶部分。这 包括我们在内的几个小组已经证明，萃取物在 光敏化高活性中间体，如自由基、单线态 氧气和超氧化物。将被研究的发色团吸收光在 传输到视网膜的波长区域，因此他们的 作为光敏剂的能力直接影响到光诱导的损伤 到视网膜。最初的工作集中在两个发色团，它们的结构 其中一种是人类视网膜的主要荧光成分 脂褐素和另一种可能是它的前体。他们的潜在角色是 加剧视网膜上的光氧化应激将通过以下方式确定 考察了激发态单重态和三重态的形成和命运，以及 生成的反应物种。这将通过使用两者来实现 稳态和时间合成的光化学技术，允许 这些过程的循序渐进的机制可以直接观察到。这些 材料将在模拟生物环境(胶束、 脂质体、红细胞幽灵)更接近天然 环境。这些数据还可用于定量、非侵入性 对这些生色团的活体测量。最后，本文还讨论了 这些活性中间体的形成将被记录下来，以便 确定人视网膜脂褐素中存在的其他可能化合物 潜在的光氧化剂。来自这些研究的信息可能允许 通过开发协议来减缓或停止导致 对人类视网膜的不可逆转的损害

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