MECHANISMS OF RETINAL PHOTOTOXICITY

拟议研究的长期目标是确定--和 最终控制--形成的细胞毒分子(S) 用可见光照射视网膜，引起光敏 细胞退化。视网膜光毒性的理论机制是 基于脂质过氧化的概念和脂质过氧化的形成 对光敏细胞有毒性的中间体，在某些情况下 条件，对视网膜色素上皮(RPE)，导致它们 堕落。 这项拟议研究的具体目的是(1)确定光线是否 视网膜损伤是通过光敏脂质的机制发生的 氧化；(2)使用视网膜损伤的生化标记物(即脂质 氧化中间体)以评估主要损伤位置(例如， 光感受器VS RPE)；(3)确定营养维生素E或维生素A 能够调节视网膜对光损伤的敏感性；(4) 确定脂质氧化的生化标记物是否与 视网膜变性的区域模式；(5)与单个动物相关 对光损伤的敏感性随生化水平的变化 标记物；和(6)证明特定的脂质氧化的细胞毒性。 中间体。 为达到上述目标，将维持白化病大鼠和有色大鼠。 关于含有特定水平的维生素E和A的配方饮食 曝光。冷冻干燥的视网膜切片将被显微解剖成 三个特定的层面：神经视网膜、光感受器细胞和 RPE-脉络膜。每一层的样本都将被分析维生素E， 不饱和脂肪酸和气体过氧化产物 色质联用(GC-MS)。结构分析将包括 光学和电子显微镜，以及视网膜电信号将被用于 评估视网膜功能。 随着人类视网膜组织从新鲜的尸检或手术中获得， 它将被用来开发处理小视网膜活检和 获取上述参数的数据库，以备将来可能的研究之用。 这可能是因为几乎每个人都受到亚临床光损伤的影响。 到他们的视网膜。每日累积的光损伤似乎加剧了 由于营养不足和长期暴露在光线下(即电击 照明)。这项工作试图了解的基本机制 为了更好地评估视网膜光损伤的重要性，并开放 控制它的途径，并保持视网膜健康。

The long-term objective of the proposed research is to identify--and eventually control--the cytotoxic molecule(s) that are formed upon irradiation of the retina with visible light and that cause photosensitive cells to degenerate. The theoretical mechanism of retinal phototoxicity is based on the concept of lipid peroxidation and the formation of intermediates that are toxic to the photosensitive cells and, under certain conditions, to the retinal pigment epithelium (RPE), causing them to degenerate. The specific aims of the proposed research are to (1) determine if light damage to the retina occurs by a mechanism of photosensitized lipid oxidation; (2) use biochemical markers of retinal damage (i.e., lipid oxidation intermediates) to assess primary sites of damage (e.g., photoreceptors vs RPE); (3) determine if nutritional vitamin E or vitamin A are able to modulate the sensitivity of the retina to photic injury; (4) determine if the biochemical markers of lipid oxidation correlate with regional patterns of retinal degeneration; (5) correlate individual animal variation in sensitivity to light damage with levels of biochemical markers; and (6) demonstrate the cytotoxicity of specific lipid oxidation intermediates. To accomplish the above aims, albino and pigmented rats will be maintained on formulated diets containing specific levels of vitamins E and A prior to exposure. Freeze-dried sections of retina will be microdissected into three specific layers: neural retina, photoreceptor cells, and RPE-choroid. Samples of each layer will be analyzed for vitamin E, unsaturated fatty acids, and products of peroxidation by gas chromatography-mass spectrometry (GC-MS). Structural analysis will include light and electron microscopy, and electroretinograms will be used to assess retinal function. As human retinal tissue becomes available from fresh autopsies or surgery, it will be used to develop procedures to handle small retinal biopsies and acquire a data base on the above parameters for possible future studies. It may be that virtually everyone is subjected to subclinical light damage to their retinas. Daily accumulated light damage appears to be aggravated by nutritional deficiencies and extended exposure to light (i.e., electric illumination). This work seeks to understand the basic mechanisms of retinal light damage in order to better evaluate its importance and to open routes to control it, and to preserve retinal health.