RHODOPSIN & AGE RELATED MACULAR DEGENERATION

视紫红质的3D结构变得相当清晰，这是由于来自 各种研究。具有固定的顺式-11，12- 双键显示发色团的C-4靠近中间， 螺旋F.这种光交联将与其他中间体重复 沿着转导途径靠近螺旋F的中部。这张照片- 将与其它中间体沿着 使用类似的光标记的类似物，没有固定的 11，12-双键第一个中间体是视紫红质， 需要在-196摄氏度下进行光活化， 在后续阶段中的视紫红质中间体的分析将不 样本;然而，这个过程将导致通用方法， 光交联研究。在这些3D研究中，我们 将决定发色团C-6-s周围的绝对扭曲感 和C-12-s键通过掺入对映体的视黄醛与 预定的构象。初步研究也将继续进行， 调查鲜为人知但有据可查的 漂白适应现象。所有相关的黑暗活动- 通过时间分辨差分CD和 生物化学研究将得到解决。 视网膜相关性黄斑变性（AMD）是视网膜病变患者失明的主要原因。 不存在补救措施; CA。1.7数百万美国人视力受损 AMD的。这种疾病涉及黄斑的损伤或破裂， 视网膜上负责清晰视觉的小区域。随着年龄的增长， 荧光发色团聚集在视网膜色素颗粒中 上皮（RPE）细胞。有可能这些色素吸收光子 在可见光范围内，导致光致损伤。两种荧光 存在于颗粒中的化合物已经被表征;它们被命名为 A2 E和iso-A2 E，因为它们由两个维生素A分子组成 醛（视黄醛）和一分子乙醇胺。这些化合物 在70和80岁的眼睛中存在，但在胎儿眼中不存在。洗涤剂- 这些分子的楔形结构使它们成为强有力的候选者 参与AMD。A2 E和RPE的生物合成及其光毒性 细胞，抗A2 E抗体的制备，以及A2 E对 将研究RPE功能。反AMD原则声称是 目前在越橘也在研究中。在确定了A2 E的作用之后， AMD的治疗可能涉及消除细胞A2 E以及 防止其形成。

The 3D structure of rhodopsin is becoming quite clear due to input from various studies. A photoaffinity labeled analog with a fixed cis-11,12- double bond has shown that C-4 of the chromophore is near the middle of helix F. This photo-crosslinking will be repeated with other intermediates along the transduction pathway is near the middle of helix F. This photo- crosslinking will be repeated with other intermediates along the transduction pathway using a similar photolabeled analog without the fixed 11,12-double bond. The first intermediate will be bathorhodopsin which requires photo-activation to be performed at -196 degrees Celsius and the analysis of rhodopsin intermediates in subsequent stages will not be sample; however, this procedure will lead to general methods facilitating photo-crosslinking studies. In connection with these 3D investigations, we will determine the absolute sense of twist around the chromophoric C-6-s and C-12-s bonds by incorporation of enantiomeric retinal with predetermined conformations. Preliminary studies will also be continued to investigate the origin of the little understood but well-documented phenomenon of bleaching adaptation. The related dark-activity of all- trans-retinal/opsin mixtures by time-resolved difference CD and biochemical studies will be addressed. Age-related macular degeneration (AMD) is a major cause of blindness of which no remedy exists; ca. 1.7 million Americans have impaired vision from AMD. This disease involves the damage or breakdown of the macula, a small area of the retina responsible for sharp vision. With age, fluorescent chromophores accumulate in granules of retinal pigment epithelial (RPE) cells. It is possible that these pigments absorb photons in the visible range leading to light-induced damage. Two fluorescent compounds present in the granules have been characterized; they are named A2E and iso-A2E because they consist of two molecules of vitamin A aldehyde (retinal) and one molecule of ethanolamine. These compounds are present in 70 and 80 year old eyes, but not in fetal eyes. The detergent- like wedge-shaped structure of these molecules make them strong candidates for involvement in AMD. The biosynthesis and phototoxicity of A2E and RPE cells, the preparation of antibodies against A2E, and the effect of A2E on RPE function will be investigated. The anti-AMD principle(s) claimed to be present in bilberry is also under study. After defining the role of A2E in AMD, a treatment may involve the elimination of cellular A2E as well as the prevention of its formation.