PHYSIOLOGY AND PATHOPHYSIOLOGY OF PHOTORECEPTORS

视网膜退化是导致老年人失明的主要原因 以及成千上万的年轻美国人 患有遗传性视网膜退化， 色素沉着（RP）。 光感受器退化是最终的共同途径 导致视力丧失的许多侮辱的眼睛，包括许多 视紫红质或其他光转导蛋白的突变 级联。 视网膜变性是由视杆细胞特异性 同样重要的是要理解为什么正常的锥体 光感受器也会死亡， 完全失明 我们提出了两个新的特点实验 常染色体显性视网膜色素变性的动物模型，转基因 携带变异视紫红质的猪 这份报告将回答三个重要问题。 问题：（1）P347L和P347S视紫红质突变如何改变 正常的光传导和视杆细胞信号传导(2)怎么 单细胞光反应的电生理记录比较 通过间接方法得出的相同反应， 视网膜电图（ERG）？ 本项目将记录环境资源小组的能力， 作为探测感光器功能的工具。 棒的大量损失 这些动物和RP患者体内的光感受器以某种方式杀死了 视锥光感受器也一样。 如果锥体功能可以被挽救， 人类视觉行为的实质部分将保持不变。（三） 锥状光感受器的生理病理变化是什么 与视网膜变性有关， 猪？ 在过去的十年里，人们对人类社会的认识有了巨大的进步。 生物化学和分子生物学的光转导，但很少是 光感受器的病理生理学 我们将调查 单细胞光电流与吸力电极技术， 检查整个视网膜病变过程中发生的变化， 退化和视力丧失。 几个生物物理参数的 视杆细胞和视锥细胞将在3到5个阶段进行测量， 所有的视杆细胞和一半的视锥细胞都消失了 我们亦会研究 光感受器对闪烁光的反应，这被预测为是一种 细胞健康的敏感指标。 统计分析将确定 主要和次要的影响。 我们将建立一个定量的生理 退化视网膜中光感受器功能的数据库 在疾病的相同阶段对视网膜进行ERG评估。 这 数据库将有助于判断治疗干预。

Retinal degeneration is a major cause of blindness in our elderly population as well as the tens of thousands of younger Americans afflicted with inherited retinal degenerations such as retinitis pigmentosa (RP). Photoreceptor degeneration is a final common pathway resulting in loss of vision for many insults to the eye, including many mutations of rhodopsin or other proteins of the phototransduction cascade. In retinal degenerations caused by mutations in rod-specific genes, it is equally important to comprehend why the normal cone photoreceptors also die bringing patients from night blindness to near total blindness. We propose experiments on two newly characterized animal models of autosomal dominant retinitis pigmentosa, the transgenic pig carrying mutant rhodopsin. This grant will answer three important questions: (1) How do the P347L and P347S rhodopsin mutations alter normal phototransduction and rod signaling? (2) How do electrophysiological recordings of single cell photoresponses compare to those same responses derived by indirect methods with the electroretinogram (ERG)? This project will document the ERG's capacity as a tool used to probe photoreceptor function. Massive loss of rod photoreceptors in these animals and in patients with RP somehow kills the cone photoreceptors as well. If cone function could be rescued, a substantial portion of human visual behavior would remain intact. (3) What are the pathologic changes in the physiology of cone photoreceptors associated with retinal degeneration due to rhodopsin mutations in the pig? The past decade has seen tremendous advances in the understanding of the biochemistry and molecular biology of phototransduction, yet little is known about photoreceptors pathophysiology. We will investigate the single cell photocurrents with the suction electrode technique to examine the changes that take place throughout the course of the retinal degeneration and loss of vision. Several biophysical parameters of the rods and cones will be measured at 3 to 5 stages over a period in which all the rods and half the cones are lost. We will also examine the photoreceptor responses to flickering light which is predicted to be a sensitive indicator of cell health. Statistical analyses will determine major and minor effects. We will establish a quantitative physiological database for photoreceptor function in a degenerating retina coordinated with ERG evaluations of the retina at the same stages of disease. This data base will be useful in judging therapeutic intervention.