PGC-1 coactivators in photoreceptor development and survival

总结 光感受器（PR）退化是全球失明的主要原因， 仍然知之甚少。PR退化的主要原因被认为是 由活性氧（ROS）引起的损伤。公关也是一些最 高代谢细胞在体内，这种高有氧代谢是一个强大的 ROS的来源PR如何发展如此高的有氧能力，以及PR如何平衡 这种具有过量ROS的能力是未知的。我们在这里提出测试的假设 1）PR线粒体代谢的显著发育增加， 在出生后的发展是由转录辅激活因子PGC介导的， 1 α和β，已知其他线粒体代谢的有效调节剂， PGC-1 α和β同时调节抗ROS程序， 可以用来减缓PR退化我们将用新的方法来检验这些假设。 遗传小鼠模型，并与国家的最先进的方法，基因传递到 眼睛这些研究的成功可能为治疗性干预开辟新的途径， 这些毁灭性的疾病。

SUMMARY Photoreceptor (PR) degeneration is a leading cause of blindness worldwide, and remains poorly understood. A leading cause of PR degeneration is thought to be damage instilled by reactive oxygen species (ROS). PRs are also some of the most highly metabolic cells in the body, and this high aerobic metabolism is a strong source of ROS. How PRs develop such high aerobic capacity, and how PRs balance this capacity with excess ROS, is not known. We propose here to test the hypotheses that 1) the dramatic developmental increase in PR mitochondrial metabolism seen during post-natal development is mediated by the transcriptional coactivators PGC- 1alpha and beta, known potent regulators of mitochondrial metabolism in other cells; and 2) PGC-1alpha and beta simultaneously regulate an anti-ROS program that can be usurped to slow PR degeneration. We will test these hypotheses with novel genetic mouse models, and with state-of-the-art approaches for gene delivery to the eye. Success in these studies may open new avenues for therapeutic intervention in these devastating diseases.