Cytokine Regulation of Photoreceptor Gene Expression

6.项目总结/摘要 遗传性视网膜变性的特征是视网膜神经元（最常见的是光感受器）的丧失。 Retnet数据库中的150多个基因已被证明会导致某种形式的视网膜变性 当基因突变时，这表明这些疾病有很强的遗传成分。通常情况下，失明 先天性的，但延迟到第五，第六，或第七个十年的生活。基因突变在受孕时就存在 然而光感受器在有害突变的情况下存活并发挥作用数十年。这种现象 表明视网膜有一个内源性的自我保护系统。通过学习这个系统 内源性保护功能，我们也许能够利用它来进一步延迟甚至预防失明 全部这个项目的目的是进一步了解我们的内源性机制， 保护视网膜光感受器免于细胞死亡。本提案的四个目标是： PIM激酶是光感受器的诱导保护所必需的（目的1）。确定是否诱导 视网膜光感受器的保护是通过增加线粒体的生物合成或 线粒体修复（aim 2）。确定是否抑制线粒体生物合成或修复通过 PGC-1活性的基因突变阻止预处理诱导的保护（目的3）。测试新的细胞因子 我们开发了增强神经保护活性的药物（目的4）。

6. Project Summary/Abstract Inherited retinal degenerations are characterized by the loss of retinal neurons (most often photoreceptors). More than 150 genes in the Retnet database have been shown to cause some form of retinal degeneration when the gene is mutated, indicating a strong genetic component to these diseases. Often, blindness isn't congenital but is delayed until the 5th, 6th, or 7th decade of life. The genetic mutation is present at conception and yet photoreceptors survive and function for decades with the deleterious mutation. This phenomenon suggests that the retina has an endogenous system of self protection. By learning how this system of endogenous protection functions, we may be able to exploit it to further delay or even prevent blindness altogether. This project was designed to further our knowledge of the endogenous mechanisms by which retinal photoreceptors are protected from cell death. The four aims of this proposal will: Determine whether PIM kinases are required for induced protection of photoreceptors (aim 1). Determine whether induced protection of retinal photoreceptors is brought about through increased mitochondrial biogenesis or mitochondrial repair (aim 2). Determine whether inhibition of mitochondrial biogenesis or repair through genetic mutation of PGC-1 activity prevents preconditioning induced protection (aim 3). Test new cytokines that we developed for enhanced neuroprotective activity (aim 4).