Cytokine Regulation of Photoreceptor Gene Expression

6.项目摘要/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退化 当基因发生突变时，表明这些疾病有很强的遗传成分。通常，失明并不是 先天的，但被推迟到生命的第五、第六或第七个十年。基因突变是在受孕时出现的 然而，光感受器在这种有害的突变中存活了几十年并发挥了作用。这一现象 这表明视网膜有一种内源性的自我保护系统。通过学习这个系统是如何 内源性保护功能，我们也许能够利用它来进一步延缓甚至预防失明 总而言之。这个项目的设计是为了加深我们对内生机制的了解 视网膜光感受器受到保护，免于细胞死亡。这项提案的四个目标将决定： PIM激酶是光感受器诱导保护所必需的(目标1)。确定是否已诱导 视网膜光感受器的保护是通过增加线粒体的生物发生或 线粒体修复(目标2)。确定是否通过抑制线粒体的生物发生或修复 PGC-1活性的基因突变可防止预适应诱导的保护(目标3)。检测新的细胞因子 我们为增强神经保护活性而开发的药物(目标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).