Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 10; pp. 4045 - 4050
• Main Authors: Welsbie, Derek S., Yang, Zhiyong, Ge, Yan, Mitchell, Katherine L., Zhou, Xinrong, Martin, Scott E., Berlinicke, Cynthia A., Hackler, Laszlo, Fuller, John, Fu, Jie, Cao, Li-hui, Han, Bing, Auld, Douglas, Xue, Tian, Hirai, Syu-ichi, Germain, Lucie, Simard-Bisson, Caroline, Blouin, Richard, Nguyen, Judy V., Davis, Chung-ha O., Enke, Raymond A., Boye, Sanford L., Merbs, Shannath L., Marsh-Armstrong, Nicholas, Hauswirth, William W., DiAntonio, Aaron, Nickells, Robert W., Inglese, James, Hanes, Justin, Yau, King-Wai, Quigley, Harry A., Zack, Donald J.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 05.03.2013; National Acad Sciences
• Subjects: animal models; Animals; Apoptosis; Axons; Biological Sciences; blindness; Cell death; Cell Death - genetics; Cell Death - physiology; Cell Survival - drug effects; Cell Survival - genetics; Cell Survival - physiology; Cells; Cells, Cultured; Disease Models, Animal; Down-Regulation; drugs; Eyes; Ganglia; Glaucoma; Glaucoma - drug therapy; Glaucoma - etiology; Humans; Kinases; leucine zipper; Male; MAP Kinase Kinase Kinases - antagonists & inhibitors; MAP Kinase Kinase Kinases - genetics; MAP Kinase Kinase Kinases - physiology; Mice; mitogen-activated protein kinase; Mortality; Neurons; Optic nerve; Optic Nerve Diseases - etiology; Optic Nerve Diseases - pathology; Optic Nerve Injuries - drug therapy; Optic Nerve Injuries - enzymology; Optic Nerve Injuries - pathology; peripheral nervous system diseases; Physical trauma; Piperazines - pharmacology; Protein Kinase Inhibitors - pharmacology; Rats; Rats, Wistar; Retina; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - enzymology; Retinal Ganglion Cells - pathology; RNA Interference; Rodents; screening; Signal Transduction; Small interfering RNA; Up-Regulation; vision

Glaucoma, a major cause of blindness worldwide, is a neurodegenerative optic neuropathy in which vision loss is caused by loss of retinal ganglion cells (RGCs). To better define the pathways mediating RGC death and identify targets for the development of neuroprotective drugs, we developed a high-th...