GA is an untreatable condition that causes blindness in millions of individuals due to death of retinal pigmented epithelial cells. The paper, "DICER1 loss and Alu RNA Induce Age-Related Macular Degeneration via the NLRP3 Inflammasome and MyD88," was published in the April 26 online edition of the premier journal Cell.
Ambati, professor of physiology, and professor and vice chair of ophthalmology and visual sciences at UK, is a leader in the field of macular degeneration research. Previous research from the Ambati laboratory published in the journal Nature showed that in human eyes with geographic atrophy there is a deficiency of the enzyme DICER1, leading to accumulation of toxic Alu RNA molecules in the retinal pigmented epithelium. The Cell paper shows that when these RNAs build up in the eye they trigger activation of an immune complex known as the NLRP3 inflammasome. In turn, this leads to the production of a molecule known as IL-18, which causes death of retinal pigmented epithelial cells and vision loss by activating a critical protein known as MyD88.
Importantly, Ambati and colleagues found evidence that activity of the inflammasome, IL-18, and MyD88 were all increased in human eyes with GA. They then showed that blocking any of these components could prevent retinal degeneration in multiple disease models. The researchers are excited that blocking these pathways could herald a new potential therapy for GA, for which there is no approved treatment.
Ambati is working with iVeena Pharmaceuticals, Inc. of Salt Lake City to commercialize therapies for geographic atrophy. iVeena can be contacted at email@example.com.
Authors on the paper include Ambati as well as Valeria Tarallo, Yoshio Hirano, Bradley D. Gelfand, Sami Dridi, Nagaraj Kerur, Younghee Kim, Won Gil Cho, Hiroki Kaneko, Benjamin J. Fowler, Sasha Bogdonaovich, Romulo J.C. Albuquerque, Judi Z. Baffi and Mark E. Kleinman, all of the UK Department of Opthalmology and Visual Science. Additional authors include: William W. Hauswirth and Vince A. Chiodo of the University of Florida; Jennifer F. Kugel, James A. Goodrich and Steven L. Ponicsan of the University of Colorado; Gautaum Chaudhuri of Meharry Medical College; Michael P. Murphy of the MRC Mitochondrial biology Unit; Joshua L. Dunaief of the University of Pennsylvania; Balamurali K. Ambati of the University of Utah and the Veterans Affairs Salt Lake City Healthcare System; Yuichiro Ogura of the Nagoya City University Graduate School of Medical Sciences, Japan; Jae Wook Yoo and Dong-ki Lee of Sungkyunkwan University, Korea; Patrick Provost of Université Laval, Quebec; David R. Hinton of the University of Southern California; and Gabriel Nunez of the University of Michigan Medical School.
Ambati is also the Dr. E. Vernon and Eloise C. Smith Endowed Chair in Macular Degeneration Research.
This research was supported by the National Eye Institute, the Doris Duke Charitable Foundation, the Burroughs Wellcome Fund, and Research to Prevent Blindness.
Allison Elliott | EurekAlert!
Purdue cancer identity technology makes it easier to find a tumor's 'address'
16.11.2018 | Purdue University
Microgel powder fights infection and helps wounds heal
14.11.2018 | Michigan Technological University
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
16.11.2018 | Health and Medicine
16.11.2018 | Life Sciences
16.11.2018 | Life Sciences