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 firstname.lastname@example.org.
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!
UIC researchers find unique organ-specific signature profiles for blood vessel cells
18.02.2020 | University of Illinois at Chicago
Remdesivir prevents MERS coronavirus disease in monkeys
14.02.2020 | NIH/National Institute of Allergy and Infectious Diseases
The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.
Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...
Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.
Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...
Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices
The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...
Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.
Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.
After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.
"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.
12.02.2020 | Event News
16.01.2020 | Event News
15.01.2020 | Event News
21.02.2020 | Physics and Astronomy
21.02.2020 | Earth Sciences
21.02.2020 | Social Sciences