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!
Correct connections are crucial
26.06.2017 | Charité - Universitätsmedizin Berlin
One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
27.06.2017 | Power and Electrical Engineering
27.06.2017 | Information Technology
27.06.2017 | Physics and Astronomy