Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Changes in the eye can predict changes in the brain

25.08.2014

Gladstone scientists show that retinal thinning can be used as an early marker for frontotemporal dementia, prior to the onset of cognitive symptoms

Researchers at the Gladstone Institutes and University of California, San Francisco have shown that a loss of cells in the retina is one of the earliest signs of frontotemporal dementia (FTD) in people with a genetic risk for the disorder—even before any changes appear in their behavior.


This is a retina cross-section from a healthy mouse showing TDP-43 staining (green), Ran staining (red), and nuclei (blue).

Credit: Dr. Michael Ward

Published today in the Journal of Experimental Medicine, the researchers, led by Gladstone investigator Li Gan, PhD and UCSF associate professor of neurology Ari Green, MD, studied a group of individuals who had a certain genetic mutation that is known to result in FTD. They discovered that before any cognitive signs of dementia were present, these individuals showed a significant thinning of the retina compared with people who did not have the gene mutation.

"This finding suggests that the retina acts as a type of 'window to the brain,'" said Dr. Gan. "Retinal degeneration was detectable in mutation carriers prior to the onset of cognitive symptoms, establishing retinal thinning as one of the earliest observable signs of familial FTD. This means that retinal thinning could be an easily measured outcome for clinical trials."

Although it is located in the eye, the retina is made up of neurons with direct connections to the brain. This means that studying the retina is one of the easiest and most accessible ways to examine and track changes in neurons.

Lead author Michael Ward, MD, PhD, a postdoctoral fellow at the Gladstone Institutes and assistant professor of neurology at UCSF, explained, "The retina may be used as a model to study the development of FTD in neurons. If we follow these patients over time, we may be able to correlate a decline in retinal thickness with disease progression. In addition, we may be able to track the effectiveness of a treatment through a simple eye examination."

The researchers also discovered new mechanisms by which cell death occurs in FTD. As with most complex neurological disorders, there are several changes in the brain that contribute to the development of FTD. In the inherited form researched in the current study, this includes a deficiency of the protein progranulin, which is tied to the mislocalization of another crucial protein, TDP-43, from the nucleus of the cell out to the cytoplasm.

However, the relationship between neurodegeneration, progranulin, and TDP-43 was previously unclear. In follow-up studies using a genetic mouse model of FTD, the scientists were able to investigate this connection for the first time in neurons from the retina. They identified a depletion of TDP-43 from the cell nuclei before any signs of neurodegeneration occurred, signifying that this loss may be a direct cause of the cell death associated with FTD.

TDP-43 levels were shown to be regulated by a third cellular protein called Ran. By increasing expression of Ran, the researchers were able to elevate TDP-43 levels in the nucleus of progranulin-deficient neurons and prevent their death.

"With these findings," said Dr. Gan, "we now not only know that retinal thinning can act as a pre-symptomatic marker of dementia, but we've also gained an understanding into the underlying mechanisms of frontotemporal dementia that could potentially lead to novel therapeutic targets."

###

This research was conducted in collaboration with scientists from the University of Alabama at Birmingham, and the University of Texas Southwestern. It was funded by the Consortium for Frontotemporal Dementia Research, Bluefield Project to Cure FTD, National Institutes of Health, UCSF Resource Allocation Program, UCSF Alzheimer's Disease Research Center, Chartrand Foundation and Clinical & Science Translational Institute, Howard Hughes Medical Institute, Alzheimer's Association, Welch Foundation, and Alzheimer's Drug Discovery Foundation.

About the Gladstone Institutes

To ensure our work does the greatest good, the Gladstone Institutes focus on conditions with profound medical, economic, and social impact—unsolved diseases of the brain, the heart, and the immune system. Affiliated with the University of California, San Francisco, Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease.

About UCSF

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy, a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences, as well as a preeminent biomedical research enterprise and two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children's Hospital San Francisco.

Dana Smith | Eurek Alert!

Further reports about: Alzheimer's FTD Gladstone Medical TDP-43 UCSF death dementia mechanisms neurons progranulin retinal

More articles from Life Sciences:

nachricht Novel 'repair system' discovered in algae may yield new tools for biotechnology
29.07.2016 | Boyce Thompson Institute

nachricht Molecular troublemakers instead of antibiotics?
29.07.2016 | Christian-Albrechts-Universität zu Kiel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Self-assembling nano inks form conductive and transparent grids during imprint

Transparent electronics devices are present in today’s thin film displays, solar cells, and touchscreens. The future will bring flexible versions of such devices. Their production requires printable materials that are transparent and remain highly conductive even when deformed. Researchers at INM – Leibniz Institute for New Materials have combined a new self-assembling nano ink with an imprint process to create flexible conductive grids with a resolution below one micrometer.

To print the grids, an ink of gold nanowires is applied to a substrate. A structured stamp is pressed on the substrate and forces the ink into a pattern. “The...

Im Focus: The Glowing Brain

A new Fraunhofer MEVIS method conveys medical interrelationships quickly and intuitively with innovative visualization technology

On the monitor, a brain spins slowly and can be examined from every angle. Suddenly, some sections start glowing, first on the side and then the entire back of...

Im Focus: Newly discovered material property may lead to high temp superconductivity

Researchers at the U.S. Department of Energy's (DOE) Ames Laboratory have discovered an unusual property of purple bronze that may point to new ways to achieve high temperature superconductivity.

While studying purple bronze, a molybdenum oxide, researchers discovered an unconventional charge density wave on its surface.

Im Focus: Mapping electromagnetic waveforms

Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.

Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...

Im Focus: Continental tug-of-war - until the rope snaps

Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases

Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2016: 7th Conference on the Art, Technology and Theory of Digital Games

29.07.2016 | Event News

GROWING IN CITIES - Interdisciplinary Perspectives on Urban Gardening

15.07.2016 | Event News

SIGGRAPH2016 Computer Graphics Interactive Techniques, 24-28 July, Anaheim, California

15.07.2016 | Event News

 
Latest News

Vortex laser offers hope for Moore's Law

29.07.2016 | Power and Electrical Engineering

Novel 'repair system' discovered in algae may yield new tools for biotechnology

29.07.2016 | Life Sciences

Clash of Realities 2016: 7th Conference on the Art, Technology and Theory of Digital Games

29.07.2016 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>