Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Defect in retinal computation linked to congenital nystagmus

06.01.2016

Researchers of Friedrich Miescher Institute for Biomedical Research (FMI) and ETH Zurich implicate a clearly defined neuron type and its circuit in the retina in the pathophysiology of idiopathic congenital nystagmus. In a mouse model of the disease, which shows similar clinical symptoms as patients, a defect in starburst cells elicited by dysfunctional FRMD7 leads to the loss of the horizontal optokinetic reflex.

The eyes of children with idiopathic congenital nystagmus involuntarily move from left to right and back again. Due to this back and forth movement, their vision is severely impaired, some of them are legally blind.


“It was striking to see how we totally lost signal in the horizontal direction in the absence of FRMD7,” commented Michele Fiscella, Postdoctoral Fellow at the FMI and D-BSSE.

In these children, the horizontal optokinetic reflex that usually helps us to hold our gaze steady is lost. In about 70% of the cases the culprit has been identified: a gene sitting on the X chromosome called FRMD7. However, how a defect in this gene leads to the disease has remained unknown.

This is where the work from the group of Botond Roska, Senior group leader at the FMI and Professor at the University of Basel, offers valuable new insights. As they published in Neuron, they showed in mice that the lack of functional FRMD7 causes the loss of the horizontal optokinetic reflex.

More specifically, they could show that the absence of FRMD7 impairs the function of one clearly defined cell type in the retina, the starburst amacrine cells. Starburst amacrine cells are interneurons that asymmetrically inhibit ganglion cells depending on the direction of the movement of an object or the entire scene.

These results were made possible thanks to a microelectronic chip from the group of Andreas Hierlemann from the Department of Biosystems Science and Engineering (D-BSSE) of the ETH Zurich. This high-density array allowed the neurobiologists to measure the electrical signal of thousands of ganglion cells simultaneously, as the retina processed the movement of objects.

“It was striking to see how we totally lost signal in the horizontal direction in the absence of FRMD7,” commented Michele Fiscella, one of the first authors of the publication. “We think that FRMD7 is involved in establishing the asymmetric connections between starburst amacrine cells and ganglion cells, a developmental step occurring early after birth,” said Antonia Drinnenberg, another first author.

With these results, the neurobiologists were for the first time able to implicate a clearly defined neuron type in the pathophysiology of a neurological disease. “To my knowledge this is the first time that we can link a disease to a defect in neurocomputation,” commented Keisuke Yonehara, the lead author of the paper.

To further validate whether dysfunction of FRMD7 in starburst cells could also cause the lack of horizontal reflex in congenital nystagmus in humans, the scientists compared the disease symptoms in patients and in mice lacking FRMD7. “Patients were able to voluntarily move their eyes horizontally, so horizontal eye movement as such was not impaired,” explained Roska, “In addition, the vertical optokinetic reflex was not affected. And since the neuronal pathways controlling the reflex is conserved in mammals, we believe that also in humans the loss of the horizontal reflex is, at least partly, due to the loss of FRMD7 in starburst cells.”

The scientists now have a valuable mouse model at hand that clearly mirrors a symptom of the human disease, and a molecular entry point, FRMD7 in starburst cells, to further probe into the molecular mechanisms of the disease.

Original publication

Yonehara K*, Fiscella M*, Drinnenberg A*, Esposti F, Trenholm S, Krol J, Franke F, Gross Scherf B, Kusnyerik A, Müller J, Szabo A, Jüttner J, Cordoba F, Police Reddy A, Németh J, Nagy ZZ, Munier F, Hierlemann A, Roska B. (2015) Congenital nystagmus gene FRMD7 is necessary for establishing a neuronal circuit asymmetry for direction selectivity. Neuron,
* These authors contributed equally to this work

Weitere Informationen:

http://www.fmi.ch/news/releases/articles/roska.160106.html

Peter Rüegg | ETH Zürich
Further information:
http://www.ethz.ch

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>