Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Defect in retinal computation linked to congenital nystagmus


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:

Peter Rüegg | ETH Zürich
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>