Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers track down cause of eye mobility disorder

17.04.2014

Normal development stalls in the nerves

Imagine you cannot move your eyes up, and you cannot lift your upper eyelid. You walk through life with your head tilted upward so that your eyes look straight when they are rolled down in the eye socket. Obviously, such a condition should be corrected to allow people a normal position of their head. In order to correct this condition, one would need to understand why this happens.


The image depicts mice having a normal nerve (left) as compared to an incomplete nerve, a condition resulting in permanent downward gaze in both mice and humans. Image courtesy of Jeremy Duncan.

In a paper published in the April 16 print issue of the journal Neuron, University of Iowa researchers Bernd Fritzsch and Jeremy Duncan and their colleagues at Harvard Medical School, along with investigator and corresponding author Elizabeth Engle, describe how their studies on mutated mice mimic human mutations.

It all started when Engle, a researcher at the Howard Hughes Medical Institute (HHMI), and Fritzsch, professor and departmental executive officer in the UI College of Liberal Arts and Sciences Department of Biology, began their interaction on the stimulation of eye muscles by their nerves, or “innervation,” around 20 years ago.

Approximately 10 years ago, Engle had identified the mutated genes in several patients with the eye movement disorder and subsequently developed a mouse with the same mutation she had identified in humans. However, while the effect on eye muscle innervation was comparable, there still was no clue as to why this should happen.

Fritzsch and his former biology doctoral student, Jeremy Duncan, worked with the Harvard researchers on a developmental study to find the point at which normal development of eye muscle innervations departs from the mutants. To their surprise, it happened very early in development. In fact, they found—only in mutant mice—a unique swelling in one of the nerves to the eye muscle.

More detailed analysis showed that these swellings came about because fibers extending to the eyes from the brain tried to leave the nerve as if they were already in the orbit, or eye socket. Since it happened so early, the researchers reasoned that something must be transported more effectively by this mutation to the motor neurons trying to reach the orbit and the eye muscles; something must be causing these motor neurons to assume they have already reached their target, the orbit of the eye.

To verify this enhanced function, the researchers developed another mouse that lacked the specific protein and found no defects in muscle innervation. Moreover, when they bred mice that carried malformed proteins with those that had none of these proteins, the mice developed a normal innervation.

This data provided clear evidence of what was going wrong and why, but it did not provide a clue as to the possible product that was more effectively transported in the mutant mice and, by logical extension, in humans. Further analysis revealed that breeding their mutant mice with another mutant having eye muscle innervation defects could enhance the effect of either mutation.

With this finding, they had identified the mutated protein, its enhanced function, and at least some of the likely cargo transported by this protein to allow normal innervation of eye muscles. This data provides the necessary level of understanding to design rational approaches to block the defect from developing.

Knowing what goes wrong and at what time during development can allow the problem to be corrected before it develops through proper manipulations. Engle, Fritzsch, and their collaborators currently are designing new approaches to rescue normal innervation in mice. In the future, their work may help families carrying such genetic mutations to have children with normal eye movement.

The title of the Neuron paper is “Human CFEOM1 Mutations Attenuate KIF21A Autoinhibition and Cause Oculomotor Axon Stalling.”

The research was supported by a National Institutes of Health (NIH) grant to Engle and colleague Fritzsch and HHMI funding to Engle.

Contacts

Steve Kehoe, Department of Biology, 319-335-1050

Steve Kehoe | Eurek Alert!
Further information:
http://www.uowa.edu

Further reports about: Biology Department HHMI NIH Neuron disorder eye movement eye movement disorders eyes genes movement protein proteins

More articles from Health and Medicine:

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>