Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Caring for blindness: A new protein in sight?

22.04.2015

Vasoproliferative ocular diseases are responsible for sight loss in millions of people in the industrialised countries. Many patients do not currently respond to the treatment offered, which targets a specific factor, VEGF. A team of Inserm researchers at the Vision Institute (Inserm/CNRS/Pierre and Marie Curie University), in association with a team from the Yale Cardiovascular Research Center, have demonstrated in an animal model that blocking another protein, Slit2, prevents the pathological blood vessel development that causes these diseases. This work is published in Nature Medicine.

Vasoproliferative ocular diseases are the main cause of blindness in the industrialised countries. Age-related macular degeneration (ARMD), diabetic retinopathy and retinopathy of prematurity (in newborns) are characterised by progressive involvement of the retina, the area of the eye that receives visual information and transmits it to the brain.


Growth is upward. The endothelial cells constituting the vessel walls are shown in blue and their nuclei in red. Green staining indicates the nuclei of proliferating cells, which will give rise to new vessels. Proliferating endothelial cells therefore appear yellow (green added to red).

Credit: © Alain Chédotal / Inserm

This damage is caused by abnormal growth of the blood vessels in the retina. These weakened vessels allow leakage of serum--which causes a swelling that lifts the retina--and/or blood, which leads to retinal haemorrhage.

This process involves several proteins required for normal or pathological development of the blood vessels. The action of vascular endothelial growth factor (VEGF) is a particularly decisive factor in this ocular disorder. At present, the main treatments are aimed at blocking its action by injecting inhibitors into the eye. Some patients are or become resistant to these anti-VEGF therapies.

For this reason, the team led by Alain Chédotal, in collaboration with a team led by Anne Eichmann , sought to identify new factors involved in the growth of new blood vessels, angiogenesis. They paid particular attention to Slit2.

Slit2 is a protein already known for its role in the development of neural connections. By acting on its receptors, Robo1 and Robo2, it is also involved in the development of many organs and certain cancers. The researchers therefore formulated the hypothesis that this factor might have a role in the abnormal vascularisation observed in vasoproliferative ocular diseases.

To test this postulate, the scientists inactivated Slit2 in a mouse model. They observed that ramification and growth of the retinal blood vessels were severely reduced, without any change in the stability of the pre-existing blood supply. Surprisingly, they discovered that without this protein, VEGF action was also partly reduced. By simultaneously blocking Robo1 and Robo2, they obtained the same results. They thus demonstrated that Slit2 is essential for angiogenesis in the retina.

"The success of these initial experiments led us to hope that controlling Slit2 might block the chaotic development of blood vessels in ocular diseases," explains Alain Chédotal, Inserm Research Director.

The team therefore repeated these tests in an animal model for retinopathy of prematurity. As they had suspected, the absence of Slit2 protein prevented abnormal vascularisation of the retina in these young mice.

This work suggests that therapies targeting Slit2 protein and its receptors, Robo1 and Robo2, might be beneficial for patients with vasoproliferative ocular disease, especially those who are resistant to conventional anti-VEGF therapies.

Moreover, it would be interesting to set up other studies to obtain a better understanding of the mechanism of action of Slit2 and its relationship with VEGF. This could open up new avenues for the treatment of tumours.

###

Sources

Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization. Nicolas Rama1-3,8, Alexandre Dubrac4,8, Thomas Mathivet5, Róisín-Ana Ní Chárthaigh1-3, Gael Genet4, Brunella Cristofaro5, Laurence Pibouin-Fragner5, Le Ma6, Anne Eichmann4,5,7 and Alain Chédotal1-3

1 INSERM Joint Research Unit S968, Vision Institute, Paris, France.
2 Pierre and Marie Curie University, Sorbonne Universities, Paris, France.
3 Joint Research Unit 7210, CNRS, Paris, France.
4 Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, Connecticut, USA.
5 Centre for Interdisciplinary Research in Biology (CIRB), Collège de France, Paris, France.
6 Department of Neuroscience, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
7 Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, USA.
8 These authors contributed equally to this work.

Nature Medicine, 17 April 2015

Investigator contact

Alain Chédotal
Inserm Research Director
Inserm Unit 968 "Vision Institute"
+33 (0) 1 53 46 25 15
alain.chedotal@inserm.fr

Press contact

presse@inserm.fr

Access the Inserm press room: presse-inserm.fr/en/

The press release in english : http://presse-inserm.fr/en/caring-for-blindness-a-new-protein-in-sight/18933/

In french : http://presse-inserm.fr/soigner-la-cecite-une-nouvelle-proteine-en-vue/18933/

Alain Chédotal | EurekAlert!

Further reports about: Blindness Cardiovascular Medicine blood vessels retinopathy

More articles from Health and Medicine:

nachricht The genes are not to blame
20.07.2018 | Technische Universität München

nachricht Targeting headaches and tumors with nano-submarines
20.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

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: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>