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A French research team from INSERM, led by Alvaro Rendon, CNRS research
director (Institut de la Vision, Hôpital Saint-Antoine - Inserm
U-592), in partnership with an Israeli team (Weizmann Institute) and a
German team (University of Leipzig), have just discovered the role of
dystrophin gene product Dp71 on the balance of the central nervous system
and the retina, in particular. Dystrophin gene product Dp71 is one of
the seven proteins coding for the DMD gene (responsible for Duchenne muscular
dystrophy). The absence of this protein, the most abundant in the central
nervous system, causes the retina to be more vulnerable to vascular disorders,
especially to an ischaemia retinae (diminished blood supply in the retina
due to failure of the arterial circulation). The normal functioning of
ganglionic neurons(1) is then disturbed, preventing the
transmission of visual information from the eye to the brain. The results
of these studies, financed in large part by the AFM (French Muscular Dystrophy
Association), thanks to donations from the Telethon, are published in
the July 1, 2003, issue of the international journal Human Molecular
Genetics. This research was also supported by the ADRET(2)
of Alsace, the FAF(3) and Retina France.
Duchenne muscular dystrophy,
resulting from the lack of dystrophin coding for the DMD gene located
on chromosome X, is characterized by progressive muscular degeneration,
often accompanied by non-progressive disorders of the central nervous
system. The INSERM team, led by Alvaro Rendon of the laboratory directed
by José Sahel, discovered that some of these central nervous system
disorders are caused by the lack of another protein coding for the DMD
gene, dystrophin gene product Dp71. This research was conducted on a Dp71-null
mouse model, produced by the Weizmann Institute team (Professors Yaffe
and Nudel) in Israel.
This protein is the most abundant in the central nervous system and especially
in the retina. Its deficiency appears to lead to the impaired clustering
of two other proteins necessary for its balance: the potassium channel
(Kir4.1) and the water pore aquaporin (AQP4). Since these proteins must
be localized in a specific spot in order to function normally, the entire
physiological balance of the retina is therefore disturbed.
The research team demonstrated that in the case of mice, the Dp71 protein
is localized exclusively in the Müller glial cell, located in the
retina and absolutely necessary to the normal functioning of ganglionic
neurons. In the event of an ischaemia, blood circulation is diminished
and may even be interrupted, leading to a modification of physiological
constants. Müller glial cells therefore play a very important role:
they are responsible for reestablishing the disturbed physiological balance
within the retina. These disorders are found in serious pathologies such
as diabetic retinopathy and glaucoma.
In the same way that dystrophin contributes to the stabilization of ionic
channels and signaling proteins in the muscles, the Dp71 protein is responsible
for the precise localization of ionic and aqueous channels in the Müller
glial cell in the retina.
The discovery of the major role of the Dp71 protein in the aqueous and
ionic balance of the retina is of utmost importance. It could lead to
new therapeutic approaches to ischaemia of the brain and the retina. Improved
knowledge of its role will also contribute to a better understanding of
other vision disorders.
(1) Ganglionic
neurons carry visual information from the eye to the brain.
(2) Association for the development of research on the
regeneration of the retina and its transplantation.
(3)Fédération des Aveugles et Handicapés
Visuels de France (French Federation of the Blind and Visually Impaired).
For more information
“Targeted inactivation of dystrophin gene product Dp71: phenotypic
impact in mouse retina”
Cécile Dalloz, Rachel Sarig, Patrice Fort, David Yaffe, Agnès
Bordais, Thomas Pannicke, Jens Grosche, Dominique Mornet, Andreas Reichenbach,
José Sahel, Uri Nudel and Alvaro Rendon. Human Molecular Genetics,
vol. 12. n° 13, pages 1543-1554, 2003.
Researcher
contact:
Alvaro Rendon
Inserm - U592 - Laboratoire de Physiopathologie Cellulaire et Moléculaire
de la Rétine
Hôpital Saint-Antoine, Bâtiment Kourilsky
184 rue du Faubourg Saint-Antoine
75571 Paris Cedex 12
Tel: + 33 (0)1 49 28 46 04
e-mail: rendon@st-antoine.inserm.fr
Press contacts:
Emmanuelle Guiraud / Estelle Assaf
AFM (French Muscular Dystrophy Association)
Tel: +33 (0)1 69 47 28 28
e-mail: essaf@afm.genethon.fr
Céline Goupil – Inserm
Tel: +33 (0)1 44 23 60 73
e-mail: presse@tolbiac.inserm.fr
Patients' association:
Maladies Rares Info Service (Rare Diseases Information Service)
Tel: +33 (0)8 10 63 19 20
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