Scientists have identified a double agent in the eye that, once triggered, can morph from neuron protector to neuron killer. The discovery has significant health implications since the neurons killed through this process results in vision loss and blindness.
Discovery from Université de Montreal and McGill
University’s Montreal Neurological Institute
Montreal, February, 1, 2010 – Scientists have
identified a double agent in the eye that, once triggered, can
morph from neuron protector to neuron killer. The discovery has
significant health implications since the neurons killed through
this process results in vision loss and blindness.
The findings, published in the journal Proceedings of the
National Academy of Sciences (PNAS), are collaboration between
the Université de Montreal, McGill University and the Montreal
Neurological Institute in Canada and the Université de Namur in
Belgium. The researchers show how an unusual molecule, called
proNGF, activates glial cells that normally protect neurons in the
retina and brain.
“We found that glial cells attack and kill neurons after being
triggered by proNGF,” says coauthor Dr. Philip Barker, a
neuroscientist at the Montreal Neurological Institute and a
professor at the McGill Department of Neurology and Neurosurgery.
“Since glial cells normally protect neurons, we were surprised to
find that proNGF can convert glial cells into killers that cause
neuron death in the retina.”
Coauthor Dr. Adriana Di Polo, a professor at the Université de
Montréal Department of Pathology and Cell Biology, compares the
proNGF molecule to a cell hijacker. “Before this study, we didn’t
know what physiological role the proNGF molecule played in the
eye,” she says. “We now propose that, following brain damage or
neurodegenerative diseases, proNGF alters the glial cell network to
change its function. Rather than protecting neurons, proNGF makes
the glial cells attack neurons."
Scientists must now pay more attention to the damage proNGF can
trigger. “Once retinal neurons die, they are gone forever and the
permanent loss of these cells causes blindness,” warns Dr. Di Polo.
“The next step for researchers is to explore whether proNGF signals
can be controlled", says Frédéric Lebrun-Julien, first author and a
PhD student at the Université de Montréal's Department of Pathology
and Cell Biology.
Dr. Barker concurs. “If we can block factors induced by proNGF,
we can protect neurons that would normally be lost. We think these
findings may eventually translate into clinical benefits in
diseases such as glaucoma.”
Partners in research:
The study was supported by the Canadian Institutes of Health
Research and the Fonds de Recherche en Santé du
About the study:
The paper, “ProNGF induces TNFα-dependent death of retinal ganglion
cells through a p75NTR non-cell-autonomous signaling pathway,”
published in the journal PNAS, was authored by Frédéric
Lebrun-Julien and Adriana Di Polo of the Université de Montréal;
Olivier De Backer of the Université de Namur in Belgium; David
Stellwagen, Mathieu J. Bertrand, Carlos R. Morales and Philip A.
Barker of the Montreal Neurological Institute / McGill
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