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Glaucoma Research Foundation Grant Leads to Major Breakthrough in Neuron Regeneration

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Study indicates treatment using insulin may restore vision in
glaucoma patients

Glaucoma
Research Foundation
, a national non-profit organization dedicated to
finding a cure for glaucoma, today announced a team of neuroscience
researchers, led by Adriana
Di Polo, PhD
, at University of Montreal, have made a major
breakthrough in the treatment of glaucoma. The research, which was made
possible by a Glaucoma Research Foundation Shaffer Grant, could also be
applicable to other neurodegenerative diseases, including Alzheimer's
disease.

Glaucoma is the second leading cause of blindness in the world, and
vision loss from glaucoma is irreversible. Currently there is no cure,
and everyone is at risk for developing this blinding disease. It is
estimated that by 2020, 80 million people worldwide will have glaucoma.
Loss of vision in glaucoma results from the death of retinal ganglion
cells (RGCs), which are composed of axons and dendrites. A crucial step
towards vision repair in glaucoma is to promote damaged RGCs to
regenerate not only axons, but also dendrites to successfully reconnect
with their synaptic partners in the retina.

Much of glaucoma research focuses on neuroprotection, but Dr. Di Polo's
team wanted to study whether the retinal neurons would regenerate with
treatment after optic nerve damage. The research team first waited for
dendritic retraction and loss of vision in a mouse model of glaucoma,
then administered insulin before testing for regeneration of retinal
neurons. They administered insulin via two methods, eye drops and
systemic injections, and observed that the dendrites and synapses
regenerated. Remarkably, the treatment was able to not only preserve,
but also to restore retinal function.

The research, published in the July 2018 issue of the prestigious Oxford
University Press journal Brain,
was authored by Jessica Agostinone, Luis Alarcon-Martinez, Clare Gamlin,
Wan-Qing Yu, Rachel O. L. Wong, and Adriana Di Polo1. The
article was also selected for Editorial commentary in Brain2.
It built on 10 years of prior research by Dr. Di Polo's team, including
a study that demonstrated that molecules activated by insulin play a
major role in the regrowth and stability of the dendrites. The data
support the rationale for using insulin
and its analogues as
pro-regenerative therapeutic targets to counter progressive RGC
neurodegeneration and vision loss in glaucoma.

"An exciting aspect of our findings is that insulin is already in
clinical use. It's a commonly used drug with a long history of safety
and efficacy in humans. Previous work demonstrated that insulin eye
drops, applied at doses much higher than in our study, were innocuous
and produced no detectable clinical toxicity when applied topically in
healthy humans," said Dr. Di Polo. "We are so grateful that the Glaucoma
Research Foundation supports teams like ours that want to explore new
ideas. We thank the Glaucoma Research Foundation for its support that
helped us accomplish our research goals and bring hope to glaucoma
patients everywhere."

Dr. Di Polo and her team are now in discussion with clinical
collaborators to design a first-in-kind trial to test this regenerative
approach in glaucoma patients.

"The research from Dr. Di Polo's team at University of Montreal is
significant in that it demonstrated regeneration of the dendrites in the
retinal ganglion cells, and also because it uses insulin, which has been
shown to be safe for clinical use," said Thomas M. Brunner, president
and CEO, Glaucoma Research Foundation. "Glaucoma Research Foundation is
thrilled to have funded this team of innovative researchers, and we are
optimistic that it has brought us one step closer to a cure for
glaucoma."

About Glaucoma Research Foundation

Glaucoma Research Foundation (GRF) is a national non-profit organization
dedicated to finding a cure for glaucoma. For 40 years, Glaucoma
Research Foundation has worked to advance sight-saving research and
provide essential educational resources for patients. It funds critical
research into glaucoma treatment, vision restoration, and a cure for
glaucoma. It also is the leading source of information for glaucoma
patients and their families. For more information, visit www.glaucoma.org.

1 Insulin signalling promotes dendrite and synapse
regeneration and restores circuit function after axonal injury. Jessica
Agostinone, Luis Alarcon-Martinez, Clare Gamlin, Wan-Qing Yu, Rachel O L
Wong, and Adriana Di Polo, Brain, Volume 141, Issue 7, 1 July 2018,
Pages 1963–1980, https://doi.org/10.1093/brain/awy142

2 Mammalian dendritic regrowth: a new perspective on neural
repair. Sheri Peterson and Larry Benowitz, Brain, Volume 141, Issue 7, 1
July 2018, Pages 1888-1899, https://academic.oup.com/brain/article-abstract/141/7/1891/5045310?redirectedFrom=fulltext

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