Slowing down glaucoma and other neurodegenerative diseases

Jessica Agostinone and Adriana Di Polo

Jessica Agostinone and Adriana Di Polo

Major discovery at the CRCHUM: reestablishing communication between neurons to improve vision.

Neuroscience researcher Dr. Adriana Di Polo, Ph. D., and her team at the University of Montreal Hospital Research Centre (CRCHUM) in Canada, have made a major breakthrough in the treatment of glaucoma. Their findings could also be applicable to other neurodegenerative conditions, notably Alzheimer’s disease. The results have just been published in the prestigious British scientific journal Brain, an Oxford University Press publication.

Glaucoma affects over sixty million people in the world. This degenerative disease of the optic nerve is the leading cause of irreversible blindness worldwide. Increased ocular pressure is a major risk factor in the development of glaucoma. At the outset, people with glaucoma are unaware that they are affected because the disease does not cause vision problems during the early stages. However, ocular hypertension causes fast shrinkage of the dendrites, the fine and long projections that carry neural information from synapses to cell bodies, thus impairing retinal function.

“We discovered that the neurons of the retina have the ability to regenerate their dendrites after damage to the optic nerve, which was not known before,” stated Di Polo, the study’s senior author. “Our study shows that insulin, delivered via eye drops, promotes dendrite and synapse regeneration thus restoring the communication between neurons and retinal function. This discovery paves the way for new therapeutic strategies to restore the sight of glaucoma patients,” she added.

In recent decades, research has focused mostly on the protection and regeneration of axons, the fibers that conduct nerve information, while dendrites have been largely overlooked. “Thanks to our breakthrough, we now know that dendrites are impaired very early in neurodegenerative diseases such as Alzheimer’s disease or glaucoma. There is a real need to regenerate these structures to turn the situation around so that the neurons can once again do their work to transmit information,” commented Jessica Agostinone, the study’s first author and a Ph. D. student at the Université de Montréal under the supervision of researcher and Professor Di Polo.

The results of this study are promising for the development of new therapeutic strategies, in addition to providing a better understanding of the molecular mechanisms involved in neurodegenerative disorders related to ageing, such as glaucoma and Alzheimer’s disease.

Di Polo’s team is now studying the possibility of developing an insulin-mimetic analogue, (i.e. molecules capable of reproducing the regenerative effect of insulin) as well as gene therapies that would make it possible to treat neurodegenerative diseases. Insulin is already used by humans and has low toxicity, given that this is a medication already approved by Health Canada, this treatment could be tested in clinical trials more quickly than for other research programs.

The study by Agostinone, Di Polo and other collaborators was published on June 21, 2018, in the journal Brain. The research was carried out in collaboration with Dr. Rachel Wong, a professor at the University of Washington. Funding for the study was provided by the Canadian Institutes of Health Research (CIHR) and by the Glaucoma Research Foundation (San Francisco, USA).


Original Research Article:

Agostinone J, Alarcon-Martinez L, Gamlin C, Yu WQ, Wong ROL, Di Polo A. Insulin signalling promotes dendrite and synapse regeneration and restores circuit function after axonal injury. Brain. 2018 Jul 1;141(7):1963-1980. doi:10.1093/brain/awy142. To read the full article:


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CHUM and CRCHUM: Jacinthe Ouellette, media relations

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