Eyeworld

22 December 2018 EW NEWS & OPINION by Liz Hillman EyeWorld Senior Staff Writer ior—actual sight—was restored. Dr. Di Polo and her team are currently conducting those experiments. In addition, they are setting up collabo- rations to test therapies in a non-hu- man primate model of glaucoma, which will be used to inform the design of a clinical trial in humans. "My hope is that we can soon come up with a smart clinical study to test the ability of insulin to restore vision in glaucoma, and hopefully move this forward for the benefit of the patients," Dr. Di Polo said. "I am grateful for the funding we received from the Glaucoma Research Foundation to carry out this promising study that might have implications for the treatment of glaucoma." Dr. Di Polo also indicated that these findings could have implica- tions for other neurodegenerative diseases with dendritic pathology such as Alzheimer's and Parkinson's disease. EW References 1. Agostinone J, et al. Insulin signalling pro- motes dendrite and synapse regeneration and restores circuit function after axonal injury. Brain. 2018;141:1963–1980. 2. Agostinone J, Di Polo A. Retinal ganglion cell dendrite pathology and synapse loss: implications for glaucoma. Prog Brain Res. 2015;220:199–216. 3. Faiq MA, Dada T. Diabetes type 4: A para- digm shift in the understanding of glaucoma, the brain specific diabetes and the candida- ture of insulin as a therapeutic agent. Curr Mol Med. 2017;17:46–59. 4. Dada T. Is glaucoma a neurodegeneration caused by central insulin resistance: diabetes type 4? J Curr Glaucoma Pract. 2017;11:77– 79. Editors' note: Dr. Di Polo has no finan- cial interests related to her comments. Contact information Di Polo: diana@dsmmedia.com selectively damage retinal ganglion cell axons. They used the syntheti- cally manufactured human insulin that is already approved and used by diabetic patients, formulating it as an eye drop for that administration. After dendritic retraction was observed in the mice, the researchers administered insulin or the control vehicle. "Vehicle-treated retinal ganglion cells displayed shrunken dendritic arbors with considerably fewer branches. In contrast, insulin administration, independently of delivery route, promoted robust retinal ganglion cell dendrite regen- eration and restored process length, arbor area and complexity," Agosti- none et al. reported. In other words, the research demonstrated the robust effect of insulin to regenerate retinal gangli- on cell dendritic arbors and restore function in these cells. Electrophys- iological assays in the form of an electroretinogram showed strong recovery of light-triggered responses after insulin treatment. As for side effects to the top- ically applied insulin, Dr. Di Polo said they did not observe redness, inflammation, or a hypoglycemic effect. One piece of information that is still missing is whether visual behav- rons that they need to make connec- tions with, so it was a nice and neat system to test this question." What led Dr. Di Polo and her coinvestigators to test insulin in this regenerative process? Dr. Di Polo cit- ed a study from her laboratory pub- lished in 2015 where they identified a key intracellular protein inside neurons known as the mammali- an target of rapamycin (mTOR), a kinase that regulates several cellular functions, including growth. 2 "We had previously demon- strated that this particular protein, mTOR, was important for the maintenance of dendrites after optic nerve injury," Dr. Di Polo said. The team then wondered, in the context of wanting to stimulate re- generation of these cells, what factor could stimulate mTOR and its com- plexes. It turns out it was insulin. The possibility of insulin playing a role in glaucoma neurodegeneration, in the context of impaired insulin signaling or insulin resistance, has also been suggested. 3,4 Dr. Di Polo and her fellow re- searchers, as described in the recent- ly published paper, tested whether a topical or systemic administration of insulin had a regenerative effect on the dendrites in a mouse model of acute optic nerve transection to New research suggests topical insulin could restore function of retinal ganglion cells damaged by glaucoma G laucoma treatment has focused largely on preven- tion, stalling progression to preserve vision and stop otherwise permanent damage to the optic nerve. However, new research presents the potential for a restorative therapy. A paper published in the journal Brain describes how insulin, in the form of an eye drop, led to regenera- tion of retinal ganglion cells (RGCs) dendrites, which receive informa- tion from photoreceptors, and resto- ration of retinal function. 1 Ten years ago, Adriana Di Polo, PhD, professor, Department of Neu- roscience, University of Montreal, Quebec, Canada, described working on axonal regeneration in the field of glaucoma and other types of neu- rodegenerative diseases. "We know that the axon is an important part of the neuron that is required for neurotransmission, a very important process," Dr. Di Polo said. "However, almost noth- ing was known about dendrites, the other side of the neurons, and their ability to regenerate after optic nerve injury. We reasoned that in order to restore the function of retinal ganglion cells and the retinal circuit, both sides of the neuron need to function for the flow of information to go through. "It started as a scientific ques- tion based on curiosity: Can den- drites regenerate?" Dr. Di Polo continued. "After all these years, we finally demonstrated that mamma- lian neurons do have the ability to regenerate, not only axons under certain circumstances, but also dendrites. Dendrites might be easier to regenerate than axons because at least in the retina, ganglion cell den- drites are closer to the target neu- Is vision restoration after glaucoma possible? " My hope is that we can soon come up with a smart clinical study to test the ability of insulin to restore vision in glaucoma, and hopefully move this forward for the benefit of the patients. " —Adriana Di Polo, PhD

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