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On October 28, 2021, Glaucoma Research Foundation (GRF) presented the virtual Weston Lecture: "New Avenues for Vision Restoration Research" featuring Adriana Di Polo, PhD, from the Department of Neuroscience at the Université de Montréal.
Watch the recorded webinar:
The lecture is introduced by Andrew Iwach, MD, Board Char of the Glaucoma Research Foundation, Dr. Jane Weston, and Thomas Brunner, GRF President and CEO.
Andrew Iwach, MD: Hello. My name is Andrew Iwach, and I am board chair of the Glaucoma Research Foundation, and the executive director of the Glaucoma Center of San Francisco. It is my honor to welcome you to the Annual Weston Family Lecture. This annual gathering showcases a nationally recognized clinician or scientist whose work notably advances our knowledge of Glaucoma. Glaucoma is the leading cause of irreversible blindness affecting approximately 4 million Americans, and more than 60 million people around the world. The Glaucoma Research Foundation's mission is to cure glaucoma, and restore vision through innovative research. Their work is possible, thanks to you, our generous donors, and dedicated volunteers who join us in this important mission. Thank you for your ongoing support.
Today's event was made possible with the remarkable support of the Weston family. Through their generosity, we have hosted this lecture for many years. It started as an in-person event, but last year it was transformed into a virtual event where we welcomed many individuals across the country, and around the world. It gave us the opportunity to highlight important advances in glaucoma research, and recognize the Weston family for their enduring friendship. Gladys and George Weston established this lecture in memory of their beloved son, Danny, who passed away of a brain tumor in 1998 at age 47. Sadly, both George and Gladys Weston are no longer with us, but their daughter, Jane, wishes to continue this lecture as a tribute to her parents, and to honor her family's passion for the work of the Glaucoma Research Foundation. We miss George and Gladys dearly, and are so very grateful for their sincere commitment to our mission to find a cure. It is now my honor to introduce their daughter, Dr. Jane Weston, to say a few words.
Dr. Jane Weston: Thank you, Dr. Iwach. This year marks a bittersweet transition for the Weston Family Glaucoma Lectureship. In 2020, we lost my dad, and last year, my mom followed leaving me to honor their memory by continuing to provide a platform that will showcase the important work of the Glaucoma Research Foundation. As many of you may know, my parents started this lectureship as a way to memorialize my brother while at the same time supporting a cause that was near and dear to my father's heart. My dad suffered from low tension glaucoma. Under the excellent, and attentive care of Dr. Iwach, my dad was able to retain his eyesight throughout his life.
And it was through his interactions with Dr. Iwach that my dad was introduced to the Glaucoma Research Foundation. It is my goal to continue the Weston family support of the Glaucoma Research Foundation in general, and to the Weston family lectureship in particular for many more years to come. Today, I'm delighted to welcome you to our lecture. As we learn more about the research into vision restoration for glaucoma patients, something we all desperately want. Thank you so much for joining me and hope to continue to be seeing you.
Thomas Brunner: Thank you, Jane, for your ongoing friendship and support. My name is Tom Brunner, and I'm the president and CEO of Glaucoma Research Foundation. And as Dr. Iwach mentioned, the Weston family of the lecture has collaborated with Glaucoma Research Foundation for many years. We are truly grateful for their commitment and for outstanding support. We miss George and Gladys dearly, and are so pleased that Jane Weston will continue the tradition of the Annual Weston Family Lecture to honor the memory of her parents, and her brother, Danny. Now it is my privilege to introduce Dr. Adriana Di Polo. Adriana is a professor in the department of neuroscience at the University of Montreal. She received her biology degree from the University of Venezuela, followed by a PhD in physiology from the University of California, Los Angeles. She then pursued post-doctoral training at the center for research in neuroscience at McGill University in Montreal.
Dr. Di Polo's main search interest is discovering the fundamental molecular mechanisms that cause retinal ganglion cell death in glaucoma. She uses this knowledge, and her background as a biologist to develop novel therapeutics for glaucoma. Dr. Di Polo has received numerous awards, and has delivered dozens of talks about her research around the world. She has served on a number of scientific advisory boards and many peer review panels, and has immensely enjoyed training, and mentoring students over the years. We are most fortunate to include Dr. Di Polo on our Shaffer Grant Advisory Committee. And in 2019, she received our Shaffer Prize for the most outstanding research project. It is now my sincere pleasure to welcome, and introduce my good friend, Dr. Adriana Di Polo.
Adriana Di Polo, PhD: Thank you so much, Tom, for the kind introduction, and for the opportunity to tell you a little bit about what we have been doing in the laboratory to find new ways to restore vision in glaucoma. I also want to send a special thanks to the Weston family for their continued support of this lecture, and commitment to glaucoma research. I don't have any conflict of interest regard the content of my presentation today. And so I want to start by reminding everyone that glaucoma is a complex disease, and there's many factors that can contribute to the development of glaucoma and vision loss. And here are just a few that we know play an important role. There could be hereditary factors. Aging, we know can contribute to the development of glaucoma. And we're all aware of the important role that intraocular pressure plays. In fact, the modulation or the management of intraocular pressure is the only treatment that we currently have for this disease, but it's not really a cure.
There could be many other stressors that also participate in the development of a glaucoma. They could be vascular or biomechanical stress, and many others that I won't have time to go into today. But the point that I want to make is that independently of the many, many factors that can contribute to the development of glaucoma, ultimately the vision loss that glaucoma patients experience comes from the death of a type of cell that is present in the retina and in the optic nerve that we call retinal ganglion cells or RGCs. And you will see this abbreviation, RGC, throughout my talk. So here I'm showing the retinal ganglion cells in red, these are very special cells because they take the information, the visual information from the retina, and send it to the brain via the optic nerve. So when these cells die in glaucoma, they cannot be replaced. And, of course, that is the reason why there is vision loss in glaucoma.
So my laboratory and many other laboratories around the world have been focused on asking two important question is the first one is, why are retinal ganglion cells more vulnerable to die in glaucoma? And the second one is, how can we use that knowledge from our research to come up with new ways to restore vision in this disease, in glaucoma, for the benefit of glaucoma patients? So I'm going to be talking about strategies that we have tested in the lab to promote a retinal ganglion cell regeneration. But before I get there, I want to make an analogy that I think it's going to make it easier for me to describe the type of work that we do. And that is the analogy between a retinal ganglion cell or RGC, which is the neuron like other neurons in the brain and a tree.
So trees do have a trunk. I mean, a first to start with the bottom, with the roots. They have roots that anchor them to the soil, and in the same way retinal ganglion cells have acts on terminals that anchor them to the brain. They establish connections with all their cells in the brain. Then trees have, of course, a trunk, which is usually a very long process. And retinal ganglion cells have axons that actually are very long as well. They form the optic nerve, which is several millimeters long in humans. Then I refer to the central trunk as this part between the trunk, and the branches in a tree, which would be the equivalent of a cell body in retinal ganglion cells. The cell body is super important because it produces energy, synthesizes proteins, and does all kinds of important functions that are necessary for the retinal ganglion cells to survive.
And then lastly, well, not lastly, but second to last, we have the branches on the tree which are the complex... that form this complex canopy depending on the variety of the tree. But interestingly enough, we also have a sort of branches in retinal ganglion cells. These are very fine, and specialized processes that emanate from the cell body that we call dendrite. And in fact, the analogy with tree branches have been recognized by the fact that we also call them dendritic branches or dendritic trees. So this is like sort of the canopy of the retinal ganglion cells. And then finally we have the leaves on the trees which are, of course, the ones responsible for transforming the energy from the sun into glucose and nutrients for the tree to survive, and be maintain over many, many years. And in a similar manner, we have synapses decorating the dendritic arbor of retinal ganglion cells.
And the synapses are very important because they take up information from other cells, and transform them into neurochemical and electrical signals that are then sent down via axons to the brain for us to be able to see. And so synapses are really the currency of communication between neurons both in the retinal optic nerve and the brain. And so I'm going to be telling you a little bit about work that has been done to try to regenerate retinal ganglion cells. And first I'm going to show you that this was a very, very... has been historically a very difficult problem in science, and in medicine. In fact, the ancient dogma of nerve regeneration told us that nerves cannot regenerate. And we can see evidence of this in documents as old as these Edwin Smith Medical Papyrus, which was discovered in Egypt. It dates between 1,920 500 BC.
And this particular case, this is one of the first medical manuscripts that were found in the world, and it gives instructions for all sorts of ailments and diseases. And this particular case that I'm showing you here is a case that concerns somebody that had a crushed vertebra in the neck, and then transected the spinal cord. So this is probably the first document that we have of reporting a spinal cord injury case, and spinal cord injury is said a nerve injury, similar to what would be an optic nerve injury in glaucoma. And the instructions from this Papyrus say that this is an ailment not to be treated. So for millennia, we thought that nerve regeneration was not something possible within the medical room. And it wasn't until the 1980s with the work of Professor Albert Aguayo at McGill University here in Montreal, in Canada.
This is where I am talking today. And in fact, I'm very proud to say that Professor Aguayo was my post doctoral supervisor many years ago. And he and his team discovered a way that they could encourage retinal ganglion cell access to regenerate. And this was a very innovative approach at the time using a peripheral nerve graft in this case was a sciatic nerve. So taken from a rat, and that is in a peripheral. So in the leg, for example, sciatic nerve graft that was attached to the injured eye as shown here, and then connected to the brain. And the most surprising result was that the retinal ganglion cells that had been injured were able to enter... the axons of these cells were able to enter the graft, and then establishing up the contacts in the brain. And this was the first time that was shown using modern techniques that neurons can regenerate axons if they are provided the right conditions to regrow.
And so since then many laboratories around the world have investigated the question of promoting axon regeneration of retinal ganglion cells. And here, because of the time limitation today, I cannot go into a lot of details, but I just want to mention some of the strategies that have been used to promote axonal regeneration of retinal ganglion cells. And these are growth factors, an activation of growth programs, also the inhibition of molecules that stop growth, so growth inhibitors. And also even controlled inflammation. So the modulation of inflammation at low levels can encourage growth. And more recently we know that electrical stimulation, and epigenetic reprogramming can also stimulate axon regeneration. Now, having said that, I want to point out that axonal regeneration, and we go back to the analogy with the tree, is really a strategies, excuse me, that have been focused on the generation of one part of the neuron or the retinal ganglion cell, which is the axon.
That would be the equivalent of the trunk in the trees. But as we discussed earlier, we need all the components of the tree and also the retinal ganglion cells for them to function properly within the circuit that is established between the retina and the brain for vision to take place. Although, it is very critical that we are able to promote axon regeneration because these will restore the optic nerve which is damaging glaucoma. My laboratory recently was interested in asking the question about what happens to dendrites because we also need to reconnect these neurons to other cells within the retina. So going back to the analogy with the leaves and the branches, one of the recent observations in these area from a number of laboratories is that interestingly enough, one of the earliest responses in glaucoma is that the retinal ganglion cells retract to the branches, they lose many of their dendritic branches, and they also lose the synopses.
So they lose the ability to connect with other cells within the retina. So putting this cells again, back into the context of the retina, you have the retinal ganglion cells down here. And we asked a very simple question, can dendrites regenerate, and go from this situation where they have retracted and disconnected from their partners to a situation where they can regrow, and reconnect with the target cells within the retina? And so today I'm going to tell you the story of insulin, which is the molecule that we have very interested in studying recently within the context of dendrite regeneration. And many of you, of course, have heard of insulin in the context of diabetes because it is the way that we can currently treat diabetes with application administration of insulin. And something that I thought would be interesting to mention is that it's already been a hundred years since the discovery of insulin by Canadians Frederick Banting, and his graduate student, Charles Best, working at the University of Toronto.
They first purified and used insulin in 1921 to treat diabetic dogs. And so the treat they demonstrated for the first time that treating diabetic dogs with insulin was a way to bring them back to health, and eliminate all the adverse effects of diabetes. So this, of course, was a major advancement in medicine, and specifically for diabetic patients. And it led to Frederick Banting winning the Nobel Prize in 1923 for this amazing discovery. But what is less known is that insulin, in addition to being this very important [inaudible 00:19:34] for the control or for the regulation of glucose, it is also important for neuronal function. So the way that insulin works is, and we can think of insulin as being a key that will fit into a perfect lock in a cell that is acting on, and we call that log the insulin receptors.
So this is a very, very good interaction between the insulin, and its receptor on the cell that will allow this cell to metabolize glucose, which is one of the primary roles of insulin. But using this same model of key log interactions, insulin can also act on neurons, which is depicted here again as in this green neuron shown here can activate a signaling pathway that is very important for the way that this neuron will, respond to information coming from other neurons, and will be part of the functional circuit. So insulin is very important for normal neuro function. In fact, when insulin signaling is compromised in any way, this will have a very negative effect on the way that this neurons function within a circuit. And we know this is the case, for example, in Alzheimer's disease, where we have some individuals that have insulin resistance, and don't have normal insulin signaling, and have very severe problems with cognition, cognitive defect, and renal function. This might play an important role in glaucoma as well.
So we decided to test the role of insulin on dendritic regeneration and reconnection of retinal ganglion cells. And so finally, I'm showing you here a real image of a retinal ganglion cells in mice that have a fluorescent marker in the retinal ganglion cells that allow us to visualize these beautiful dendritic arbors that you can see here. And these dendritic trees can be reconstructed, and presented in three dimensions. We can extract a lot of information about dendrites change in glaucoma, and how they change with treatments. And so we have a very good picture about what happens with these structures. And so we decided to use this approach in mice that had glaucoma. We can induce glaucoma in mice by increasing their intraocular pressure, which is exactly what we did, and what we found is the following.
So we induced glaucoma, and waited for there to be retraction of dendrites, and started insulin treatment, daily insulin eye drops for several days. And then look at the results in terms of the dendrites that we see without insulin, and with insulin. Here on the left you can a retinal ganglion cell, dendritic arbor that did not receive insulin where you see already that the branches are much shorter. The surface area of the cell is much smaller as well. Whereas with insulin, we observe these very exuberant regrowth of dendritic branches. And then in fact, when we measured all the parameters that were associated with insulin treatment, we found that everything that we measured, including the length of the branches, the area of the canopy of these dendritic trees, the number of branches and the complexity improved dramatically with insulin. So this was very encouraging for us because it demonstrated that insulin eye drops could improve or really, greatly promote dendritic regeneration.
Now, the next question was if dendrites are regenerating, are synopses also regenerated as well? So we looked at the synapses in the retinal ganglion cell, dendritic arbors. Here on these image to the right I'm showing you the dendrites of ganglion cells in red, and each synaptic or each synapse is shown as the little blue dot that you can see here. So we can see every single synapse on the dendritic arbor of the retinal ganglion cells. And another way to present these results is by showing the individual synaptic dots. So the synapses, each of them is like an individual white dot on a black background. And you can already see here, with a naked eye, that there is many less synaptic dots or synopses in the eyes that received no insulin compared to those that were treated with insulin. And here to the right is just a graph to show you the effect of insulin shown here in red relative to no insulin show here in gray.
And you can see there's a big of effect on the regeneration of synapses by insulin. In fact, the effect is so large that it brings the number of synapses almost to the level of what we see in animals without glaucoma shown here in white. So this was quite exciting for us because it suggested that perhaps the function of the retinal ganglion cells was also recovered. And to test this we use a method that is actually currently used in the clinic to measure retinal function after visual stimulation, it's called the electroretinogram or ERG. It is really measuring the response of the retina following light stimulation by placing electrodes near the eye, and using a visual stimulus, a light stimulation. And we obtain this type of a response. So, of course, we did this in mice not in humans.
And we focused on the response of the electroretinogram that reflects the function of retinal ganglion cells. And to make a long story short, what we found is that, again, insulin shown here in red promotes a good recovery of the response to light measured by the electroretinogram relative to those mice that did not receive insulin, but received just the saline control like a placebo, if you will, and which is shown here in blue. So this was also very good news. Now, the next step was to see whether insulin also restored visual acuity, and a light evoked visual behavior. So ideally what we would like to do is something like shown here. So we would like to be able to give the mice a test, official acuity test like the one you get when you go to the ophthalmologist to have your eyes checked or to the optometrist. But of course we're going to do that in the mice.
So we used another way to measure their acuity by placing the mice with glaucoma, and treated with insulin or without insulin in this type of chamber that has vertical lines moving in either one direction or the other. And the reflex of this mice will be to move their head in the direction that the lines are moving. And so we can actually measure the head movement as a surrogate to quantify or measure the visual acuity of this mice. So what we found is that when we carry out these tests in the presence of insulin, we found that there was an improvement in visual acuity in the mice that were treated with insulin over the ones that did not receive insulin. So together, I think it makes a very good case for insulin as a way to restore retinal, and retinal in visual behavior function.
The last piece of information that I'm going to give you regarding the role of insulin is that we also looked at how good insulin was at promoting the survival of the retinal ganglion cells within the retina. So for this, again, going back to the analogy of the forest, we counted the number of retinal ganglion cells. Imagine that each cell is represented by a tree here. And what we found is that daily insulin treatment resulted in a much larger number of trees in a forest or retinal ganglion cells in the retina and the optic nerve. And they also had a much larger canopy, they were better looking. They were looking much healthier than the ones that did not have insulin. So that told us insulin, in addition to promoting dendrite regeneration, and function restoration, it also was very good for maintaining the survival of these neurons.
I just want to leave you with a few take home messages from this work. The first one, and the most obvious one was that insulin eye drops have the ability to promote robust retinal cell, dendrite, and synaptic regeneration. That this is also a very good strategy to promote or to boost the survival of these neurons, and restore circuit function as we saw from the tests that we performed measuring these retinal function and behavior. Now I'm sure many of you are thinking, "Okay, this is very promising, and insulin already used for the treatment of diabetes. So what's next with regards to glaucoma?"
A very good question. So I should say that I am not a medical doctor, and I'm not an ophthalmologist, so I cannot and should not advise on the use of insulin for the treatment of glaucoma. But the good news is that some of my colleagues and friends that are interested in this work are preparing to carry out clinical trials with insulin. So I'm very happy to say that Doctor Jeff Goldberg at Stanford University is gearing up to start dosing some patients with insulin in the coming months, and this will be closely followed by my collaborators at the University of Montreal research hospital doctors Qianqian Wang and Younes Agoumi. So I ask everyone to be a little bit patient as these wonderful clinician scientists test for the safety, and the efficacy of insulin in glaucoma patients.
To end, I want to thank everyone in my laboratory, specifically the people that carried out this work. So these were Jessica Agostinone, a PhD student in my lab who graduated last year, and Sana El Hajji, with help from doctors Luis Alarcon-Martinez, Nicolas Belforte, Florence Dotigny. I also want to thank my collaborator, Rachel Wong, at the University of Washington with who we carried out the analysis of synaptic or synapses, synaptic changes after injury, and with insulin. And of course I couldn't leave you without acknowledging the funding sources that allow us to carry out our research. A special thanks goes to the Glaucoma Research Foundation who funded the initial phases of the role of insulin in glaucoma. And we are very thankful for their support. Thank you very much. It's a privilege for me to be here today, and I'm happy to take questions.
Tom Brunner: Well, thank you very much, Adriana. What a fascinating talk about your groundbreaking research. We do have a lot of questions for you from our attendees, and I've also got some questions. And before I get into my questions about insulin, I just want to ask you what got you interested in science and biology in the first place, and how did you begin your research in glaucoma?
Dr. Adriana Di Polo: Well, that's such a great question Tom, and funnily enough I've been thinking about that recently. What got me into biology is not the same reason that I stayed in biology in the first place. I started in biology because I was very much an outdoors person that loved to be in nature. So I thought I was going to do ecology or forestry or something like that. Little did I know that what interested me the most was cell biology, and laboratory work. That's what I found more intellectually fascinating.
And from there to working on neurons, it wasn't too much of a stretch because my uncle, Rinaldo Di Polo, was a very productive, and recognized neuroscientists who instilled in me the love of, well, a love for neuroscience, and for neurobiology really. And so I started along those lines, and then fell in love with the retina. I mean, one of those things that you can't really done very well, but I thought it was the most amazing system to study neuro degeneration. And well, then I've done everything I could to stay in the retina. And then from retinal damage to glaucoma, it was also a short distance. So that's probably... that's a path from outdoors to glaucoma research.
Tom Brunner: Well, I'm certainly glad you took that path. And I think many the people attending our webinar also are appreciative.
Dr. Adriana Di Polo: Thank you.
Tom Brunner: We're very pleased to hear that you're close to starting some clinical for trials. But one question I have, have you done any investigations relative to the occurrence of glaucoma among diabetics, for example, or... So there are a lot of people using insulin on a regular basis, and it might be interesting to know, do they have a higher level or a lower level of glaucoma? Is there information that would add encouragement about the human benefits of insulin?
Dr. Adriana Di Polo: Yes. And that's a really fantastic question. So interestingly, there is some epidemiological data suggesting that there is a correlation between type two diabetes, and the development of glaucoma. So in other words, the individuals that have type two diabetes have a higher risk of developing glaucoma. And if you think about it, it makes sense because type two diabetes is the type of the disease where there is resistance to insulin. So for some reason, insulin is not having the effect it should have on the cells even if you provide insulin or even the endogenous, well, endogenous in the... Any insulin available would not be able to trigger signaling that is required.
Dr. Adriana Di Polo: That is very interesting. And I think that it supports the hypothesis that there could be insulin resistance in glaucoma similar to Alzheimer's disease. Now, in terms of the genetic correlation, I was talking to Dr. Lu [inaudible 00:36:48] not long ago, and he told me that there hasn't been any genetic correlation between diabetes and glaucoma, but the epidemiological correlation suggests that there could be some interesting things there. And I hope other people will start looking more closely at the correlation between diabetes and glaucoma, and see whether these particular population of patients that use insulin or other drugs for diabetes like metformin or the others that could be activating a similar pathway are protected from a glaucoma.
Tom Brunner: It's very interesting. And certainly, as we know at least today, there are some 260 genes that are somehow identified related to glaucoma. And it certainly would be interesting to know if there are any... is there any crossover between some of these genes that are known to be somehow involved with glaucoma versus those that might be involved with the generation of insulin or its impact or its effectiveness or whatever. So it sounds like a great area for research.
Dr. Adriana Di Polo: I absolutely agree with you. Yes. It's a gold mine, if you will, to try to, and to put together those pieces that are missing in terms of insulin signaling in glaucoma, yes.
Tom Brunner: I have a very practical question which came in as people learned about the webinar, and that is how can patients participate in these trials. Now, I wasn't aware that there were actually trials about to get underway, but I'm sure there are people who are listening, and watching today that might want to apply. Is there a way for them to participate or for interested people to volunteer in this clinical trial or in other glaucoma clinical trials?
Dr. Adriana Di Polo: Yes, I understand. And this is a very important point. I'm very happy to provide the information that the clinical trials will take place. I do not know yet how the criteria for enrolling in these trials will be shaped in the coming months. I think it would be primarily Dr. Goldberg, and then doctors, Wang and Agoumi that will set the criteria for enrolling patients. I have some idea that at the beginning it might start with the patients locally in their clinic, their own patients, but hopefully this will expand if they're... Because the first state stage will be to test for safety of the drug. So just whether insulin eye drops are safe in the glaucoma patient's eyes, that's very important to determine. So that step is covered before we move to efficacy. So I would just tell everyone to stay tuned, and I'm sure soon there will be some information from those centers that will carry out the insulin trials about the ability to enroll or what patients will be included.
Tom Brunner: Another question was, are there particular types of glaucoma or is age a factor for example, or having other diseases at the same time, having other health issues could to effect the ability to enroll? And I think in the clinical trial language, there are the inclusion criteria, right?
Dr. Adriana Di Polo: Exactly.
Tom Brunner: Who are the people that you like to have in the trial, what their conditions are, and then the exclusion criteria who are the patients that you may not want in that early trial because of concerns about other, as you say, the safety effects and so on.
Dr. Adriana Di Polo: Yes, that's correct, Tom. I'm not a clinical trial expert that's why I wanted to... that was my disclosure here that I have committed my life to glaucoma research, but there's a point at which I have to hand it over to the experts who are the people that know how to design, and run these trials. And I think the most important thing is that we have some positive feedback or some feedback from these initial trials to then open it up to a larger base of patients that everybody could benefit from this if indeed it turns out to be something that will translate to human glaucoma, which I'm very much hoping, I think we're all hoping it will. But I think we have to wait a little bit to see what those initial studies will show.
Tom Brunner: Well, maybe just switching topics for a moment because I think I'm sure everyone is going to be watching anxiously to see how these very first tests of insulin on glaucoma patients, what they show us. But thinking about not just the maintaining the retinal ganglion cells, and maybe getting them to grow new leaves to use. I love your analogy.
Dr. Adriana Di Polo: Thank you.
Tom Brunner: But what about planting new trees? So how do you feel about the possibility of actually restoring the forest to, again, to use your analogy, if the trees have all died in a particular area? In California, we have sudden Oak death, and we lose our indigenous Oak trees. Can we put a new Oak tree in there? Could you plant new retinal ganglion cells? And what are your feelings as a scientist and researcher about how soon that might actually be possible to actually replace ganglion cells with new cells? Would you care to comment on that?
Dr. Adriana Di Polo: Yes. Thank you Tom. I love to use the analogy of trees that have completely disappeared from the forest because that's what makes the most sense like reforestation, right? I have to tell you, I'm extremely excited about the research that is going on at the moment with the reprogramming of human derived stem cells to turn them into retinal ganglion cells, and the work that is being done with transplantation and trying to understand the environment to repopulate their retina with retinal ganglion cells. It is so exciting. And I think it will take maybe a few years, but it is moving forward. And I see it because in the meetings that I'm attending, and we are organizing a workshop called restore for the replacement, and regeneration of retinal ganglion cells that will take place at ARVO together with the other organizers, and Tom Johnson at Johns Hopkins University, is one of the leaders of that initiative.
And so it shows the interest in this area to move forward, and there's a lot of collaboration to try to make it happen. I think that everything we learn will be useful in that area as well. And in fact, we were talking about insulin, and other factors that are important for the regeneration of these processes. Insulin is just one of them. There could be many others that need to be taken into consideration not just for the trees that are there, but for the ones that are coming up will be planted. So if you put a new retinal ganglion cell in the retina, this cell has to extend dendrites, and reconnect with the neurons, and extend an axon. So everything we can do to improve the ability of this young tree to survive, and thrive is something that is worthwhile implementing.
I think that this workshop that we are planning, and that will take place within the next months and follow up, actually, after ARVO for quite a while, is to set up a network where we can gather all sorts of ideas and information that allows the field to move forward as solidly and rapidly as it is possible, preserving the rigor of the science, of course. But there is a huge interest and excitement about this area because it probably will be a mixture of therapies or strategies that we will use. We will maintain the ones that are there, and make them regenerate, and add new transplant, new cells that could, as you said, fill in some of the holes that are left after degeneration.
Tom Brunner: So now here's the big question for you. If you had to make a guess, when do you think we might actually see a therapy that could restore vision, whether it's using these induced pluripotent stem cells, whether it's using endogenous cells that can make themselves into new retinal ganglion cells? Can you put a timeframe on it? I won't put any words in your mouth. What do you think?
Dr. Adriana Di Polo: That is a difficult question, I have to say, because whatever I say I could be wrong, right? Whether I'm airing on the two short or too long side. I couldn't put a time, but I think depends. If we're talking about something that can be added directly that works like insulin or some of the other strategies that are being tested out there like Vitamin B3, and other things that can sustain the existing retinal ganglion cells, or even enhancing their function. We are talking about if they work, and they prove to be effective in the clinic. We're talking about just a few years. So it could be as soon as a few years if they work. And so that's really exciting.
For retinal ganglion cell transplantation, stem cell transplantation, that I think will take a little longer because we have to figure still a few issues about many aspects of that process. So the environment that they're going to be transplanted, the transplantation itself, barriers to transplantation, and also the challenge that this new cells have to regrow axons to go through the optic nerve all the way to the nerve, all the way to the brain, and also then drives within the retina to be integrated, and reform the functional circuit. So there's a lot of steps involved in that reprogramming, and transplantation strategies, but I'm very optimistic. So I think sometime within the next 10 years, we will see a lot of progress in that respect.
Tom Brunner: Well, thank you for a very inspiring talk, and for answering our questions. And probably even more important than that, for the wonderful research you do, and for working on glaucoma. So we're just so happy to have your efforts, and your knowledge focused on this important problem. And we do hope that your extraordinary work will soon be helping patients. And I'm optimistic like you that we will be seeing that in the nearer future, and maybe in the next few years, even.
Dr. Adriana Di Polo: Thank you very much Tom.
Tom Brunner: Thank you Adriana. This webinar was recorded, and will be available on our website very soon. If we were unable to answer your questions today, please visit our website, www.glaucoma.org for more information about glaucoma, and our research programs on vision restoration. You can also download our latest edition of Understanding and Living with Glaucoma, which has the newest treatment information, and tips on working with your doctor. All our activities focused on our important mission to cure glaucoma, and restore vision through innovative research. We're incredibly indebted to our donors, our corporate partners for their ongoing investment in our work.
And now we'd like to give you a very special thank you to our dear friends, Steven and Michele Kirsch, for their unwavering partnership, and remarkable contributions toward a future free from glaucoma. They have generously offered to match every gift made between now and December 31, 2021, up to $1.5 million. Their generous gift will provide the funding for the next three-year phase of our Catalyst for Cure on vision restoration. Please "join us today": https://getinvolved.glaucoma.org/donate, and double your impact for Glaucoma Research Foundation. Every gift, no matter how small makes a difference, and we would be honored to have your support. Thank you, and see you next time.
Last reviewed on November 01, 2021