Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Regenerative Medicine In Ophthalmology At The Fox Center For Vision Restoration, JOE S. SCHUMAN, MD 1 So I’m going to talk about regenerative ophthalmology and very little of what I’m talking about is my work and I’ll try to let you know who is doing what when I’m talking about specific things. But we’re going to cover a fairly wide swath as we do this. One of the most mature areas that we are doing work in is in cornea and Jim Funderburgh’s lab is really a leader in corneal stromal regeneration so Jim Funderburgh and Yiquin Du who is in the audience you’re going to hear from I think next, discovered a stem cell that is for the corneal stroma and basically that stem cell can rebuild cloudy corneas in mice. So if you take a mouse that’s lumican deficient it has a disorganized cornea, the cornea is cloudy, you inject these stem cells into the cornea, the cornea will reorganize into its proper structure and the clarity will be restored. And these are human stromal corneal stem cells and they take up residence and they stay there and so that’s what you see here. So these are the human corneal stromal stem cells sitting there. In a in a translational effort Funderburgh’s lab has paired with a group in Hyderabad, India that LV Prasad Eye Institute and ______ from the LV Prasad spent a year in Jim’s lab and has taken the technology back to India where they will attempt to use this technology in patients. And so we should know in the near future the efficacy of this technique in patients, but it would be very exciting to be able to take a cornea like that in a patient and with the application of these stem cells be able to restore corneal clarity. Another area of stem cell work in the cornea is work by D.P. Dhaliwal and Kira Lathrop. So Kira working with Larry Kageamann from our group was able to image the corneal the palisades and identify the areas where corneal epithelial stem cells reside. And so I think everybody in the audience knows the effect of the stem cell deficiency and this is the imaging of the corneal palisades Regenerative Medicine In Ophthalmology At The Fox Center For Vision Restoration, JOE S. SCHUMAN, MD 2 here. So this is human clinical in vivo OCT and processing the OCT you’re able to see the substructures. And just the way that Larry Kagemann showed the 3 dimensional reconstruction of the aqueous outflow system you can similarly do a reconstruction of the palisades. Finally in the cornea for the endothelium we created a program called the OTERO Program at Louis J. Fox Center for vision restoration and so the Fox Center is a part of the department of ophthalmology and it’s a collaborative effort between ophthalmology and the McGowan Institute. The McGowan Institute for regenerative medicine is one of the highlights of the University of Pittsburgh. It’s a fantastic organization if you don’t know about it I would encourage you to look on their website but we were able to pair with them to create the Fox Center and what the Fox Center does is to provide an infrastructure for clinicians and scientists of varying backgrounds to work together. And the OTERO Fellowship is specifically designed to take people who are in disparate fields let’s say a bioengineer and a clinician or a bioengineer and a basic scientist who’s a molecular biologist or cell biologist and pair them together to train a post doctoral fellow and that post doctoral fellow then learns the regenerative techniques that are being done outside the eye and can apply them to problems in the eye so that when their fellowship is completed they’ll be working on ocular regeneration. And so this is one of those projects and this is a project that’s a collaboration between Adam Feinberg who’s an engineer at Carnegie Mellon and Jim Funderburgh and Rochelle Palchesko is the OTERO fellow and OTERO provides $70,000 for a year of post doctoral fellowship training plus supplies and what they’ve found is that by changing the firmness of the substrate on which the cells grow they can stimulate the growth of corneal endothelial stem cells. So they’re not supposed to divide right and yet they have been able to get the cells to proliferate by changing the firmness of Regenerative Medicine In Ophthalmology At The Fox Center For Vision Restoration, JOE S. SCHUMAN, MD 3 that substrate. So that’s very exciting and we’re looking forward to the work that will be done but there’s a lot more work to do. I won’t spend really any time on this because you are going to hear from Dr. Du about her work but I’ll just say that Dr. Du was able to identify stem cells – was able to identify stem cells in the trabecular meshwork and was able to prove that those stem cells when injected into the eye will home to the trabecular meshwork and specifically if you’ve injured the trabecular meshwork that it will home to those areas of injury. Now the next step is will it repair those ares of injury and we’ll hear something about that but the first two things there are stem cells and they’ll home back to the trabecular meshwork I think is quite exciting and I’m – I’m really excited to be having the opportunity to collaborate with Dr. Du. You’ve heard a number of presentations from our Glaucoma Imaging Group, this is a sort of an old photo but it gives you a sense of the group and of our basically faculty and students. And you hard from Larry Kagemann who talked to you about imaging the aqueous outflow system and this should turn just like it did for Larry. And so Larry has been able to image the aqueous outflow system and this is a 3-D reconstruction, a part of which Larry showed you before but it gives you a sense of the outflow system in a actually human cadaver eye, and so this is what the outflow system looks like in that eye. And since that time Larry has gone on to create reconstructions in living human eyes but not 360 degrees. And the reason is that it is very time intensive, and it’s not easy. Regenerative Medicine In Ophthalmology At The Fox Center For Vision Restoration, JOE S. SCHUMAN, MD 4 We have two scientists who are working on retinal regeneration, so you may ask yourself well if a newt can regenerate its – you know its arm or leg or if it can regenerate its eye or retina why can’t we? The machinery must be there, why can’t we do that? And so if you look you know you have these stem cells that will proliferate ad infinitum in a newt or a salamander, in a fish you can regenerate the retina, in a chicken you do have stem cells, how about in vertebrates? Well in mammals you may or may not be able to regenerate the retina and there are stem cells that are in he retina in normal humans and this is work from Hongjun Liu who just joined our department and Hongjun Liu has identified a subset of amacrine cells that are what’s called Lgr 5 positive. And these, that’s a marker for stemness, so these are stem cells in the human retina. Actually this is in rats. And this is showing you the Lgr 5 positive cells and where they are located. These are all nuclei, here you see the Lgr 5 positive cells. And they are not ciliary body cells, there was this hypothesis a number of years ago that there were stem cells in the retina at the area of the ciliary body in humans but we do know that that exists in lower animals, not in vertebrate mammals. And then here is evidence that these are in fact amacrine cells. So what Hongiun Liu has shown so far is that the stem cells exist in adult mice, that they are amacrine cells and they possess all the properties of differentiated neurons and yet they can proliferate and generate other retinal cell types that in fact they are stem cells both in vitro and in vivo and that the mammalian retina has plasticity and these cells can function as adult retinal stem cells. Regenerative Medicine In Ophthalmology At The Fox Center For Vision Restoration, JOE S. SCHUMAN, MD 5 Another scientist who is working on stem cells in the retina in our labs is Igor Nasonkin. Igor is the Assistant Director for the Fox Center, he is the Salvati Assistant Professor of Ophthalmology. I should mention that Jim Funderburgh is the Associate Director of the Fox Center and so as the Salvati Professor Igor is running the Retinal Regeneration Laboratories which are soon to be unveiled as the Snyder Retinal Regeneration Laboratories thanks to the generosity of the Snyders and he is basically running 3 projects. One is grafting stem cells to the mammalian retina for cell replacement, another is using epigenetics for retinal regeneration and finally doing retinal genomics for personalized therapies for vision loss and this is an example of grafting photoreceptors and here you see the stem cell graft to regenerate photoreceptors and you can see that there is the integration of some of these cells. And this is a very brief cartoon about methylation and how epigenetics works but basically you have the machinery but it may be on or off depending on whether or not the chromosome, that area of the DNA is methylated. So the methylation controls the access to that DNA for translation. And so there are these epigenetic mechanisms that play a role in plasticity of the cells in the retina and here is a brief description from Igor as far as how he plans to use this as an approach to regenerate retina. We do also have a scientist working on optic nerve regeneration, he came out of Jeff Goldberg’s lab and this scientist Mike Steketee is using a couple of different approaches to work on regeneration of the optic nerve. Up until I don’t know a year ago I probably would have said that it’s very unlikely that we would see optic nerve regeneration within the next 10 years. We had a meeting here this Regenerative Medicine In Ophthalmology At The Fox Center For Vision Restoration, JOE S. SCHUMAN, MD 6 June specifically on regenerative ophthalmology and Larry Benowitz and Jeff Goldberg were both here and presented really exciting data showing robust optic nerve regeneration, really just very, very fascinating and exciting. And so Mike is following up on some of the work that they talked about but a number of original projects that he’s working on including collaborative work with Steve Badylak looking at the role of extracellular matrix in promoting the growth of ganglion cell axons. This is work by Matt Smith, so Matt Smith is doing very basic science in a nonhuman primate model and what he is looking at is visual perception. So when the nonhuman primate is shown an object what neurons fire in order to understand – for that monkey to understand what it’s seeing. And so he’s doing single cell recordings 100 cells at a time using these Utah rays. And so you might say well you know what does that have to do with regenerative medicine? Well we have a kind of a crazy project going on and that crazy project involves the head of neurobiology and also the head of the neuro technology center and so that’s Peter Strick and Andrew Schwartz. And Dr. Schwartz is the person who is responsible for the quadriplegics being able to use their thoughts in order to control a mechanical hand. I don’t know if any of you saw that it was on, it was in the popular literature as well as the scientific literature and it was also I think on 60 minutes or 20/20 or one of those T.V. shows and it’s very exciting, it really is. I mean it’s the first time that you could basically use your thoughts to control an external object except for the people who can do telekinesis and that’s outside of the scope of this lecture. And so instead of recording single cells, if we can understand how the brain interprets visual information in order to make a visual construct we would be able to provide a true vision back to people who have lost it and so this visual neuroprosthesis Regenerative Medicine In Ophthalmology At The Fox Center For Vision Restoration, JOE S. SCHUMAN, MD 7 project is crazy, exciting, it will take a long time to do and a lot of money. But we’re very excited about it and if you don’t set out to do it you’ll never accomplish it. So this is a priority project for our group. Can you pause that for just a second. Okay, so the person you just heard and you’ll hear it for a few seconds is Amy Nau. Amy Nau is our head of optometry, she’s an optometrist, clinician, scientist and she is working with sensory substitution so there’s a company very close to Paul Kelfman which is called Wicab. Wicab was started by Paul Bach-y-Rita and Bach-y-Rita had this idea that you could use a part of the body other than the intended sensory portion of the body to provide sensory information and in this case we’re taking people who are blind and by blind I mean light perception or no light perception and giving them visual information on their tongue. And so there’s a video camera that feeds to a computer that feeds to a tongue stimulator and it’s completely you know noninvasive and fairly simple to use. It doesn’t provide true vision to the patients but it does provide enough visual information to them so that they can experience the visual world independently. So now can you put the video on. VIDEO PLAYS So in this brief presentation I don’t have enough time to share with you all the data that Amy has gathered but she’s done a fair amount of scientific study to show the efficacy of this device but also to show where the information is processed and this will kind of blow your mind. As it turns out in Regenerative Medicine In Ophthalmology At The Fox Center For Vision Restoration, JOE S. SCHUMAN, MD 8 people who are blind the information from this device once they’re trained which is about a week or two of training and use, is processed not in the tactile portion of the brain but in the visual cortex. And if you take a group of healthy people who are normally sighted that doesn’t happen and it’s really a fascinating aspect of neuroplasticity in the visual system which we all were taught we’re hardwired, but in fact you know part of the brain can be used that’s not being used and the brain’s even smarter than we thought it was maybe. Let me show you 2 other short videos. So here’s one, can you start this one please? VIDEO PLAYS So that’s somebody who’s LP or NLP and was able to do that. Then the last video that I’m going to show you is Eric Weihenmayer who’s a blind climber I think he was the first blind person to climb Mt. Everest and it’s a vide from the NIH. And he’s the person on the bottom right. The PET CTs are what you’re seeing up on the top right. Amy has now done studies with Kevin Chan the person who’s working with Ian showing similar findings with FMRI. And this is where she sees things going now instead of having a tongue stimulator we foresee the stimulator being applied to the hard palate and you can put your tongue up against it at any point and then it would be wirelessly transmitting the information. Obviously having something that you take in and out of your mouth interferes with your daily activities, this would be a little bit less intrusive. Okay can you start this video please? Regenerative Medicine In Ophthalmology At The Fox Center For Vision Restoration, JOE S. SCHUMAN, MD 9 VIDEO PLAYS Thank you very much.