Vets First Podcast

In this episode of the Vets First Podcast, hosts Dr. Levi Sowers and Brandon Rea interview Dr. Steven Fliesler, a SUNY Distinguished Professor at the University of Buffalo and a career scientist at the VA in Buffalo, New York. Dr. Fliesler holds positions as an endowed Chair of Ophthalmology and Director of Research in the Department of Ophthalmology.

Dr. Fliesler was born and raised in New York and moved to California at the age of 15. He attended the College of San Mateo, the University of California in San Diego, and the University of California Berkeley during his undergraduate education and later obtained his PhD in Biochemistry at Rice University. During his time at Rice, his professor in neurobiology needed someone, particularly a chemist, to give a lecture about the chemistry of vision. This led Dr. Fliesler to an opportunity at the Baylor College of Medicine, where he did a postdoctoral fellowship in the Department of Ophthalmology. From there, he has distinguished himself in research and teaching within the vision field and has since been interested in research towards helping Veterans with mild traumatic brain injury (TBI). 

Throughout this episode, Dr. Fliesler discusses how he started researching TBI and why it interests him. First, he talks about what inspired him to enter blast injury research and highlights his collaboration with one of his colleagues. He then talks about utilizing animal models to better understand visual abnormalities found in trauma patients at the VA and converses about the methodology he used to quantify the visual effects of TBI, both behaviorally and physiologically. 

Later, Dr. Fliesler further describes his exploration into blast research with a professor at the University of Buffalo. He comments on the effects of auditory blasts that cause trauma in mice and how that affects visual function. Then, he discusses the various mechanisms that causes visual deficits and how it is important to understand in the context of TBI in order to rescue visual impairments. Finally, he hypothesizes on how the human body reacts to TBI. 

If you are a Veteran or you know a Veteran needing help with visual loss, contact the Visual Impairment Services Team coordinator at your nearest VA medical center or contact the Blind Rehabilitation Service Program by phone which can be found here. There are 13 Blind Rehabilitation Centers around the country, which can help with things like mobility, communication, and living with vision loss. 

What is Vets First Podcast?

The Vets First podcast is a research-based podcast that focuses on the VA healthcare system and its patients. Instead of being just another research podcast, the Vets First podcast was created with a primary focus on the Veterans and their stories. The hosts, Levi Sowers PhD, and Brandon Rea work to bridge the gap between the state-of-the-art research being performed at Veterans Affairs and the Veterans themselves in an easy-to-understand manner. Importantly, Levi and Brandon want to assist researchers around the country to better understand the needs of Veterans. In this podcast you will hear interviews from Veterans with specific conditions and then hear from VA funded researchers who are studying those very topics as well as other highlighted services the VA provides.

The Department of Veterans Affairs does not endorse or officially sanction any entities that may be discussed in this podcast, nor any media, products or services they may provide.

Announcer: Welcome to the Vets First Podcast, a research-based conversation centered around the VA health care system, its services, and patients. From Iowa city, Iowa, here's your hosts: Dr. Levi Sowers and Brandon Rea.

Brandon Rea: Hello, everyone. Welcome back to the Vets First podcast with us today, we have Dr. Steve Fliesler.

Levi Sowers: He's a Sydney distinguished professor at the University of Buffalo and a research career scientist at the VA in Buffalo, New York. He's also an endowed chair of ophthalmology and a vice chair director of research in the Department of Ophthalmology. So welcome to the Vets First podcast. Steve. Really appreciate you coming here.

Steve Fliesler: Great to be here. Thanks for the very kind invitation.

Levi Sowers: Yeah. So Steve, you have the longest CV I've ever seen. It's quite impressive. You know, one thing we really like to start with here is, where did you come from and how did you get interested in your research? You know, where did you grow up at?

Steve Fliesler: So I was born in Albany, New York, and my parents moved us down state to Yonkers and then to East Chester, New York. And I went to elementary school and early stages of my educational experience until I was 15. And then my dad got a really good job opportunity out in the San Francisco Bay area. So we moved when I was in the 10th grade to San Mateo, California, and I went to high school there and then I stayed in California. I went to a junior college for two years, the College of San Mateo and then I transferred down to the University of California in San Diego, where I was a chemistry major. And I did my junior year there. And then I got interested more in biochemistry. And one of the preeminent departments of biochemistry in the entire world is at UC Berkeley. So I transferred up my senior year to Berkeley to finish my Bachelor's of Arts there, and then I got an offer to go to Rice University in Houston, Texas, in the Department of Biochemistry at that time. This was in the early seventies. They had just started a biochemistry department there, and they were offering full graduate scholarships, including a living stipend. And this was during a time during the Vietnam War era where there were a lot of graduate programs closing down a lot of the graduate support mechanisms through the federal government were dwindling. And so I needed a place where I was going to be able to afford to live someplace and go to graduate school at the same time.

Levi Sowers: Yeah, very nice.

Steve Fliesler: So I got a full ride and I got a Ph.D. in biochemistry at Rice University, which is a very fine private institution. And during the time I was in graduate school, I was taking a graduate level neurobiology course. And the the professor at the time was going over all of the sensory modalities, vision and hearing, touch and smell. And he said, “You know, you're a chemist, we need to have somebody give us a lecture on the chemistry of vision.” And I said, “I don't know anything about that.” He said, “Oh, good, you have two weeks to learn.”

[laughter]

Levi Sowers: That’s kind of amazing.

Brandon Rea: No pressure!

Steve Fliesler: So I just read everything I could and I gave this lecture which actually came out pretty well. And it turned out in the course of studying, I found out that just basically across the street at the Texas Medical Center at Baylor College of Medicine, there was one of the top three or four departments of ophthalmology with a world class vision research group. And so I started going over there talking to the faculty over there, and they said, “Hey, you know, when you finish your PhD, why don't you come over and do a postdoctoral fellowship here?” I said, “Great. You know, I don't have anything else lined up.” And so I got a fellowship and I went over to Baylor. That was a really good move.

Levi Sowers: And how old were you at the time?

Steve Fliesler: So at the time I would have been about 26.

Levi Sowers: Yeah.

Steve Fliesler: 27 maybe.

Levi Sowers: Alright, yeah.

Steve Fliesler: And so I did a postdoctoral fellowship there for three years and they said, “Why don't you write your own grant application If you get funded, we'll give you a research instructor faculty level.” Well, I got funded on the first shot - which was one of the only times that ever happened in my life. But I got a NIH grant as an independent investigator and I became a research instructor at Baylor at what was called the Cullen Eye Institute, which is still there today. And then, while I was working there, I was working with two really outstanding vision scientists, and they were my mentors for the early phase of my career. And then an opportunity came at Bascom Palmer Eye Institute at the University of Florida, which is the number one ophthalmology department in the United States. And it still is. And it has been for, I don't know, three decades. So I got an offer to join the faculty as a tenure track assistant professor and a really nice startup package. And I moved to Miami and it was fantastic. But it was during that time, this was in the early mid-eighties that there was a lot of drug related crime going on in Miami. There was a television show at the time called Miami Vice.

[laughter]

Steve Fliesler: My relatives would call and say, “So is that what it's like living in Miami?” “Well, depending on where you are, yes.” So anyway, it became a kind of a tenuous place to live. And I was at a meeting over in Spain, actually in 1984, and I met up with a couple of guys from the University of Southern California at this conference. And I was giving a research talk there. And after my talk, they said, “Hey, you want to go get some drinks and have some dinner?” I said, “Great!” So during dinner they said, “How would you like to move to Saint Louis? There's an institute there, and we're just starting up a vigorous research program there.” And this is one of the guys from the University of Southern California who was moving there as the director of research. And I said, “Well, I don't know. It's kind of far away from the water.”

[laughter]

Steve Fliesler: And he said, “Yeah, just come up and just take a look at the job, okay?” So I said, “All right, I got nothing to lose.” So I flew up there. I spent the weekend, had a really good time. I really liked the town I came back to. I told my wife that I got this job offer to go to Saint Louis, and she said, “Where, exactly, is that that? How far inland is that?”

Brandon Rea: We get that response a lot, being in Iowa.

Levi Sowers: Oh, yeah, for sure.

Steve Fliesler: So I ended up taking that job offer now and only been an assistant professor at the time for three years. And as you guys know, it usually takes a good six years to get up the ladder to the next rung as an associate professor and tenured. Well, part of the move was I was promoted to an associate professor after three years and two years later because there was a residency requirement at Saint Louis University. I was tenured and then just a few years later I became a full professor in 1994. And I have been on, you know, that rung for the rest of my life. So I spent 20 years in Saint Louis and I was doing vision research and carrying out grant funded research. In fact, my research program has been continuously funded ever since I was an assistant professor.

Levi Sowers: That's pretty impressive. So how did you when did you make the move to Buffalo and how did you become involved with veterans research?

Steve Fliesler: So that's another - so everything that I've told you has been serendipity, right? So I never looked for a job, I never looked for a position. People just came out of the woodwork and said, “Why don't you join us?” I said, “Fine, okay.” So the same thing happened. I was at a big eye research meeting, the ARVO meeting. You guys may know about this, and I was talking to a friend of mine who happens to be on the faculty here at University of Buffalo, and I was talking to him at his poster and he said, “You know, we just got money for an endowed chair professorship. Would you be interested in interviewing for that?” I said, “No, I'm pretty happy in St Louis and I'm already a full professor. You know, I have a really good lab. Everything's good.” He said, “So why don't you just take a look, okay?” Just kind of like the St Louis thing.

[laughter]

Levi Sowers: Seems to be a theme with you. Yes.

Steve Fliesler: So I said, “Well, I've got nothing to lose, Right?” So I told my wife I was going for an interview. She said, “Buffalo, where's that?”

[laughter]

Brandon Rea: It's the one spot on the Continental US you haven't been yet.

Steve Fliesler: She said, “How close is that to New York City?” I said, “Not very. About a seven hour drive, clear on the other side of the state.” So I came in interview. I had a really good experience and on the spot, they offered me the job and they hadn't even interviewed anybody else. And I said to the department chair, “Don't you at least want to interview somebody else?” He goes, “No, you're exactly what I'm looking for.” I said, “Listen, before I married my wife, I actually dated several women. And then I decided on her and I married her. By the way, the car that I'm driving, I test drove a whole bunch of cars before I bought that car. Really? Don't you want to look at somebody else that.” “No, I don't.” And he said - you know, he was driving me to the airport to go home- and he said, “What's it going to take to get you here?” I said, “Well, the first thing it's going to take is for my wife to agree to move to Buffalo, New York.” So we had a good conversation that worked out. I got a very good starter package. I came here in 2008 and I've been here ever since. So it's 14 years this summer. Then, the VA thing was also very serendipitous because several of the researchers in the ophthalmology department have laboratories at the V.A. So I came over and I looked at the VA and I said, you know, this would be great if we could all be, you know, together. And, you know, right down the hall from each other. And we're not even paying rent here. It's a pretty sweet deal at the VA. Also, the associate chief of staff said, “You know, you would be eligible to get a merit grant and you could get a salary line on top of your university line.” And I went, oh, that's a unbelievable sweet. So I said, “What do I have to do?” So he told me and I applied and I got my merit grant after the second try. So…that's how I came here. And it’s worked out really nicely. But how did I get into blast research? I wasn't doing anything like that in my prior career. So, you know, they made it very clear if you're going to work at the V.A., you have to do something that's relevant to the VA population. Okay? So I was looking at the literature and I said, you know, we just don't really know a lot about what happens after a primary blast explosion that goes off that soldiers get knocked over and unconscious and when they come to their ears are ringing, they get a really bad headache. They got a concussion. And if they are fortunate enough to not have a penetrating injury and they have a you know, their eyes are intact, it's called primary blast exposure.

Levi Sowers: Yeah.

Steve Fliesler: They don't exhibit any overt immediate symptoms. And what the really weird thing is. Weeks, maybe months later, they start complaining of double vision, of other kinds of acuity problems, even color hue discrimination, contrast sensitivity differences. And when they go to their VA hospital, after the discharge, the docs look at the field notes and they’ll just say, “Well, it says here, you know, you can count fingers and you didn't have any overt signs, you didn't have hemorrhaging and you have a retinal tear that everything looks good and you didn't have a cataract. We think your visual problem is in your brain.” Okay? Because obviously you got a really bad concussion and that could be. But I had the suspicion that there was something going on in the front end of the system. The camera, basically. The eyes, right.

Levi Sowers: Mmhmm.

Steve Fliesler: So again, serendipity. I saw a seminar announced on traumatic brain injury and there was a guy in the Department of neurosurgery here, David Paulson, who was giving this talk. So I sat in on that talk and I was, you know, watching his stuff. And it was - he had a really good rodent model, a rat model for mild traumatic brain injury, TBI. And he said, you know, “These guys have a cognitive deficit.” I said, “How do you measure that?” “Oh, we use this thing called the water maze, and we train rats to swim to an exit. And the other part of the maze is blocked off and they have to learn where the exit is or they learn to swim to a platform that they can rest and not have to tread water.”

Levi Sowers: Yeah.

Steve Fliesler: I said, Well, you know, all of those tests are visually guided behavior. If you blindfolded those rats, they'd never learn that. Okay? So I said, “Have you ever looked at what happens to the rats that you induce a TBI in as far as their eyes?” And he said, “No, we don't even know how to do that.” I said, “You're in luck. I happen to know how to do that.” Okay? So I said, “Listen, next time you do some animals, give me a couple of the eyes from the animals after you sacrifice them and we'll fix them and we'll section them and we will look at their histology, their morphology of what the retina looks like, and also do some immunohistochemical stains that we can detect things that are upregulated in response to trauma. One of these molecules is called GFAP, glial fibrillary acidic protein. And normally in the retina, the expression of this protein is very, very low levels and only localized to the interface between the neural retina and the vitreous. But when you have a trauma or multi-generation that's going on in an animal or even in a human, what happens is this GFAP molecule gets dramatically upregulated and you see this huge labeling pattern in the neural retina. And it's a signature. It's the canary in the mineshaft that there's something wrong in the neuronal environment, even though this molecule is not synthesized in the neurons, in the retina, it's synthesized by the glial support cells, the Muller cells, for instance, as well as the astrocytes. So when I looked at a few eyes from animals that had a mild TBI and compared them to animals that were not traumatically injured, I saw a dramatic upregulation in GFAP in the retina. And I told this to Dr. Paulson. I said, “I'm telling you there's something going on. But,” I said, “how do you induce this TBI?” Well, he does it through a direct cortical impact called a lateral fluid percussion or LFP.

Levi Sowers: Okay.

Steve Fliesler: And this uses a fluid driven stainless steel piston that just impacts the open skull directly on the cortex, just one hemisphere, and that's it. You get one impact or maybe repetitive impacts. And then it's miraculous. You just glue the cranium back on and the animals survive. They probably have a headache, but they go about their lives and whatever. So, you know, he tests them and then at the end of the experiment and he's humanely euthanized as the animals, I got the eyes. And sure enough that these animals, when they receive a direct impact to their brain, not to their eyes, they show this massive upregulation of GFAP.

Levi Sowers: Yeah, that's really interesting. You know, I think one thing, if we take a step back just for one second, when you describe they're using rats to study TBI and rat eyes to study TBI, what's the importance of using animal models to study these sorts of injuries? You know, we've had questions from veterans, and I think legitimately so, why do we look at animals when we're dealing with humans?

Steve Fliesler: Yeah, so that's a very good question. So the kinds of things that we- the tools that we need to assess the molecular changes in the eye, you can't do with a human being, okay, because you have to - you're not going to live or live well- if we took your eyes out to do an experiment.

Levi Sowers: Yeah, of course.

Steve Fliesler: So we need to use a- an experimental animal that is easily obtainable that is able to be maintained in the laboratory environment and is reasonably priced as well. And also that has anatomical features that are similar enough to the human that they mimic the fundamental biology that is shared by all vertebrates. Okay. Now, some people do experiments with primates. Okay, well, primates are very expensive. There are a lot of restrictions on using primates and also they are generally not congenital, which means that they are not the same lineage with the same background genetics, just like you're different than Brandon, for instance. Okay. So the beauty of using rodent models is that you can get genetically identical animals and breed them over and over and they will maintain their genetics over generations. So you want to reduce the number of variables in any given experiment. So if you don't have any genetic variability in the background, you're already off to a good start.

Levi Sowers: Yeah!

Steve Fliesler: The thing is, it also has to be what we call tractable, in other words, usable convening, and that you can do certain kinds of tests that will be informative to you that are actually reasonably easy to do. Okay, so measuring their visual acuity, for instance, we can do that in a rat. You know, they don't have to be like a person where you say, “How is this lens? Does this look better or worse?” Okay, so you can't talk to a rat. But there are ways that we can objectively measure visual acuity. We can also measure the sensitivity and reactivity of the retina to stimulation by light and increasing flashes of brightness of lights and different colors of lights or frequencies. So these are all electrophysiological functional outcomes assessments. And we do those kinds of things. Those tests I do in collaboration with a wonderful VA collaborator at the Atlanta VA, Dr. Michelle Park. We- in my laboratory, our expertise is most well developed with biochemical and immunohistochemical and morphological techniques. So after we do visual assessments on the animals through a collaboration, the eyes are then sent back to us, and then we do biochemical and immunohistochemical and morphological assessment assessments of the retinas.

Brandon Rea: Yeah, that's what I always find fascinating about AI in model organisms of that- that have eyes like rats, mice, you know, any number is that the eye maintains this biology across so much of evolution it's very impressive. So what we learn, I think you can totally correct me if I'm wrong, but what we learn in the eye of a rat is very applicable to a human. Often there are some things that aren't, but the biology is so similar that it's really informative for human biology and human disease offsets.

Steve Fliesler: That's correct. So the fundamental cell biology of the retina that the wiring diagram, if you will, of the neurons and their connections fundamentally is the same as in a human. There are some things that are very distinct. For instance, rodents don't have a macula or a focal center that is a cone rich region in the center of the visual axis. Only humans and primates have macular and a phobia, so they have a somewhat different organization. However, if you just looking at rod cells, the rod cells in rodents are very similar to the rod cells in humans. The cones. There are three kinds of cones in humans and primates and the fundamental structure of cones and their visual pigment biochemistry and all of their signal transduction mechanisms are essentially the same. The fundamental biochemistry and cell biology of the cells of the retinas of a rat are pretty much like human. Okay? So we think that we can model certain things in rodent animals and they will be informative for what's going on in humans. Okay? So I'm telling you this story further about how did I ever get into the blast injury business. The first was that model TBI lecture. The second was, again, going to a research seminar by another colleague who happens to be an expert in the auditory system, and he is a world expert in what's called tinnitus, a very common auditory defect in humans. And pretty much anybody who gets exposed to a blast, a loud noise or in- even in direct impact to the side of the head that affects the auditory system. They will have this ringing in their ear. Okay. And they will have this tinnitus. Okay. So there's millions of people in the civilian population that are affected by tinnitus, but our deployed soldiers are very prone to having tinnitus and auditory defects. So I went to his seminar and he was studying blast injury to the auditory system and he was using a model blast generator which was actually built from parts that you can buy at Home Depot and a really talented engineer in the mechanical engineering department at the University of Buffalo designed and built this blast generator. And it basically fills up with a column of air to a given pressure. And there's a hunting arrow that is mounted inside a PVC pipe that is driven by a solenoid at will. If you activate it, it will drive the hunting arrow forward. And that what we'll do there will pierce a film, a metal film that is covering the mouth of the tube. And there's that back pressure of that building up behind that piece of metal film. When that arrow punctures that film, it's releases this blast of air and it releases a sound wave. And the sound wave can be incredibly loud. The one that we typically use is 190 to 195 decibel.

Levi Sowers: So it doesn't surprise me. We had an overpressure chamber that we worked with for years and it was super loud. Oh, man. You know, we have to wear hearing protection while we use it.

Steve Fliesler: So we- I have built a sound enclosure, a soundproof acoustic chamber. So this device is mounted on a table. The animals are deeply anesthetized. They have no pain sensation whatsoever and they are in this free standing room that's within a room. And we are outside monitoring this. And then the explosion goes off. The blast goes off and then we recover the animals and then we will then allow them to recover and they wake up and they're fine. And, you know, animals that are severely injured, they won't eat or drink. They won't move around the cage. You'll be lethargic. Our animals eat, drink, walk around. They probably have a headache. Initially. We give them, by the way, analgesics to reduce, to minimize those headaches. And we use topical anesthesia so that they don't have any surface effects of pain from the blast wave. But the eyes are intact. The animal is intact. And then days, two weeks, even months later, we do visual assessments on these animals and then we do biochemical and cell biologic assessments on animals. So going back to this seminar, this colleague, Dr. Richard Salvi at the University of Buffalo, he again was doing cognitive testing on these animals. And I asked him, “Did you assess the vision?” He said, “No, we take out the ears, inner ear workings and the brains.” Okay. “But we generally throw the rest of the animal away, including the eyes.” I said, “Well, next time you do this experiment, would you please give us some eyes and I'll take a look at them?”

[laughter]

Levi Sowers: Just give me those eyes!

Steve Fliesler: Sure enough, just like with the TBI experiment, we saw this GFAP molecule. Just huge. Humongous upregulate.

Brandon Rea: Upregulated.

Steve Fliesler: So then I said, “All right, listen, we have got to collaborate on this. But,” I said, “I have to do the experiments at the VA so I can't be using your device.” So I had the identical instrument built-”

Levi Sowers: And so you went to home Depot.

[laughter]

Steve Fliesler: Yeah. So that's- that really launched my career. He and I both wrote a VA merit grant on poly trauma, and that was the first grant that I got funded through the VA system. And I still have that grant today.

Levi Sowers:Wow. That’s awesome.

Brandon Rea: So where did you- that well, that's a lot and that's awesome. So where do you see your- where do you see your research going now?

Steve Fliesler: So, you know, the first part of the research was trying to just to figure out the fundamental mechanisms of how is the retina reacting to having a primary blast, because it doesn't do anything directly physically. There's nothing that you can see that happens to the eye. Okay. They looked perfectly normal after this blast exposure, but they're not normal. Okay. So because these animals start to have visual deficits and they also have these sequelae, these after effects that are measured at the molecular level, we said, you know, what we really need is to figure out a way to dampen those sequelae, to reduce the visual deficits that are caused by blast injury. So what would you do? Okay. Well, you would have to know what is causing the visual deficits to begin with. That's why we had to know what are the pathways that are affected. Okay. And what we came up with and other people have been studying this by the way, I'm not the only person in the world during this, but one of the mechanisms that seemed to be jumping out at us was oxidative stress and there are a lot of hereditary retinal degeneration as well as traumatic retinal generations that involve oxidative stress or the release of free radicals. So we thought, well, maybe we'll just give them antioxidants, just like, for instance, people who are in the early stages of their disease of age related macular degeneration. They take a mixture of antioxidants, water soluble and fat soluble antioxidants like vitamin C and vitamin E and vitamin K, These kinds of naturally occurring FDA approved antioxidants that happen to be vitamins. We take them every day in our multivitamins. Okay. But you need really megadoses of these to be effective enough to be protective or reduce the progression is what they do, at least in people having age related macular degeneration. So we said, well, why don't we just give these guys some vitamin C and some vitamin E and maybe some selenium, because selenium is a cofactor for some detoxifying enzymes, I could find Peroxidation. So we said, okay, let's just check that out. Well, that approach didn't really pan out. And, you know, it was very attractive because we wouldn't have to go through FDA approval. People are already taking this stuff anyway, right? Well, then I heard this guy give a talk and he was a medicinal chemist, Peter Cator at the University of Nebraska, and he was developing a whole series, a new family of very, very potent antioxidants that are what are called by functional reagents, which means they do two things. Okay? The two things that they do is one end of the molecule traps and sequesters free radicals or annihilates them. It's called the other end of the molecule Chelating iron and iron is responsible for non enzymatic, just pure chemistry driven generation of free radicals. Okay, so you tie up the iron and you quench any of the free radicals that are floating around and you get a twofer double whammy, very, very potent antioxidant. And these things are they have kind of a very unusual chemistry and they're not easy to make and they're not cheap to make. Unlike, you know, getting vitamin C, for instance. So we had to collaborate with him to do this. And these are proprietary compounds. So the idea was we would put these proprietary antioxidants into the diet of the rats that we're treating, and some of the animals will get the antioxidants and some of the animals won't. And then we'll expose the animals to blast injury and then ask, do we get a better visual outcomes or reduce the molecular signatures of damage in the animals treated with the antioxidants? And so the answer, the long and short of it is the original. The initial research that we did, it looked like it might work. But after doing a lot more animals, we don't have a compelling, statistically significant outcome that shows that the visual function is improved at all. What we do see is that we can get the dampening down of some of the signatures of oxidative stress and a molecular reactivity of the neurons, and yet in the retina. So we, we, we think that the idea still has merit, we think it needs to be refined and we are working on now another class of molecules that again is a pharmacological compound. This one is FDA approved, that is a inhibitor of one of the enzymes that generates free, free radicals in every cell in your body. And this class of molecules has some very promising clinical signs, as they might be the kind of molecule that we need to be looking at for our blast injury model. So that's where my research on blast injury is now heading. And we're very hopeful because, you know, before I retire, I would like to, when I go out the door, know that I did something that actually is going to improve veterans health.

Levi Sowers: Yeah.

Steve Fliesler: And I see some of these- especially these young guys that are coming in from the war in Afghanistan. And they are, you know, very damaged. And if there was if there was something that I could have the Department of Defense distributed to every deployed soldier or that they just put in their diet, just like, you know, just take a pill and eat breakfast and they go off to their field maneuvers and let's say they get an IED, go off, that the the damage that has occurred to them is somehow signified, equally reduced, and they don't lose their vision and they don't have the sequelae of exposure to a primary blast. The unfortunate people that, you know, have penetrating injuries. Those things you need surgical intervention. No, no pill is going to help those people. But the people who and there's a lot of them come out of a blast. They don't have, fortunately, no physical damage them. But they have the tinnitus, they have the concussive injury, they have the TBI, and they also have the visual dysfunction that takes a long time to manifest. Okay.

Levi Sowers: You know that that's been something that I've really thought about in my TBI work for a long time is why is there such a delay there? What's causing that delay and why would the body upregulate these sort of pathways that could injure itself? Because it's probably trying to protect itself from damage, right, like in some way. And we know that there's- like the neurons get sheared a little bit, especially the retinal ganglion cells are project way back in the brain and that these really long projections. So could it be that these cells are actually getting damaged in some way that we don't see?

Steve Fliesler: Yes. So the answer is yes. Likely there are microscopic changes that are going on that are not overt, that you can't see with the naked eye, for instance. If you have a torsional excision of the optic nerve, you can see that. But if there's just rotation of the eye and the twisting of the optic nerve, that will cause damage, but you will not see that that is a…a break in the cable, if you will.

Levi Sowers: Yeah.

Steve Fliesler: So- and in fact there's a researcher at San Antonio, Randy Glickman, Dr. Glickman, who has been studying an animal model where they purposely torque the optic nerve and look at the impact of that on the visual system because that kind of injury does occur in the field.

Levi Sowers: Yeah. Yeah. You know, It's just always been very perplexing to me that it takes such a long time for some of these things to manifest. And you know, one I think really interesting topic for the field I'm part of the vision center in Iowa and so I get to listen to all these vision talks all the time. And so one thing I've always wondered is like, what's the difference between someone who doesn't get any of these problems and someone who does genetically? Do you maybe you can't speak to this, I don't know. But like, do you know if there's any genetics background or predisposition that could lead to worse outcomes? Has the field even looked at that?

Steve Fliesler: The answer is I am unaware of it, and I don't know of any publications that have come out yet on this. Here's the thing. As a researcher, you know this. What's in your notebook, is in your notebook.

[laughter]

Brandon Rea: Yeah, that's so true. Yeah.

Steve Fliesler: You know, nobody else knows what you're doing. So I don't want to say nobody is studying that because I, I maybe wouldn't know that.

Brandon Rea: Yeah, I just don't know either.

Steve Fliesler: I haven't seen publications on and I don't think that people have done that kind of study. So there is a data resource called the Million Veterans Program-

Brandon Rea: Yeah.

Levi Sowers: Yup.

Steve Fliesler: and that is a data repository where that kind of a question could be post facto evaluated.

Levi Sowers: Yeah, absolutely. And that's going to be a major resource moving forward for the VA centered research community. I think it's really an impressive thing.

Steve Fliesler: So it's already yielding incredibly interesting insights into age related macular degeneration, susceptibility, glaucoma susceptibility, cataract formation, some of the other diseases of the eye, like Fuchs endothelial cell dystrophy, which is a corneal abnormality. These are all being studied currently and a data mining of the million veteran programs databank has been- is being done at Iowa, in fact. You have one of the world class neuro ophthalmology experts, Randy Cardin there, Marcus Cohen is studying glaucoma and ocular injury, trauma injury. Interestingly, I was on Marcus's Ph.D. thesis committee when he was a student at-

[laughter]

Brandon Rea: Really?

Levi Sowers: Oh, man that’s wild. Oh, wow. That’s so cool.

Steve Fliesler: And you probably know Rob Mullins, as well.

Brandon Rea:I don't personally know him, I know the name for sure.

Steve Fliesler: Rob studies age related macular degeneration and he and Marcus were both in the same laboratory at Greg Hagemann's laboratory at Saint Louis University. Greg had been- had moved to Iowa and now he's in Utah.

Levi Sowers: Oh, yeah, Marcus worked in Saint Louis for a long time.

Steve Fliesler: Yeah he was a, he was a graduate student and I was a Ph.D. on the Thesis committee.

Levi Sowers: So, Steve, this is the part of the we're almost done. And just like five more minutes. I just want to ask you a couple of, I think, fun/introspective questions for researchers. Did you ever picture yourself having a 74 page CV?

Steve Fliesler: You know, like, are there- was there was a time that I think my parents predicted I'd be in reform school. So I'm amazed I have a CV at all. Yeah. And I- you know, the listeners, you know, I was not born brilliant. Okay. I had a twin brother who actually was born brilliant. And he was always, you know, they would call him the smart one. Okay. But, you know, no, I never thought that I would make it this far in academia. I feel unbelievably lucky. I think, I tell people I was never the smartest knife in the drawer. Okay. But I've been in the right place at the right time, and I've had opportunities that have appeared out of nowhere. And I've just the one thing is I do recognize and have the ability to put together seemingly unrelated facts and make a story and come up with a hypothesis and pursue that. Okay. Yeah. So I have, you know, the fundamental basis. But for the listeners, I'm no genius. Okay.

Levi Sowers: Yeah, I'm not either, Steve. I think we are both in that same drawer there, you know? And then the other thing I really like to ask people is what do you do outside of science? What do you like to do for fun?

Steve Fliesler: Oh yeah. Okay. Several things. So living in Buffalo, we actually have a lot of outdoor kind of things to available to you.

Levi Sowers: I mean, if you live in Buffalo, you enjoy scooping snow during the winter.

Steve Fliesler: I've actually love taking my dog on walks on what you might consider tundra and which I just did a couple of weeks ago. And then the snow melted and we get more on Sunday. The other thing that I really am enthusiastic about, I've always had an interest in wine and this started actually in graduate school where some of my friends said, “Hey, why don't we form this like a wine club? And we'll sample different wines and we'll, you know, study them and learn about them.” And I said, “This is great,” you know and so I learned more and more and more, and I started collecting some wine. And so I have a pretty nice cellar and I have a couple of friends here that I hang out with, usually about once a month and we try some really good wines. And so I'm enthusiastic about that and I am what you might consider a gourmet chef.

Levi Sowers: Oh!

Brandon Rea: Nice.

Levi Sowers: I love cooking, too.

Steve Fliesler: I love cooking. It's my relaxation. I actually cook all of our dinners at home. I hate cleaning up, but my wife doesn't mind it. So I cook, she cleans. It's a- it's a good life. Hey, this was a blast. Thank you so much for inviting me to do this.

Levi Sowers: Thank you so much for doing it.

Steve Fliesler: I'm really looking forward to hearing the podcast when it comes out. You guys are doing a great thing. Thank you.

Levi Sowers: Thanks man, appreciate it.

Brandon Rea: Awesome. Thanks, dude!

Announcer: This concludes today's Vets First Podcast. For questions or comments relating to the program, please direct email correspondence to vetsfirstpodcast@gmail.com. Thanks for listening!