Pancreas transplants; COVID and pain; clues to a retinal disease: Upstate Medical University's HealthLink on Air for Sunday, Aug. 20, 2023

Host Amber Smith: Coming up next on Upstate's "HealthLink on Air," a transplant surgeon explains the benefits of a pancreas transplant.

Reza Saidi, MD: ... These patients actually live longer compared to the patients that are on insulin therapy, because insulin therapy is like a maintenance therapy. It doesn't cure the diabetes, but this pancreas transplant can cure diabetes..."

Host Amber Smith: A public health researcher discusses the connection between COVID-19 and chronic pain.

Jamie Romeiser, PhD: ... This could be musculoskeletal pain, it could be pain in your joints or in your muscles or even neurological pain. ..."

Host Amber Smith: And an ophthalmology and visual scientist shares the work he's done on progressive rod-cone degeneration.

Will Spencer, PhD: ... It's actually the most common cause of blindness in dogs. Well over 40 different dog breeds are affected by this disease. ...

Host Amber Smith: All that, and a visit from The Healing Muse, coming up after the news.

This is Upstate Medical University's "HealthLink on Air," your chance to explore health, science and medicine with the experts from Central New York's only academic medical center. I'm your host, Amber Smith.

On this week's show, we'll explore the connection between COVID-19 and chronic pain. Then we'll learn about a disease that causes blindness in dogs and humans. But first, who might benefit from a pancreas transplant?

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

More than 63,000 pancreas transplant surgeries have been performed worldwide. Just 8% of those were pancreas only. The rest were combined kidney and pancreas transplants.

Upstate's transplant surgery chief, Dr. Reza Saidi, explores the outcomes of pancreas transplants in a paper published in the World Journal of Surgery, and he's here to talk about it.

Welcome back to "HealthLink on Air," Dr. Saidi.

Reza Saidi, MD: Thanks, Amber. Glad to be here.

Host Amber Smith: Now, your paper looked at pancreas-only transplants between 2001 and 2020. What did you find?

Reza Saidi, MD: I think this is an interesting topic because the first pancreas transplant was done in the United States in 1964, and they did it for a wide variety of indications. As you pointed out, the majority of them are done for the patients who already have kidney disease and have diabetes, and they receive combined kidney, or pancreas after kidney, transplantation.

But a minority of patients with diabetes, with a very difficult time to manage their diabetes, or they get a lot of hypoglycemia, that means their blood sugar goes way down and can actually cause serious damage to patients, sometimes cause seizures, arrest or coma, and sometimes can be fatal.

And for those patients, a minority of patients, I think pancreas transplant can be an option. In the past, I think there were some papers that showed these patients actually don't do very well because pancreas transplant is a big operation.

But in this paper we look at outcomes of patients who receive pancreas transplant alone. This is only patients who have diabetes, that only for that indication have pancreas transplant. We've shown in the past 10 years actually, despite the fact that the number of these cases have gone down in the U.S. compared to the previous decade, the outcome has significantly improved. And these patients now, it seems that they do much, much better. And we passed the learning curve; we know how to do it. Even a selective group of patients, even with Type 2 diabetes, we can perform this operation. In the past, this was only just for the patient with Type 1 diabetes, but now with the experience that we gained doing pancreas transplant with the patient with Type 2 diabetes, it seems that this patient also might be a candidate.

But again, remember this is very selective for patients that the modern managing of diabetes failed, and they might be a candidate for pancreas transplantation.

Host Amber Smith: So the majority of the patients who receive a pancreas transplant are diabetics?

Reza Saidi, MD: Yes. I would say all of them are diabetic, but most of them have kidney disease, and on top of that they have diabetes, and they receive combined kidney and pancreas transplant.

But a minority of patients who just have diabetes, and it's very difficult to manage their diabetes, or they get a lot of hypoglycemia, might be a candidate for pancreas transplant alone, and our paper showed that their outcome has improved. And this is a valuable option for a minority of patients with diabetes that have a difficult time to manage their diabetes.

Host Amber Smith: So what are the survival rates like?

Reza Saidi, MD: In the past was in the 40% and 50% (range), but now it's close to 70%, which is very comparable to the patients who receive combined kidney/pancreas transplant or just receive a kidney transplant. And again, these are the patients who have difficulty to manage their diabetes.

And I think the survival of 70%, that's a pancreas allograft survival (the transplanted pancreas itself). The patient survival is very close to 100%.

Host Amber Smith: Now, the United Network for Organ Sharing reports that in addition to 97 kidney transplants in 2022 at Upstate, surgeons performed 22 kidney and pancreas transplants, and four pancreas-only transplants.

Does that sound right?

Reza Saidi, MD: That's correct.

Host Amber Smith: Can you go over again why someone would need both a kidney and a pancreas versus why someone would need only a pancreas?

Reza Saidi, MD: Patients who have kidney disease, chronic kidney disease, and have diabetes, they have shown that the best option for them is to have a combined kidney and pancreas transplant because, No. 1, with the combined kidney and pancreas transplant, you cure the kidney disease, and then you cure their diabetes, and because you cure their diabetes, they actually live longer, and they have much better quality of life.

But some people, as I said, a minority of people don't have kidney disease, but they have a very difficult time to manage their diabetes. Then these patients might be a candidate for just pancreas transplant alone. And data that we presented, that paper, clearly showed that afterward, those patients significantly improved in the past 10 years.

And this is a valuable option again for a minority of patients who have a difficult time to manage their diabetes.

Host Amber Smith: So for a patient who only has diabetes, and their kidneys are healthy, there would be no need to also do a kidney transplant.

Reza Saidi, MD: No. Pancreas transplant alone is only for the patients who just have diabetes, no kidney disease, but again, for a wide variety of reasons, they cannot manage their diabetes effectively, or they're getting a lot of hypoglycemia.

Host Amber Smith: So why aren't more people with Type 2 diabetes candidates for pancreas transplants?

Reza Saidi, MD: I think that's a very good point. So, as I said, in the past, people thought that this is a morbid operation with a lot of complications, and it is not worth it to do with this.

But now we learn from our experience, and we are getting better and better with our surgical technique, immunosuppression management, and also postoperative care, with ICU (intensive care unit) care. It seems that more and more this patient might be a candidate, and we learn in a selected group of patients.

Again, selection is a key in this area. You have to be very diligent who's a candidate for this operation. We can offer this operation for patients with Type 1 or maybe Type 2 diabetes.

And then let's point it out: The majority of patients with Type 2 diabetes are obese and old. They're not really candidates. For the patient who are relatively younger and not very obese, I think this might be a valuable option if they fail other, alternative treatment, such as insulin therapy.

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith. I'm talking with Dr. Reza Saidi. He's the chief of transplant surgery at Upstate, and we're talking about pancreas transplants.

Are there a growing number of transplant centers that are offering pancreas-only transplants to people with diabetes?

Reza Saidi, MD: Actually, unfortunately not. Because this is highly complex surgery, and because in the past, the outcome was not good, the majority of programs actually try to stay away from it.

A very few programs actually offer these options for the patient. For example, in, I would say, Upstate New York, we are the main program in offering these. Other programs actually not offering this treatment. But I think for a minority of patients, with the highly selective group of patients, that might be a viable option.

For example, recently we had a patient that we transplanted just the pancreas alone. This patient actually has a lot of hypoglycemia and has a couple of car accidents, and his driving license was revoked and has a poor quality of life, cannot get a job. And with this operation, he's back to a normal life of a good quality, and basically he's very happy.

Host Amber Smith: And when you talk about being selective in the patients, you're trying to choose a patient who the operation is going to be able to help.

Reza Saidi, MD: Absolutely, yes.

Host Amber Smith: So there are some things that might disqualify them. You mentioned obesity, right?

Reza Saidi, MD: Yeah. Morbid obesity, or if they have significant heart disease or have significant peripheral vascular (blood vessel) disease.

These are all a contraindication to proceed with a pancreas transplant.

As I said, selection is a key in this business, and you have to make sure you select the right patients for this operation.

Host Amber Smith: I wanted to ask you to walk us through how a pancreas-only transplant is done. Is this an organ transplant, or do you just transplant islets (pancreas cells involved with insulin production) from the donor pancreas?

Reza Saidi, MD: I'm talking about the whole-pancreas transplant. Islet transplant has also been done in the past, but unfortunately is still considered experimental because the long-term result is not comparable to whole-pancreas transplant. When I'm talking about pancreas transplant, I'm talking about the surgical procedure to transplant the whole pancreas in the patient.

Host Amber Smith: So in that respect, is it like a kidney transplant? You're taking an organ from a donor and putting it into the recipient?

Reza Saidi, MD: Yes, it's pretty much very similar to the kidney transplant. And I think the way we do it at Upstate, we do it very similar to a kidney transplant, and we do not touch the patient's own pancreas. That's going to stay in place.

Host Amber Smith: So the old pancreas remains?

Reza Saidi, MD: Yes.

The pancreas does a wide variety of functions. Some of the function has to do with food digestion. And the reason we do pancreas transplant is just because this pancreas can produce insulin, and the patient's own pancreas cannot do that.

Host Amber Smith: How soon after the operation does the new pancreas begin functioning?

Reza Saidi, MD: I would say almost immediately, because again, we select the best donors for this operation. The majority of these donors are young, who unfortunately might have died in a motor vehicle crash. And they're healthy.

That's why I would say close to 100% of these pancreases work right away.

Host Amber Smith: And what is recovery like after the surgery, for the recipient?

Reza Saidi, MD: The recovery is pretty much like a kidney transplant. The majority of these patients stay in the hospital maybe between five to seven days. And usually the full recovery takes about four to six weeks. And after that, the patient actually is back to normal, and again, won't require any insulin treatment. And because of that, these patients actually live longer compared to the patients that are on insulin treatment, insulin therapy, because insulin therapy is like a maintenance therapy. It doesn't cure the diabetes, but this pancreas transplant can cure diabetes.

Host Amber Smith: And so having a new pancreas, in terms of diabetes, if it cures the diabetes, does it also improve a person's overall health?

Reza Saidi, MD: Yes, absolutely. Actually, people have studied this because there are a lot of secondary complications of diabetes, like heart disease, peripheral vascular disease, eye disease, damage to the nerves, and people show that over time all those damages can be reversed.

That's why these patients actually live longer, because you cure the diabetes, and they can cause regression of secondary complications of diabetes.

Host Amber Smith: Now, I'm curious about what life is like for someone who has a pancreas transplant, because I've always heard that transplant recipients are taking immunosuppressant medicines for the rest of their life (to prevent their body's rejection of the transplanted organ).

Is that still true?

Reza Saidi, MD: That's correct. But now we have new medication with less side effects, safer, I think that that's why the majority of our patients, I feel more than 80% of these patients, go back to normal life and have no problem. But some of these patients, because of immunosuppression, can have some side effects, like develop a neuropathy (nerve damage) or develop, for example, cardiovascular disease or cancer.

But the majority of these patients actually do fine and tolerate the immunosuppression in the long term perfectly OK.

Host Amber Smith: Does having a pancreas transplant disqualify someone if they need a kidney transplant in the future?

Reza Saidi, MD: No, it doesn't.

Host Amber Smith: Now, if someone is listening who's got diabetes, and they're curious about whether they might be a candidate for a pancreas transplant, is this something that you find generally primary care providers are aware of?

Reza Saidi, MD: Primary care and endocrinologists, they should be aware of this. And that's why we try to get this message to the public and also to the primary care physician and endocrinologist. for a select group of patients, that might be the option. If they have the patients who have a difficult time to manage diabetes, or they get a lot of hypoglycemia, I think that pancreas transplant alone is a viable option for those patients. And at Upstate we're happy to see the patients and evaluate them and see if they're a candidate for pancreas transplant alone.

Host Amber Smith: What is the waiting list like for pancreas transplants?

Reza Saidi, MD: Actually, it's not very long. It's a small list because, as I said, for pancreas transplant alone it's a very selective group of patients. In the U.S., roughly 150 or 200 of these cases are done, because the managing of diabetes is getting better and better, but it's a very selective group of patients. If they cannot manage a patient effectively, this could be a viable option, with the current data showing that the outcome is getting better and better. And I think it's worthwhile to explore that option.

Host Amber Smith: Well, Dr. Saidi, thank you so much for taking time to tell us about this. I appreciate it.

Reza Saidi, MD: Thank you. Glad to be here.

Host Amber Smith: My guest has been transplant surgeon Reza Saidi. He's chief of transplant surgery at Upstate. I'm Amber Smith for Upstate's "HealthLink on Air."

Is chronic pain connected to COVID 19? Next, on Upstate's "HealthLink on Air."

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

Does the severity of a COVID-19 infection predict the development of long COVID conditions, such as chronic pain? Upstate researchers were curious to find out. And today I am talking with Dr. Jamie Romeiser, who led research on this topic.

She's an assistant professor of public health and preventive medicine at Upstate.

Welcome to "HealthLink on Air," Dr. Romeiser.

Jamie Romeiser, PhD: Thank you so much for having me, Amber.

Host Amber Smith: So you set out to determine if COVID-19 severity might be a new risk factor for chronic pain. Is that right?

Jamie Romeiser, PhD: Yes, that's correct. So, when we think about chronic pain, there's a pretty well-known slate of risk factors or characteristics that might put you at a higher risk for developing chronic pain.

And some of these factors might include increasing age or having certain comorbid (simultaneous) conditions, like arthritis or a higher BMI (body mass index) or different socioeconomic factors, even. So what we wanted to know was, above and beyond all of those types of factors, if a severe COVID infection might actually be an emerging new risk factor for chronic pain.

Host Amber Smith: So what inspired you to look into this?

Jamie Romeiser, PhD: Well, it was a combination of things. And if I'm going to be completely honest, I think my initial curiosity was piqued sometime back in October of last year when I was listening to a story on NPR about long COVID. But since that time, it's really becoming recognized that some individuals who have had a COVID-19 infection, they may experience long COVID, and so long COVID is described as having symptoms that persist for longer than three months, and that didn't exist prior to the virus.

And, for example, frequently we think about fatigue or memory problems or even brain fog when we think about long COVID.

But after digging into the (medical) literature a little bit more, a commonly reported lingering symptom is actually pain. And this could be musculoskeletal pain, it could be pain in your joints or in your muscles or even neurological pain So, when I started looking into this a little bit, at relatively the same time, I was part of a few conversations with people who were actually experiencing this lingering pain after a COVID infection.

So, we thought that, you know what, this might be the right time to look at this at, potentially, a population level. So, chronic pain itself is such a huge public health issue, and if it seems like COVID is contributing to this public health issue, then we really need to be aware of it.

Host Amber Smith: What did you think you might find?

Jamie Romeiser, PhD: Well, there really were a handful of studies that found new instances for chronic of pain after a severe infection. So, we thought we might be able to see something similar at the population level, but truly we didn't really know.

Host Amber Smith: So is there, are you saying that there are previous viruses that have been connected to chronic pain before COVID?

Jamie Romeiser, PhD: There might be. But in terms of the smaller studies that we were looking at, they were actually more small, clinical-based studies that looked at severe infections from COVID and then looked at new instances of chronic pain.

Host Amber Smith: I see. Well, can you tell us about the data that you used in your study?

Jamie Romeiser, PhD: Sure.

So, in terms of where the data came from, we used data from the National Health Interview Survey. So, this is a survey that was collected in 2021, but it's been collected since somewhere around the 1950s, every year. This is a survey that's collected from the National Center for Health Statistics, which is part of the CDC (Centers for Disease Control and Prevention).

So, one of the main objectives of this survey is to monitor that overall health of the United States' population. So there's really a great deal of effort that's put into this data and the survey itself and ensuring that it's nationally representative of the United States' population.

Host Amber Smith: So, how many people were represented in the data that you worked with?

Jamie Romeiser, PhD: Well, in our study we used that 2021 data, and after we applied a certain inclusion criteria, we had over 15,000 people who met this criteria. But because of the way that this survey is collected -- so, it's collected to represent a national population -- you can actually take that number and extrapolate it to that population level.

So in a way, our study represented over 135 million people in the U.S.

Host Amber Smith: Did it include as many people with mild COVID infections as with severe infections? And did it include people with no infection of COVID?

Jamie Romeiser, PhD: It included all three, but these groups were really different, proportionally speaking.

So, the majority of people in our 15,000-person sample, actually 76% of those, reported never testing positive for COVID infection, which was a little bit surprising, but then, when you think back, this was collected in 2021, so it's easy to lose time between the beginning of the pandemic and now.

But when you talk about the rest of the people who did report having an infection, this was broken down then into people who reported either no symptoms or mild symptoms, and so that group made up about 11% of our sample. And then those who had a moderate or severe infection made up about 13%.

Host Amber Smith: And how did you define pain in the study?

Jamie Romeiser, PhD: Chronic pain in general is defined as pain that lasts for over three months. This is different from acute pain, which is usually from an injury that goes away. Chronic pain can be there either all the time, or it could potentially come and go, but it still occurs on most days.

So, in this survey, participants were asked, "In the past three months, how often have you had pain?" And people responded. Those who did respond at "most days" or "every day" met that definition of chronic pain. And the people who reported either never having pain or maybe just pain on some days, they were classified as not having chronic pain.

Host Amber Smith: So, how did you tell if it was chronic pain that was there before COVID or if it was caused by something else?

Jamie Romeiser, PhD: That's one of the difficulties of cross-sectional data, and that's one of the big limitations, for this particular study, is that we can't necessarily distinguish that particular time window.

The best thing that we can do is potentially control for that whole slate of risk factors, or all of those conditions that very likely predict your chance of getting a chronic pain and then isolate really what's happening with a severe COVID infection.

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith.

I'm talking with Dr. Jamie Romeiser. She's an assistant professor of public health and preventive medicine at Upstate, and she's done research on COVID-19 and its connection to chronic pain.

So let's go over some of the results. How did the severely infected compare with the never infected?

Jamie Romeiser, PhD: We ran these results in a couple different ways, so let me just quick tell you about the information that I'm going to present you.

We first looked at this in simply prevalence of chronic pain. So how common was this in our different groups here, in our three different groups? And then the next thing we did was to try to control for all of those risk factors and say, well above and beyond, what happens here, with a severe infection.

And then we did this third technique, which was actually matching. So we were able to create these three different groups that were really matched on their risk profiles so that we were more comparing apples to apples to apples, in a way.

So, when it comes to that first type of analysis, just looking at how common pain was in the severe group versus the never-infected group, in that broad a scope, we found that about 25% of those who had a severe infection reported also having chronic pain, whereas only 19% of those who never experienced that COVID infection reported chronic pain. So that's a difference of about 6%, which might seem small, but when you scale that to that population level, we're talking about, like, over 3 million people, so, 3 million additional people, when you take a look at this data and you control for all of those factors that usually predict chronic pain.

So, in that adjusted analysis, what we found was that the odds of chronic pain were 20% higher in the severe-infection group compared to that never-infected group.

And then when you take that analysis one more step further, and when we look at these matched groups, so matching people on all of those factors, now what is that isolated effect of COVID? And at least for the severe group, we did see about 45% higher odds of chronic pain in that severe group versus the never group.

Host Amber Smith: That does sound significant. Did your study show that COVID-19 causes chronic pain?

Jamie Romeiser, PhD: We're not able to establish that causal link with this data, and that's a really important clarification for the studies, that because of the way that the data are collected, that is a limitation.

But, after we did the matching component, after we were able to try our best to create these balanced groups, we did see that association. And so we really do think that there's a signal there.

Host Amber Smith: Well, let me ask you a little bit more about the pain that was described. Did you notice anything in common in how people described their pain?

Jamie Romeiser, PhD: Unfortunately, we weren't able to look at that specific distribution of types of pain here. We were kind of limited to what was collected within the survey, but in general, from previous literature, what we think is, this is mostly joint pain and muscle pain, pain in your hands, headaches, that type of thing.

And this type of distribution of pain should certainly be something that's examined in future studies of long COVID.

Host Amber Smith: Did you ask or look at other long COVID symptoms?

Jamie Romeiser, PhD: In our study, we didn't. So, we just focused specifically on chronic pain. But again, there are certainly other opportunities in the future to investigate those outcomes.

Host Amber Smith: Now, I know you're a PhD, not an MD, but from your research, if moderate COVID-19 infection may increase a person's risk of developing chronic pain, are there any lessons to be learned from that?

Jamie Romeiser, PhD: I think so. You know, as the broader literature stands, it does seem like anybody who has had COVID could develop long COVID.

But from this study and many other studies, it really does appear that that risk is increased for those who have had that more severe infection. So, that being said, it's really important that those who are most susceptible to that severe infection, so those who are older, those who have serious medical conditions, that they try to reduce their risk of that severe infection as much as they possibly can.

Host Amber Smith: So, trying not to get infected with COVID in the first place.

Jamie Romeiser, PhD: Right. Something that you can do to reduce that risk would be not only knowing your personal level of risk, but I'd say be aware of the general risk level in your community because that really does change over time, and you might moderate your behavior a bit due to this community risk.

And I will say to date that vaccinations still remain one of the strongest defenses against developing severe COVID infections and those subsequent long-haul symptoms, like chronic pain. The efficacy of these vaccines really does remain higher against those severe infections compared to the mild infections, but they can wane over time with all these emerging variants, so it's important to be up to date on your boosters. It's still an essential component of prevention against severe infection.

Host Amber Smith: In your research, did you come across any indication that the chronic pain that develops after COVID-19 is any different in terms of symptoms or in how it's treated than chronic pain caused by an injury or something else?

Jamie Romeiser, PhD: As you pointed out earlier, I'm a PhD and not an MD. I'm not exactly sure about that underlying biological mechanism of long COVID and those pain manifestations, but what I do know is that chronic pain and the way that people respond to treatment of chronic pain is really different in every individual.

And so it would be important to speak to your primary care physician or pain specialist to discuss those treatment options.

But we do look forward to more research coming out about this in the future.

Host Amber Smith: Thank you for making time for this interview, Dr. Romeiser.

Jamie Romeiser, PhD: Thank you so much for having me.

Host Amber Smith: My guest has been assistant professor of public health and preventive medicine Jamie Romeiser.

I'm Amber Smith for Upstate's "HealthLink on Air."

Next on Upstate's "HealthLink on Air," we'll explore a disease that causes blindness in dogs and humans.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air." Today, I'm speaking with a scientist who studies retinal disease at Upstate. William Spencer recently received a grant from the E. Matilda Ziegler Foundation for the Blind. He's an assistant professor of ophthalmology and visual science at Upstate.

Welcome to "HealthLink on Air," Dr. Spencer.

Will Spencer, PhD: Thank you for having me.

Host Amber Smith: You've done research on progressive rod-cone degeneration. Can you explain what that is and why you're studying it?

Will Spencer, PhD: Yeah, so progressive rod-cone degeneration is a disease that was originally discovered in the 1970s in dogs. It's actually the most common cause of blindness in dogs. And since it was discovered has been discovered in just about every different type of dog you can imagine. So, well over 40 different dog breeds are affected by this disease. And it was studied by Dr. Gustavo Aguirre at University of Pennsylvania for decades, this disease was, in the dog. He's a veterinarian and a scientist, and he eventually mapped the disease to a single mutation in a gene that he named PRCD, after the disease. So the gene, it codes for a protein, is called PRCD, and each letter of that gene name stands for progressive rod-cone degeneration.

So, it was mapped in 2006. So that's when he found this, discovered this new gene. And at the same time, he found that this exact mutation, and others, is present in humans that are blind. And having the disease in humans called retinitis pigmentosa.

And so, I'm studying this because there's very little known about the protein, and that's kind of my area of expertise is understanding the function of a novel protein. What does it do? How does it work? And in the effort that we could understand a little bit more about the photoreceptor cell, and maybe develop new therapies, including for this disease, progressive rod-cone degeneration.

Host Amber Smith: This is really pretty recent, at least in humans.

Will Spencer, PhD: Yeah. You mean ...

Host Amber Smith: ... the discovery of the gene that causes this.

Will Spencer, PhD: Yes, it was probably one of the most recent. And the reason for that, probably, is that this particular protein and the gene that it codes for this protein, is very small. It's extremely small. It's only 6 kilodaltons. So your average protein, let's say, is closer to 100 kilodaltons. So it's just a very small protein, and that probably made it difficult to detect biochemically in the early days of studying photoreceptor cells, because it was just so small.

Host Amber Smith: Well, can you tell me what the symptoms of PRCD are? And are they the same in humans? Or do we know if they're the same in dogs, as well?

Will Spencer, PhD: So, in dogs, it was named progressive rod-cone degeneration because there is the progressive death of rod photoreceptors, followed by cone photoreceptors. And so this is essentially exactly how the disease develops in humans. You have this progressive death of rods, followed by cones. In a human, you have 100 million rod photoreceptors and about 5 million cone photoreceptors. And most of the cones are in the center of the retina, called the macula, in a region called the macula.

And so, because you're losing the rod photoreceptors first, those are primarily on the periphery of the retina,on the edges of the retina. the symptoms would be that you get tunnel vision slowly, so you lose your peripheral vision over time. And then eventually you lose your vision completely. And so this is very similar in the dog and in the human, these symptoms.

Host Amber Smith: Is it treatable at this point?

Will Spencer, PhD: No. So, there is no treatment whatsoever for retinitis pigmentosa right now, including retinitis pigmentosa that's caused by mutation and PRCD. And so there's no treatment for progressive rod-cone degeneration in the dog or this same disease in the human.

Host Amber Smith: Can you tell us what you've learned about this condition through your research?

Will Spencer, PhD: Yeah. So, I mentioned rod and cone photoreceptors. So, maybe some of you have heard of rods and cones. The rods are used for kind of nighttime vision and cones for daytime vision.

And cones, humans have three different types of cones. You have red, green and blue. And they're like the pixels of your retina that enable you to see colors. They're called rods and cones because of the structures that are attached to these cells, called the rod and cone outer segments. the outer segments are these, they're basically antennas. There are essentially gigantic cylinders that are filled with these disk-shaped layers of membrane. Membrane, of course, is like the skin of the cell. It's like a lipid skin of the cell. you have this big cylinder that has layers and layers of this lipid membrane. And these lipids, this membrane material, serves to contain photopigment protein. So this is protein that absorbs light.

And by putting this photopigment in a big cylinder and packed with layers and layers of this photopigment, this enhances the sensitivity of your vision. So your rod photoreceptors are capable of detecting one photon of light. So that's as sensitive as they could be. And much of that is, can be attributed to this humongous light-sensing structure. this outer segment, and the arrangement of those membrane layers. And what we found, sorry to preface that with a long-winded story, but what we found is that this PRCD protein is specifically residing in that outer segment structure, in that light-sensing structure.

So it was previously unknown where this protein was or even what cell type it was expressed in. So we found that it is in the photoreceptor cell, and specifically in the outer segment. And we also found that the mutation in the protein that causes blindness in humans and dogs causes this protein to be mislocalized from the outer segment to other cellular compartments throughout the photoreceptor cell.

So this blindness-causing mutation is preventing the protein from reaching its "home" in the outer segment. And what that really means is that this little protein has some essential function in the outer segment. It's doing something there that's important for vision. So what is it doing?

Well, we made a genetically modified mouse. So, mice are a tool that we use to understand how genes work. And there's a lot of kind of tools that we can do with mice, which is why they're a good model system. And so we made a genetically modified mouse that doesn't have PRCD protein at all. And this was a great tool for us to look at, "OK, what is PRCD doing? let's just remove it and see what happens to the cell." Well, without PRCD, the light-sensing outer segment cylinder structure starts having some issues.

Now, as I mentioned, the outer segment structure is packed with all of these layers and layers of disk membranes. They're shaped like pancakes. imagine a big cylinder that's filled with pancakes. And over time, light is kind of damaging these membranes, the photoreceptor cells continuously replacing those disks. So, every day, each of your photoreceptors builds 100 new photoreceptor disk membranes. This is just a very demanding task of the photoreceptor cell. But it's doing it every day for the rest of your life, in each of your photoreceptors.

And these disk membranes are formed at the bottom of the giant cylinder. That's where they're added, so they're, each pancake, so to speak, is added to the bottom of the stack. And what happens if you don't have PRCD is that the disks, as they're being added at the bottom, start to partially fragment. So some of that kind of material is shed into the space surrounding the cells. So, instead of going into the cylinder, it's kind of like a leaky faucet where you're spilling some of the guts of this light sensor throughout the extracellular space. And this is, perhaps, what we think is causing the death of photoreceptors. There's all this membrane junk that's accumulating around them. And in other neurological diseases, when you have membrane junk accumulating around neurons, this is toxic for the cells, for some reason. It's not really understood why that is, but that's where we are. And so that's what we know about PRCD, in a nutshell.

Host Amber Smith: This is Upstate's "HealthLink on Air" with your host, Amber Smith. I'm talking with Dr. Will Spencer, an assistant professor of ophthalmology and visual science at Upstate. We've been talking about his research into progressive rod-cone degeneration.

Now, the grant you received recently is directed at your research into the role ectosomes play in retinal disease. What can you tell us about ectosomes?

Will Spencer, PhD: Ectosomes are small membrane vesicles. They're like little bubbles, like little, as I mentioned, those disk membranes -- they fragment. Well, when you have a membrane structure that breaks into a smaller membrane structure, that's released outside of the cell, it typically will be round, just like if you blew a soap bubble. It's round. It wants to be round. And these small little, round membrane structures, if they're released straight out of the cell, they're called ectosomes. And actually, in the case of, if you don't have PRCD, for example, in the mouse, that doesn't have that membrane junk that's released coming off those disk membranes -- those are ectosomes.

Now what's really kind of fascinating is that a few years ago, we found that the photoreceptor cell is kind of building its light-sensitive structure, adapting machinery that normally produces these vesicles. This is confusing, but let me just explain. So the photoreceptors' outer segment to this giant cylinder is actually a specialized type of antenna that's present on, basically, every cell in your body, called a cilia. So just about every cell in your body has this kind of antenna-like structure that can do different sensory things. It just happens to be the light sensor of the photoreceptor. And it's recently been appreciated that cilia have this innate ability to release little ectosomes from their membrane that can serve a range of functions, from removing unwanted protein cell-to-cell communication.

And what we found is that the photoreceptor cell also has an ability to release these little ectosomes. But the photoreceptor cell has evolved to block that process. So normally, the ectosomes are not released because the photoreceptor cell expresses some very specific machinery that instead of allowing that vesicle to release, that vesicle, it buds, but it's retained at the membrane. So it's kind of like it's hanging on, like a hanging chad or something. And, that is the source of building material for building those disk membranes. So, in other words, the photoreceptor cell is a hair split away from instead of building its light sensor to releasing all of that membrane material in the form of a vesicle, an ectosome.

Host Amber Smith: Well, Dr. Spencer, before we wrap up, I want to ask you what attracted you to the field of science in general, and then how you ended up in ophthalmology and visual science.

Will Spencer, PhD: I guess maybe I'm a nerd at heart. My dad was a chemist and kind of always wanted me to be a chemist, maybe, or kind of introduced me to it.

But at a young age, I remember we were, I was in grade school, and we were at an auction where you could walk by and put down bids.. And there was a microscope, something you would find in a high school biology lab. And my dad was like, "oh, that's a nice microscope," and he put down $100 thinking that was like, a $500 microscope or something. And turns out that he won the bid, and he was almost, like, grumpy that he won, which I thought was funny.

But when I was in grade school, I got this nice microscope. I mean, for a grade school kid it was a cool one. And I just remember putting pond water on there and looking at little protists moving around. I was just captivated at a young age by that.

Even though he wanted me to be a chemist, I guess it's sort of his fault, that I -- I just felt like biology was so interesting, and I had excellent high school biology teachers. They were just superb.

Host Amber Smith: So, as a visual science researcher, do you believe there's a cure for blindness waiting to be discovered?

Will Spencer, PhD: Yes, I think there's some serious progress. I think it's an optimistic future. It's really, there's some amazing breakthroughs that have happened. So, you know, with CRISPR and gene editing, there's a thorough testing process for therapies to make it as a real treatment. And the retina is really at the forefront of gene therapy.

And this, for example, could be a very promising treatment for cases of retinitis pigmentosa, including PRCD. You know PRCD is really about not having that protein in that light-sensing structure. So, that's what the mutation is causing. It's causing the protein to be mislocalized. So, if we just put back the protein that has the normal, the correct sequence, this probably would rescue the degeneration.

It's actually a slow degeneration. So, if this could be recognized early, then if gene therapy could be developed more, and as we get better and better at it, this is something to be excited about.

Host Amber Smith: Do you think that clinical trials would involve dogs before they involve humans, since this is a disease that affects dogs, too?

Will Spencer, PhD: It certainly could. Yeah. There's, I've heard estimations of tens of thousands of dogs in the United States that are blind from PRCD. I guess the one challenge is that typically you don't know if the dog has it until it's already kind of severely has a degenerated retina, at which point the gene therapy wouldn't work, really. The photoreceptors are already gone. But this could be tested in the mouse and worked out there very nicely.

Host Amber Smith: Well, thank you so much for your time, Dr. Spencer.

Will Spencer, PhD: Yep. Thank you.

Host Amber Smith: My guest has been Will Spencer. He's an assistant professor of ophthalmology and visual science at Upstate. I'm Amber Smith for Upstate's "HealthLink on Air."

Here's some expert advice from Dr. Zachary Vredenburgh from Upstate Medical University.

How can we keep our knees healthy?

Zachary Vredenburgh, MD: I think the best things we can do to preserve our knee health over a long period of time is keeping your weight healthy (and) watching what you're doing activity-wise in terms of anything that's going to have a high risk of having a major injury.

Now, that doesn't mean don't go out and play sports or be active, but some of the really, really high-impact things that you can do that put your knees at risk, I'd try to avoid that.

And I think those are probably the two biggest things. There's no really special medications or foods, or anything like that, that I'm aware of, that would help that.

Host Amber Smith: You've been listening to Dr. Zachary Vredenburgh from Upstate Medical University.

And now, Deirdre Neilen, editor of Upstate Medical University's literary and visual arts journal, The Healing Muse, with this week's selection.

Deirdre Neilen, PhD: Rob Jacques lives and writes on a rural island in Washington state's Puget Sound. He takes us through a man's determined struggle to stay clear in his poem "It's Not Dementia."

He begins with some lines from Robert Frost:

-- One can see what will trouble

This sleep of mine, whatever sleep it is.

Were he not gone,

The woodchuck could say whether it's like his

Long sleep, as I described its coming on,

Or just some human sleep.

For the life of me, I can't get used to seeing old friends

gone for years visiting me at odd moments, their being

dead no barrier at all to their attentive listening to me,

then disappearing as if they were never here beside me,

their smiles as warm as ever, their bodies as healthy

as they were long ago when we were young humanity.

The walk may be asphalt to you, but to me, I walk on

a soft woodsy duff as I reach out, not for that steel pole,

but for a black birch that grew old beside my school,

that grows there still in my timeless, faultless mind,

and even now its bold, lenticillated bark feels cool

to my hand though you see metal from where you stand.

My birdfeeders, where are they? Where did I put seed?

Here in my room, I search for small things that stray

and are lost to you, but not to me, and I need their feel

between my fingers: rings, coins, photographs, and such

that trigger scenes that seem to be current still and I'm

in them as I was back then: young, robust with a will.

Strings of long-ago conversations yet come to mind.

I try to carry them on even though I know I'm alone

and who knows who's listening? Things I wished

I'd said I say now hoping those who aren't here

still can hear, those who mattered once can know

I haven't forgotten them though time has shattered.

The past is a better place than here, and I dust off

memories to be back bright again in my world of yore

where I was whole and strong and still am in my

mind's eye where there are no stone strangers,

no corridors that lead nowhere I want to go, and I

live inside a blown reverie of what was until I die.

Host Amber Smith: This has been Upstate's "HealthLink on Air," brought to you each week by Upstate Medical University in Syracuse, New York.

Next week on "HealthLink on Air," updates on several types of cancer.

If you missed any of today's show, or for more information on a variety of health, science and medical topics, visit our website at healthlinkonair.org.

Upstate's "HealthLink on Air" is produced by Jim Howe with sound engineering by Bill Broeckel.

This is your host, Amber Smith, thanking you for listening.