Diets and Gut Bacteria: Their Connection to AMD
July 25, 2018
1:00–2:00 pm EDT
Transcript of Teleconference with Dr. Sheldon Rowan, who is currently an assistant professor in the Department of Ophthalmology at Tufts University School of Medicine in Boston.
The information provided in this transcription is a public service of BrightFocus Foundation and is not intended to constitute medical advice. Please consult your physician for personalized medical, dietary, and/or exercise advice. Any medications or supplements should be taken only under medical supervision. BrightFocus Foundation does not endorse any medical products or therapies.
Please note: This Chat has been edited for clarity and brevity.
MICHAEL BUCKLEY: Hello, I’m Michael Buckley with the BrightFocus Foundation. Welcome to today’s BrightFocus Chat, “Diets and Gut Bacteria: Their Connection to AMD.” I hope you’ll find today a really interesting topic because we’re all aware of vision health and we’re all aware of the importance of diet, but today is really interesting because we’re going to make the connection between diet and eye health. A lot of us grew up watching Bugs Bunny cartoons or hearing our parents or others saying that carrots were the key to good vision health, and today we’re going to learn that that statement may be true, but it’s also a lot more complicated.
Let me tell you a little bit about today’s guest speaker. Dr. Sheldon Rowan holds a PhD in genetics from Harvard University, and he is currently an assistant professor in the Department of Ophthalmology at Tufts University School of Medicine in Boston. Dr. Rowan has been a past grantee and is a present grantee in our Macular Degeneration Research program, and he’s done some really interesting work that looks at the interaction between diet, age, and risk-related macular degeneration, specifically taking a look at how gut bacteria affects the likelihood of getting AMD.
So, Dr. Rowan, thank you very much for joining us. I was wondering if you could start by telling us how you ended up doing what you do. Did you always want to be a scientist?
DR. SHELDON ROWAN: Yeah. I think I probably did always want to be a scientist. I started doing research right out of high school, and I would say for the most part I’ve been motivated by this passionate interest in understanding basic questions about life and how we came to be. For a long time I was studying developmental biology, which is about this question: How did we start at this simple one-cell egg and develop all of the complex features of the human body? And that kind of took me into eye research, which I’ve been doing for about 20 years. And I got to a point in my research where I wanted to take all of these fundamental discoveries we’ve made about how the eye forms and how the eye functions instead of asking about what goes wrong in disease.
MICHAEL BUCKLEY: It’s great that your lifelong interests are really coming through to help millions of people. Let’s start off with gut bacteria. I think this is one of those phrases that you hear about in the newspaper, online, magazines. You hear about gut bacteria, you hear about microbiome, but I don’t think too many of us actually know that much about it. Could you tell us, what is gut bacteria?
DR. SHELDON ROWAN: Sure. It’s funny because if we had this conversation 10 years ago, you would think I was crazy talking about gut bacteria, but it’s this idea that there’s kind of an organism that we share our bodies with, which are these countless numbers of bacteria that live inside us. There’s populations of bacteria all over our body, but most of them end up getting concentrated in the colon within our digestive system, and so people seem interested in this question.
First of all, why are they there? Are they just kind of bystanders? Are they opportunistic organisms that feed off of our waste products, or do they have an important role in our health and well-being? Among the things that we’ve discovered are kind of approximately the numbers of bacteria that live inside of us, which is at least as many cells as in our own body, yet they make hundreds or thousands of times more genes than we do. And it turns out that they are pretty critical for our health and well-being, so they do regulate aspects of our overall homeostasis.
So, for example, they regulate metabolism, they control inflammation within our bodies, and they’re really responsive to our environment. The food that we eat really gets directly translated into a message from those gut bacteria, and then the gut bacteria signals to other parts of our body, helping things function properly, and in turn we need to nourish those gut bacteria as well, to maintain optimal health.
MICHAEL BUCKLEY: That’s amazing. So, from your research, how does the gut bacteria affect the eyes and the brain?
DR. SHELDON ROWAN: That’s a really interesting question, even how we got to our research. We started the research looking at the role of diet in age-related macular degeneration. I’ve been carrying out animal studies where we feed mice different kinds of diets and then look at what happens to the eye and if any of these diets affect the risk for age-related macular degeneration. And we did really find a strong dietary connection where, if we fed our animals a high glycemic diet, when coupled with aging, our mice were getting macular degeneration-like disease. Obviously, they’re not people—they don’t actually get macular degeneration—but if we fed them a low glycemic diet they were protected from this disease, and we really wanted to start answering this question about the mechanisms.
We decided that we should probably take a look at the gut bacteria in these experiments, with the idea that what we eat is going to be affecting those bacteria—maybe they’re affecting the outcomes in terms of the eye. And so when we started to do that analysis we realized, first of all, that the gut bacteria were hugely different between these diets. We also came to realize that the gut bacteria themselves seemed to possibly get signals directly to the eye in regulating the health of the retina, and so we could actually relate different kinds of bacteria in our animal studies with their risk for macular degeneration.
MICHAEL BUCKLEY: Wow, that’s amazing. When you mentioned “glycemic,” you mentioned high and low glycemic. Is that related to sugar? How would you describe glycemic, either high or low?
DR. SHELDON ROWAN: That’s a great question. When we think of the glycemic, we think of what the body does in response to the diet and how much glucose ends up getting released into the bloodstream, and we often think about carbohydrates in this context. So, for example, high-glycemic food, such as a very processed corn starch, would be rapidly digested and converted into glucose in the body, which would then cause an increase in blood glucose. In contrast, a low-glycemic food—a great example is like whole wheat pasta; it’s a fairly low-glycemic food. It takes a much longer time for the body to digest it and release that glucose into the bloodstream. And so even though all of these carbohydrates eventually get converted into these simple carbohydrates, we think about the rate at which that happens.
MICHAEL BUCKLEY: Dr. Rowan, we mentioned the glycemic and the carbohydrates. Is this too simple of a question, but is sugar bad for the eyes?
DR. SHELDON ROWAN: No, I would never want to say that sugar itself is bad for the eyes. We know from a good body of research that the eye absolutely needs sugar, and it needs the glucose that sugar gets broken down into. In particular, the photoreceptor cells in the eye—the ones that sense the light—are extremely metabolically active, and they absolutely depend on glucose. So the eye does need—and the brain in general needs—glucose to function properly.
What we get concerned about is hyperglycemia—this concept of high blood sugar—and not the high blood sugar that happens after you’ve had a candy bar, but this idea that through your diet there may be chronically high levels of blood sugar. That’s where we get into trouble in the eye. And so a few different cell types in the eye are very sensitive to the levels of glucose, especially the vasculature cells in the eye and the support cells in the back of the eye—the retinal pigment epithelium.
MICHAEL BUCKLEY: Thank you for clarifying that. I know that diets vary greatly around the world. I was wondering, when we think about your research, do rates of AMD also vary around the world, and is there a connection between those two points?
DR. SHELDON ROWAN: That’s an interesting question. I would have guessed, if you asked me this, that yes, there would probably be really different rates the same way that you kind of see different rates for heart disease in different parts of the world. But I actually think that when people have done these prevalence studies in looking at rates of AMD across different parts of the world, they haven’t seen a huge difference.
What we know is that ancestry matters. People from European ancestry seem to have a slightly higher rate of age-related macular degeneration, even parts of the world where you might expect the rates to be lower because of the specific kind of diet. Take, for example, Mediterranean countries. We often think of the Mediterranean diet as being healthy for your heart—for your cardiovascular system—and that’s true, and it also reduces or is associated with lower rates of age-related macular degeneration. But the sad reality is that even in those parts of the world that have the Mediterranean diet that invented this, they’re eating a pretty Westernized diet right now, and they’re not seeing lower rates of macular degeneration. And places where you might expect lower rates of macular degeneration because people eat a lot of oily fishes—and we know that having more fish consumption can help lower your rates of age-related macular degeneration—it’s the same kind of thing. We don’t actually see a lower prevalence in those countries that are traditionally large fish-eaters. So there’s a lot of different factors that play in that.
MICHAEL BUCKLEY: Yeah, there’s environment and others. Dr. Rowan, you mentioned whole wheat pasta a minute ago. In general, what are some of the best foods for eye health?
DR. SHELDON ROWAN: For eye health? Of course, we think that whole grains are probably going to be more beneficial than processed grains, but the one that you want to turn back to are your multi-colored fruits and vegetables. Without question, green leafy vegetables are really eye-healthy—foods that are high in carotenoids—so ones that have a lot of color in them. Think about red peppers, think about yellow peppers; those kinds of foods are really eye-healthy. Eating fish is very eye-healthy, and then some of the other classes of foods are ones that have other kinds of carotenoids called lutein and zeaxanthin, and those can include foods like spinach or collard greens, and even some kinds of seafood can be high sources of those as well.
MICHAEL BUCKLEY: Some great specifics there. In general, some of the foods you outlined, particularly the vegetables—is there a difference between cooked versus raw in terms of the nutritional and eye health consequences and benefits?
DR. SHELDON ROWAN: The nutrition is definitely a little different. We know that when you cook vegetables you increase the availability of certain nutrients; a great example is beta-carotene and lycopene. If you think about cooked tomatoes, they definitely have higher amounts of lycopene, and we think that lycopene is probably a pretty important nutrient. But at the same time, cooking those foods can break down other heat-sensitive nutrients like vitamin C and folate, so there’s a bit of a trade-off, but I don’t think there’s a concept that one is better than the other. Whichever one you’re willing to eat is the one that people should prefer. There are foods that I cannot eat if they’re not cooked.
MICHAEL BUCKLEY: Yeah.
DR. SHELDON ROWAN: I mean, kale to me tastes so much better when it’s cooked properly. My feeling is, why not both? Cook the foods and vegetables that you think taste better that way, but also keep raw vegetables in there as well. You know, I think everything in nutrition is about balance.
MICHAEL BUCKLEY: I think you’re right, whatever gets it on your plate on a regular basis. You mentioned the change in gut bacteria and some of the negative consequences. Do those happen quickly, or is this something that’s more over an extended period of time?
DR. SHELDON ROWAN: That’s a really interesting question. I think we’re still trying to figure out how flexible our bodies are in our gut bacteria to different dietary changes. So what we know is that if you make a big change in your diet, within the order of days to weeks you can see changes in your gut bacteria, and sometimes those changes in the gut bacteria can be associated with different health parameters as well, for example, your insulin levels. Some of those changes can happen quickly. But at the same time, the body’s microbiome, especially within the gut, has a certain resilience.
An interesting study was done a year or two ago where they had people eat either completely white bread or very whole-grain sourdough bread—so one being very high-glycemic and one being very low-glycemic—and they looked at the microbiotics to see what happened. They were kind of expecting that one change to make a big impact. The surprising thing to them is that they found that the microbiome was very resilient and robust to the person based on what it was before those treatments. But even so, the different kinds of breads did affect some health parameters.
MICHAEL BUCKLEY: That’s interesting.
DR. SHELDON ROWAN: So I think it’s going to be a little bit of short term and long term. Definitely, adhering to a healthier dietary pattern is going to be better for you in the long term, but you might not notice any short-term change. And people shouldn’t be discouraged, because the same way that the processes that go awry—that means to say macular degeneration—they think that tends to happen. It may also take decades to reestablish a really robust and diverse and well-functioning gut microbiome, so people shouldn’t be discouraged if they try to switch to a healthier diet and they don’t think things are getting better within a few weeks.
MICHAEL BUCKLEY: That’s interesting. I think we all understandably want to see immediate change or immediate impact of changes that we make. We have a few questions from our listeners. Dr. Rowan, Mary from Illinois was wondering—probiotics. Do they factor into this topic at all?
DR. SHELDON ROWAN: Yeah, probiotics are definitely a factor in here. There’s not a clear consensus about how probiotics are going to affect people. I always say that there are a decent number of studies that definitely show that probiotics can affect the bacteria, especially the ones that you’re eating, within your gut. In some clinical trials people have found improvements with certain kinds of probiotics, but there’s been a lot of disappointing really well-controlled trials that also looked at probiotics with a clear expectation where they haven’t made any significant changes. With probiotics, I think they’re okay to try out, especially in consultation with your physician, but I don’t think they’re going to be a quick fix, necessarily, or at least anytime soon. I think we have a lot more engineering that needs to be done, and we do need a lot more research to know that answer for sure.
MICHAEL BUCKLEY: That’s interesting. We just got another question a minute ago that I think is interesting. The preferred diet that you talked about with the scientific research that backs that up—does any of that prevent macular degeneration from happening, or do you think this is more reducing or delaying? Just wondering about which end of this does it work or both?
DR. SHELDON ROWAN: That’s a great question. I would say that when we think about a specific dietary intervention, we’re only looking in terms of either prevention or maybe we’re looking at progression from an early form of the disease to a later form of the disease. So I’m not aware of anything that has actually shown that you can reduce the severity of the late form of the disease with a dietary change.
For example, in some of our studies we see the idea of prevention, so we see lower rates of early age-related macular degeneration, and we also see effects on the progression from early to late macular degeneration. What I think is encouraging about that is, obviously, prevention is where you want to get at: You don’t want people to even have to be thinking about, “I have early macular degeneration, oh no, is it going to progress?” This is a disease that occurs fairly late in life, so thinking about buying even a few years can actually have a big impact on what that person experiences through their life with the disease even if they do get it. So I’m a huge fan of prevention and I do think that diet is going to be a mechanism for that.
MICHAEL BUCKLEY: Yeah, that’s interesting, and I think that segues well into this question. Judy from California mentions that if you’re either gluten- or lactose-free, how does that impact getting the type of whole grains and other products that you mentioned?
DR. SHELDON ROWAN: I’m so happy that this question came up because, obviously, you can eat a terrific diet. Lactose-free diets shouldn’t have any limitations. Dairy is probably an important part of a well-balanced diet, and it’s pretty easy to get lactose-free dairy products. Gluten-free diets are a little more complicated because there’s clearly a lot of people that are suffering from either gluten intolerance or celiac disease who have to be eating these diets, and they have to be paying a lot of attention to food labels and what they’re eating.
I do have a concern about some gluten-free products because the easiest way to make something gluten-free is to over-process it. And it’s easy to go to a supermarket and find gluten-free products, but whether those are actually very good for you or not is another question. I think there are ways that you could make gluten-free foods that still use whole grains and still contain good amounts of fiber and protein that haven’t been stripped of all of these important nutrients. But there are a lot of manufactured gluten-free products out there that are like that, and I think anyone eating a gluten-free diet should be thinking really deeply about these questions of: Am I losing anything out of my food? What can I be doing to make sure that I’m maintaining a healthy diet that’s gluten-free?
And so the things that I would look for are fiber, especially. If you see a gluten-free product and it has a good amount of fiber—as much as you would expect in the non-gluten-free version—then it’s probably fine, but when you start seeing carbohydrate labels that say 24 grams of carbohydrates and 0 or 1 gram of fiber, I would be concerned that it may be over-processed.
MICHAEL BUCKLEY: That’s interesting. I was wondering if you or your colleagues that look at impact of diet on vision research—have you ever seen anything about people who are either vegetarian or vegan? Has there been anything that’s shown any increase or decrease with the folks who have those types of diets?
DR. SHELDON ROWAN: Yes. I think we need to be paying more attention to these questions about all kinds of different dietary patterns. I don’t know if there’s any conclusive research about the risk for macular degeneration. There is a decent body that says that vegetarians and vegans probably have lower rates of cataracts, so I’ve thought about whether you might expect a vegan or vegetarian diet to have a positive consequence on eye health for macular degeneration. And to me this is kind of a trade-off, because on the one side most vegetarians are eating a lot more green leafy vegetables and cruciferous vegetables—red and yellow vegetables—all these kinds of things that we want people to be eating in their diet, so they’re giving them critical nutrients. But on the other hand, you are also missing important nutrients that we do get from fish and meat and poultry, and we don’t know for sure which ones are better than others. All we can say is that maintaining a really well-balanced diet is the best way to go. So people that are vegetarians should be sure that they’re getting the full range of nutrients; either work with a physician or a dietitian to do that.
MICHAEL BUCKLEY: That’s great advice. A number of our listeners, when they’re at their eye care professional, may hear the person mention an acronym—AREDS. People have probably heard that from their doctors or on previous Chats. Is that connected to a lot of the points you’re making today?
DR. SHELDON ROWAN: I think it very well could be. What’s fascinating about AREDS—in case anyone isn’t sure about it, it’s a high dose of vitamins and minerals taken as a supplemental form. It has vitamin C, zinc, copper, vitamin E, and a couple of those pigments I mentioned before—lutein and zeaxanthin—in the latest generation, AREDS 2. What we know about what AREDS can do is that AREDS can definitely reduce the progression of intermediate to advanced age-related macular degeneration; it’s about a 25 percent reduction, which is a really significant reduction.
But what’s so fascinating to me about AREDS is that I don’t think we know exactly how it works. We know that some of those vitamins and minerals in there are working as antioxidants, and there’s no question that that’s part of their mechanism of action, but it’s not everything
For example, the zinc on its own also reduced progression for macular degeneration—so the idea is that some of these are working together to maybe enhance the function of proteins or prevent damage that’s related to macular degeneration. But you know, just on this topic of eye health and the gut, there’s no reason why AREDS might not have an effect on gut bacteria, and I think this is a great area for exploration in the future. It’s actually asking the question, “What happens to your gut bacteria when you takes AREDS supplementation? And is it possible that some of these nutrients that are being provided through AREDS might actually be changing gut bacteria?” So the short answer is that it works, but the long answer is that we’re not entirely sure how.
MICHAEL BUCKLEY: That’s great, and I think your answer kind of underscores the importance of vision research that we’ve yet to explore.
Dr. Rowan, we have time for a few more questions. One we want to ask you about is clinical trials. I think that, similar to what we talked about at the outset about gut bacteria and the microbiome, people know the concept of clinical trials. It sounds familiar, but participation rates can be pretty low. I was wondering, do you or your colleagues do clinical trials on nutrition-related issues? How do these trials work, and how can someone help advance the field of research?
DR. SHELDON ROWAN: I would love to talk about clinical trials, especially in nutrition research. I think it’s just a huge area of interest. I work at a place called the Human Nutrition Research Center on Aging, and we actually do carry out a large number of clinical trials looking at nutrition. In the case of our Center, we’re not actually ourselves doing clinical trials that look at vision as an outcome, but we’ve been participants in a number of different clinical trials, and so there’s a few different types of clinical trials out there.
Some of them are what we refer to as observational, where we just try to get large numbers of people and get information about their health and information about their diets: what they eat, how much they eat, how regularly they eat it. Oftentimes we might want to get a patient’s blood sample so we could actually measure some of those components coming from the diet, and then it’s kind of a sit-and-wait. You kind of follow these patients—in some cases we’ve been doing these with groups for decades—and ask, what are their rates of macular degeneration? What are their rates of heart disease? I mean, you could go back and try to piece together what different individuals have that may have contributed to a lower or higher risk for a certain kind of disease.
So those clinical trials are really powerful in terms that they have huge numbers and they have a lot of outcomes, but they’re not always well-controlled. For example, people can say, “Oh, I eat an amazing diet, I’m a vegetarian, I only eat salad and lean proteins,” but you know, there’s nothing that stops them from secretly going to a pub and having a burger and fries every day. So some of it is taking things at peoples’ words.
Then we have other kinds of clinical trials, and we do these regularly, where they’re more interventional trials. What I mean by that is we’ll take different groups of people.—in one group we may give them just the placebos. So if it’s a food or nutrition-based trial, we may give them foods lacking a certain nutrient, and then another group is the experimental group where we would then give them…say we want to find out, are blueberries going to be beneficial to eye health? So what we might do is we might give one group blueberry powder in their diet and another group a powder that was just like blueberry powder but doesn’t have…you know, it wasn’t from blueberries and doesn’t have those kinds of nutrients in them. And then, we usually do a shorter-term study on those individuals and we try to look at things called biomarkers, which are mycoproteins in your body, or cholesterol, blood glucose, things like that to find out if they have any effect on the body.
Obviously, we’re interested in all kinds of aspects of nutrition. I would love to actually be able to do a direct study where we test peoples’ glycemic index diet and look at whether that affects the rates of macular degeneration, but it’s hard to do as kind of a direct trial—a randomized trial—where people don’t know which diet we’re going to give them, and so you end up having to kind of rely on observational data to get that information.
MICHAEL BUCKLEY: That’s interesting. Dr. Rowan, we’re down to just one or two more questions. When we think about nutrition supplements, we had someone call in to wonder—fish oil versus fish oil supplements. Is one just as good as the other, or should somebody try to have the actual food instead of the supplement?
DR. SHELDON ROWAN: I think about this a lot. We know that fish is protective against macular degeneration. This has been demonstrated in a number of studies, but we’ve never been able to succeed in getting that same finding in the form of a supplementation. So whether it’s taking cod liver oil or specifically formulated supplements that contain, for example, the major DHA and EPA that we think are these critical omega-3 fatty acids, we haven’t really been able to succeed in any of the supplementation studies. So my hunch is that it’s probably a lot of different foods and the fish that work together, and it may be that omega-3 fatty acids are really important but only when they work together with another compound. The major ones are the DHA and EPA, but there are other forms, especially in complex foods like fish, that may be working to give you that benefit.
So I feel like that with supplements in general: If you can get those nutrients from the whole foods, you’re always going to be better off—except in the case of AREDS, where you get a dose of vitamins and minerals that go way beyond what you could actually get from food. People are probably better off getting those nutrients from the foods and supplements, the exception being, for example, vitamin D if you live way up north; in the wintertime it’s going to be really hard to keep up high enough vitamin D levels. There are certain people with genetic conditions who need to be taking supplements. But in general, you’re going to get better results with the whole foods than the supplements because there’s just so many other things in those foods that are contributing to the effect, as well.
MICHAEL BUCKLEY: Well, it’s great advice. With that, Dr. Rowan, I think one of the interesting things we’ve taken away today is just the connection between diet and eye health and brain health, and this has been a really enlightening conversation for me and I think for our listeners. I have a question for you, Dr. Rowan. You mentioned you’ve been doing vision research for about 2 decades. What do you think about the progress that vision research has made? And when you look to the next couple of decades, are you hopeful about research toward a better understanding and treating and someday curing macular degeneration? It’s a big picture question for you.
DR. SHELDON ROWAN: I think macular degeneration is going to be one of these diseases that we make amazing inroads in, and it’s probably one that we’ve made some of the best progress in. Since I started doing this research, it’s just amazing what we can do for patients with wet macular degeneration. So my feeling is that, for people who have wet forms of macular degeneration, we’re in a great place right now. I think we have treatments that can help, and I think the more that we have experience with doing those and kind of seeing what the complications are and which patients are seeing the most improvements versus those that don’t see improvements, I think we’re going to figure this out.
The bigger challenge is probably, how do you treat dry macular degeneration? That’s been a little more of a mixed bag. There’s been a lot of good drug leads that seem really promising but haven’t made it onto the market yet, and I think we’re getting close. I would say…my feeling is that the rate-limiting steps for dry macular degeneration is our understanding of what happens in the disease.
So, we can really think more cleverly and specifically about how to approach that disease. It’s taken a really long time for us to get there, but I think we are getting to that point. We have amazing animal models. We have the ability through stem cell research to now directly work with human cells, like the ones in the eye that you would never be able to get access to and do experiments on, and we can now start to really identify targets and hopefully drugs that are going to be able to treat dry macular degeneration.
I can say, from doing experimental work, that every year there seem to be incredible advances. When I go to the annual meeting for ophthalmology research it’s amazing how many clinical trials are in these early stages of asking, “Do they work in our models?” and “How can we start translating those into people?” And so I don’t know if there’s a breakthrough in one or two years, but there almost certainly is going to be a breakthrough, and it’s going to be thanks to decades of basic research, and obviously that support depends on organizations like BrightFocus.
So I’m really hopeful. If I didn’t think there was anything we could do, I would be kind of depressed working in my field. From my perspective, I’m amazed at what our nutritional interventions have been able to do. For example, in our animal studies, we’ve been able to completely prevent mice from advancing to macular degeneration by switching their diets—even fairly old mice—which I didn’t think was going to be possible. So I’m most enthused in my own research about the idea of prevention and using diet, using other understanding to do that. /But I even think that for people who have dry forms of macular degeneration there’s a lot of exciting progress to be made in the future and in the near future.
MICHAEL BUCKLEY: Well, this is great. You’re optimism is infectious and it’s contagious. At BrightFocus we’ve been very proud to work with you on a lot of this research, and it’s really exciting. I just want to thank you for so much of what you’ve shared today. I think you’re exactly right. It gives people a sense of hope of the power that diet can have over your health and the things you can do about it. I think it’s a very informative Chat, and so I just want to thank you. And to our listeners, thank you very much for joining us.
Dr. Rowan, thank you very much for being so generous with your time and so specific and so helpful to all of us.
DR. SHELDON ROWAN: Thank you so much, Michael. This has been a lot of fun to do, and thanks to everyone who called in with questions. That was great.
MICHAEL BUCKLEY: Alright. Thank you very much, and this concludes today’s BrightFocus Chat.