The Science Behind Pediatric Retinal Research with Dr. Kenneth Mitton and Nicole Giudici

Luisa Recchia: [00:00:00] Welcome to Through Our Eyes, a podcast from the Pediatric Retinal Research Foundation, where we share real stories, expert insight, and meaningful conversations for families navigating inherited retinal disease and vision loss. In today’s episode, we are joined by Dr. Ken Mitton and Nicole Giudici for a thoughtful conversation about the patient and family experience, the importance of support, and the roles of research, care, and connection along the journey.

Whether you are a parent, a patient, a loved one, or someone simply wanting to better understand this community, we hope this conversation reminds you that you are not walking this road alone. There’s information, there’s hope, and there’s a community ready to walk beside you. Let’s begin.

Nicole Giudici: All right, Dr. Mitton, are you ready? Just to kind of level set the playing field, [00:01:00] why is research at the lab level so important in the overall picture when you talk about research and development of drugs for rare diseases, other diseases?

Dr. Kenneth Mitton: The reality is in the field of medicine, for example, uh, everybody knows there’s lots of drugs that are used for all kinds of things. People take drugs to keep their cholesterol lower if they have a problem with that, uh, maintain blood pressure, and then there’s other drugs used more acutely in the moment for specific symptoms.

Every single one of those chemistries really started off in an academic research lab in a college or university. The biochemistry about them, how they worked. Often the research isn’t being done specifically looking for a drug or a treatment. It’s just basic scientists trying to figure out how an organ works normally or a tissue works normally, how a retina works normally.

[00:02:00] And then when you kinda think you understand how it works, you get some handle on what isn’t normal and why is it broken in the case of causing a problem or a disease. And as people are doing that, they’ll discover things that can be useful. And so things like a therapeutic drug, they all start in an academic lab that wasn’t necessarily doing research with the ultimate goal of developing a therapy.

And so when cholesterol drugs came out really in the ’60s and ’70s that came out of research that was done in the United States by some scientists that were just trying to understand how cholesterol was made, uh, by cells of the body, and they were figuring out that biosynthetic pathway, and they were finding the enzymes that they thought that were doing it.

And to just scientifically work that out and to prove it, they developed and used chemicals to inhibit some of those enzymes. Uh, [00:03:00] their goal was just to figure out how cholesterol biosynthesis happens, which they figured out. But along the way, they developed some tools that they realized could also be well-tolerated by rats and probably people too who had high, high cholesterol and, and high risk of heart disease and those became the statin drugs.

And that’s typically what’s happened with a lot of things that we benefit from in medicine is they come out of letting scientists, uh, have funding bodies that they can get support from with usually the investigator, it’s their own curiosity and their own expertise. They come up with their own idea.

They make a proposal. They compete for some grant funding, and if they get it, they do that research project. And things just accidentally … it’s serendipity, uh, having a lot of, uh- Educated people spend a lot of time just working on stuff and discovery happens. And so that’s why it’s important to have [00:04:00] research, what you call basic science research.

And so over 95% of anything you get prescribed to you from the pharmacy has originally come out of knowledge that, that, that comes out of a lab somewhere, uh, in academia

Nicole Giudici: That’s so cool. We talk about, it takes a village to really help everybody do everything, and you had mentioned that there are scientists that are working in the labs to learn all of this stuff.

But they also have a village behind them, and sometimes we don’t understand who all is their village. Can you give us an idea of who helps these scientists when they’re doing this research? Is it students? Is it trainees? Like, who are the people in the lab?

Dr. Kenneth Mitton: Yeah, so there’s students. So, actually some students are just walking by right now in the summer undergraduate program in eye research that are in our lab.

They’re going off this afternoon to practice isolating mouse [00:05:00] retinas from some little mouse eyes, because we use those in our research with norogen testing the therapeutic we’ve developed based on making norrin. And, uh, and so, uh, you know, that’s where people start. In the ’80s they were…

I was them in the ’80s. You get into a lab somewhere. Uh, so there’s, at a, in a university, what a university really provides, and our colleges provide, is not just training in subjects that are just brain, memorization and knowledge, but they also, we give spaces like this, give you a chance to bring somebody in hands-on and say, “Okay, here’s how a lab runs.

Here’s what things cost.” Labs are kind of like little businesses. You get a finite amount of money, and you have to know how it’s being spent. Uh, you have to fund people to be working with you. And so at the university level, there’s support staff within the university in our research office, who help [00:06:00] do accounting.

There’s financial systems at the university that, that manage a- accounting and the building infrastructure. All of these things in the whole university, you can keep going on and on and on make an environment where research can happens i- i- in this… So I’m sitting in the pediatric retinal research lab that, that your foundation has made happen through, uh, through its donors.

And, uh, you know, it’s over 10 years now that we’ve had this lab. It’s doing what it was intended to do. And, uh, and it provides a space though, not just for doing the research, but it, it’s also where lots of people get trained. You know, like maybe 100 students have been through here by now, and medical students who work with me when we do s- some sequencing of associated retinal consultants, uh, patient families for FEVR and Norrie disease genes by doing some of that here, the med students and the science students get to see what’s under the hood.

How do you do [00:07:00] DNA sequencing? What do you do with the DNA? How do you make those sequencing libraries? When you get that information, what do you do with it? And, uh, you know, what tools do you use on the web or on your computer to get information that you can use to now, uh, hopefully maybe have solved why that family has FEVR.

And so, uh, training on the job is also something that we have to try to do at the same time as we do original research. And so, there’s graduate students in labs that are getting graduate degrees. Sometimes we have post-docs, people already have PhDs. Uh, there’s just so much to learn even as a biochemist.

You know, I did post-docs at Virginia Tech and the National Eye Institute at the NIH and the Kellogg Eye Center at the University of Michigan. I spent about… After my PhD, I spent another, six to seven years post-docing to sort of just get enough [00:08:00] enough confidence and enough, uh, expertise and enough ideas to get my own lab as a faculty member here.

Uh, and that was in 2001. And so all these people are being trained all the time, and, uh, hopefully it just keeps continuing, uh, because you need, you just always need the next generation to keep moving things along. And so, uh, within the ERI too, there’s a few people in office support staff that, you know, c- we have a floor and a main office, an administration assistant.

And so, uh, that and the support staff and then the students that are learning other people in your lab that are doing the work with you. You can’t do it all yourself, or you could only do a little bit of it at a time. And then we also, uh, you know, we just went to the ARVO meeting, the Association for Research in Vision and Ophthalmology.

It was in Denver this year. Spent a week there. There, 12,000 vision scientists from all over [00:09:00] the world come there, and so that’s where you get to meet and talk with each other, learn some things that you’re y- all in one place. Find other colleagues you can work with. Some of the knowledge I’ve applied to figure out how to make Norrin in bacteria, or to figure out how the blood-brain barrier’s altered by Norrin or VEGF in cells that we grow.

Some of that knowledge comes from experts who are in Germany, in the Netherlands, in Canada, in Australia, uh, in Japan, and, uh, that’s important, uh, in the worldwide community. All scientists usually belong to some greater national group and some connections worldwide where you just have a lot of people like you who speak a different language, but you’re all have the same interests.

Nicole Giudici: I love that you mentioned that we have to grow and develop the next generation of researchers.

And I know PRRF supports the Super Student [00:10:00] Program, and we’re really proud of that.

Can we talk a minute about w- what that really means when you have the Super Students that you support, and you bring them in and they do the summer program with you, how does that help develop the next generation of researchers?

I imagine exposure is something that maybe they would have otherwise not had if they-

Dr. Kenneth Mitton: Yeah. So i- if, if someone doesn’t have a chance to, to work in a lab they won’t … You can memorize biochemistry pathways and things like that, but … You can read about people doing polymerase chain reaction, PCR.

You can learn and read about techniques and things that are done in labs, and spectroscopy and analysis. But you have to really go and do it to really appreciate how it’s done. And if you can get into a lab when you’re an undergraduate, the, uh, you know, the earlier you start, it’s like anything, it’s learning stuff and experience takes time and the passage of time.

So [00:11:00] the earlier you can get onto it, the better. If you’re gonna go to grad school in the future and, and be even more in a lab doing graduate research, if you already have skills in the lab and know how to do some sophisticated analysis, that gives you a great head start compared to graduate students that will just be maybe going into a lab for the first time as graduate students.

And so just getting an undergraduate science degree doesn’t guarantee that you’ve ever had lab experience. And, uh, and it’s not always necessarily that we’re just training vision scientists here. Probably most of the students that we train don’t necessarily go into vision as a field. Many of them do.

Many of our first super students here from the early 2000s have long graduated, and some of them are ophthalmologists, and some of them are research scientists with PhDs. Some of them are managing aspects of healthcare systems, [00:12:00] and certainly have gone into medical fields. There’s some early students that are ER docs, uh, neurosurgeons and and people that have gone even into management of business and gotten advanced, uh, management degrees, and they tend to work with biotech companies ’cause they have a science background.

So all these people, uh, if they can start at the undergrad level, it helps them compete for maybe sometimes a limited number of spots in medical school, dental school, optometry college, any graduate school in science. It just helps them sometimes get noticed and to get that interview.

But also they’re gonna be a little bit more self-confident, which probably comes out when they go and interview because they’ve worked on stuff that seems kind of amazing to do sometimes, and you get to do it hands-on, and you get it to work for you, and you kind of understand that process.

And then what that will seed in some people is, depending where they go as [00:13:00] they mature into their different careers, if there’s research involved you know, if you’ve never done research at that stage you might not… There’s no reason for you to suddenly pick it up. But if you’ve kind of been involved in research and you realize, “Hey, you know, in my field, this is a, there’s a…

I’m sure there’s te- technology to solve this problem. Here’s something we could fix up,” that’s a research project, and, uh, and we have some idea of, of how to do research. A- a- and we certainly now know people we could contact, uh, and, and ask what should we do first and next and, and get help from.

And so that’s the advantage of having people in a lab early so that they… Because a clinician can do research, uh, within their practice. And you can also do research in a very obvious lab bench space like this as well.

Nicole Giudici: This is so interesting. I’d love for you to provide some color around the timeline for [00:14:00] research.

When you talk to people who are supporting research endeavors, sometimes it’s thought to be a sprint, and y- we give money, the money goes to the lab, and within, like, a year or two, there sh- there should be a product that does something for someone. But that’s not really true. Can we talk about the marathon journey of research and how long it really takes from the time you start in the lab till something really comes to fruition?

Dr. Kenneth Mitton: Yeah. Because we’re, we’re kind of working in an area, and if you’re talking about medicine or medical problems often it starts off with you know the physicians know there’s the symptoms of a disease and what it does in, in, in the organ system and, they know that you’re going blind.

They know that maybe the photoreceptors are being affected or your retinal vasculature is a problem. They might know things like that, but the underlying causes that are causing that aren’t known at [00:15:00] first. And the first thing is to spend some years figuring that out. Uh, a- any one person can only work on one experiment at a time.

And even when it comes to doing things like when… So people, with this broadcast, a lot of people and families will have heard of norrin and Norrie’s disease. You know, in the… As you go into the 1980s, scientists are just finding that there’s a w- they know Norrie’s disease and this is inherited.

They know there’s a gene somewhere in the X chromosome. It takes some years for people to find what part of that chromosome it maps to, and then to actually find a gene and a protein which seem to explain that disease, and it was norrin, a growth factor for retinal vasculature. And if you had a version of it that doesn’t make a functional norrin protein, you’re not growing a retinal vasculature.

As you go into the ’90s, people figure out, oh, there’s this norrin. They know it’s probably some [00:16:00] type of a, of a h- of a protein hormonal growth factor. But you still don’t know what does it do? Uh, I mean, how does, how does it make retinal endothelial cells grow? Uh, and so other people have to do experiments to find out, oh, it binds a protein, a receptor on a cell, and it’s called Frizzled-4.

And then other scientists over the years, even as we go into the 2000s, it takes some more time for people to find out that it has a complex receptor. It has this protein called Frizzled-4, and it has another one called LRP5, and then it has a third one called TSPAN12, and all three of them kind of grab norrin together, and that’s why retinal endothelial cells respond to this growth factor and, and you don’t need that to grow blood vessels in the rest of your body.

Uh, and so there’s… That takes years literally. Y- you go acr- you go through 15 years of [00:17:00] research just to sort of, okay, now we have a system. Norrin, it has receptors on a cell and then there’s signaling in the cell that happens after that, and people discover those components too. And so these are being done by multiple labs in, in the United States and in Germany and in Canada.

And that’s before you maybe think about using it therapeutically. And then we kind of get up to around… I mean, Dr. Trese, when I met him in around 2002, he, he already wanted to know. He was always already pretty sure, uh, Michael Trese and, and Kim Drenser, who he was just had recruited kind of at that time, that, that norrin surely must be useful therapeutically to repair a damaged retinal vasculature.

He had just had a feeling about that. But it’s not until we really get till about, uh, you know, 2015 that, you know, we said, “Okay,” you know, he gets together with me, and I’m a molecular biologist. I, I do different things. I’m a broadly trained biochemist. And with their [00:18:00] clinical insight and my skills in the lab and our…

and all of our knowledge of the retina we realize that we can probably make norrin ourselves in bacteria to get the quantities we need, and, uh, it will be hard to make, uh, and every protein’s different, but we could do that, and that’s kind of when that starts. And then some preliminary research for a couple of years goes on, and, and we kind of get to around 2018 or so by that point where we apply for a NEI/NIH, uh, small business technology transfer funding.

That’s what Retinova Therapeutics, uh, did the company for… that, that was started by our colleagues at Associated Retinal Consultants. And, uh, and you kind of do a phase I study, and that’s with our mice and, and making the… Making, could we make the protein? Could we refold it? Would it behave like norrin?

Could I inject it into a mouse [00:19:00] oxygen-induced retinopathy model where we test to see that norrin is active, and it helps the vessels grow back faster? And then we do some more work on cells. That takes, you know, a couple of years. You know, so now, you know, they… That works, the feasibility study, so they apply for what’s called a, a second stage of the, uh, SBIR, Small Business Technology Transfer.

That’s what we’ve been working on with them for the last two years. So now we’re getting up to, as you know, 2026, where we’ve where they now have norogen made in kind of a j- a good manufacturing practice, large scale company that does that, makes those products. Hopefully, that will be the grade of product they can test and use on humans.

And that’s what we test with the mouse model still and on the cells in the lab, all this preclinical research. And so, so as an idea, you can see that really things start way back [00:20:00] when somebody discovers norrin is the gene that’s responsible for Norrie disease. And that… So now you’re talking 30 years from that to now.

And so maybe that gives you an idea of i- it- it does seem like things go slow when you look back, but people are very, very busy doing little experiments every day, and time just has to go by. And, uh, and then you learn from each other, and i- in- in our case, we’re the ones that decided to get the norrin made to use norrin itself as a therapeutic compound.

And the, the signaling system that involves norrin is now becoming of interest to drug companies that already make other drugs. And so they’re, they’re making different chemicals to try to tweak or activate that signal to also test to see if that can help, help reduce leaking, uh, i- in retinal diseases a- and help to shore [00:21:00] up the, uh, the blood retinal barrier.

In the case of Retinova Therapeutics, they’re actually using norrin itself which I like as an idea because norrin’s in your retina naturally, and we’re just letting mother nature tell us how it works and using that chemistry to make it work. And so we’ll be finishing up that second stage of testing really just in a couple of months here.

It works fine the way it’s supposed to when we test it, and then… But now the company’s at the point where, they’re working towards, and as you know, Dr. Drenser, their goal is to get that particular compound into a, a clinical trial and FDA applications as an investigational drug.

We knew that was the goal, over a decade ago. But it’s interesting now that we’re at that point. Uh, so when I look back, I think, wow, you know, we, uh, i- it seems to have gone fast, but it took many years. And, and a lot of that [00:22:00] was possible because this facility here was really available to us by 2012.

And so, next thing I knew, it was 2022. That’s a decade, and now we’re past that. And so, so a lot of the equipment that’s here that we test with the cells and with the imaging, the mouse eyes that’s all here. That was all possible because of the Pediatric Retinal Research Foundation’s donors.

And so we’ve used it constantly to apply it. A- and the other thing you don’t… We, we will do some sequencing. We’ve made some custom sequencing tests to do sequence some subjects and families from Associated Retinal Consultants. That’s possible because of this facility as well. When this is established, it also helps you get other people to throw their hat in the ring, as it were.

So, you know, it was eas- you know, a different foundation in Michigan called the Carls Foundation that just likes to support anything that helps [00:23:00] children. You know, I said, “You know, we’re, we’re kind of doing a sequencing, DNA sequencing, but we could really use this instrument to quality control our sequencing chemistry.”

Uh, you know, and they gave us funds for that. And so, uh, so you just get… Y- There’s a little bit of a community involvement and your, your own state. It’s very important to have contact with supportive people and organizations that are within your state usually, just ’cause it seems to, you know, people do like to interact with each other.

And I like having progress. We publish science that we do. That’s very important. And always provide those papers to PRRF. And, and also the posters where numerous students and medical students present information on research they’ve done here at the ARVO meeting or at or at other medical meetings and, uh, and get used to communicating research [00:24:00] And so, these people all continue on to do stuff.

You know, and now we’re all old enough in our careers that we have people that we trained very young are now in their careers, and that’s all possible for a lot of those people because of this, this, uh, this little facility. And-

Nicole Giudici: That’s so awesome …

Dr. Kenneth Mitton: yeah, some of the very first med students in the first-year class at OUWB, Oakland University William Beaumont School of Medicine, when it started back, like, in 2011, a couple of those students that went into that early program were some of the first super students who worked in this lab when it was first available and they’re, they’re physicians now,

Nicole Giudici: that’s awesome.

Dr. Kenneth Mitton: You have ripple effects that go out well beyond, uh, these walls, and I think it’s important for people to know and understand that. Nobody can get anything done on their own.

Nicole Giudici: And just if people aren’t familiar with the posters [00:25:00] versus publication manuscripts when research is done and you get preliminary findings or these are new findings, typically someone from your group or the researcher really puts together a poster, and they take it to these big conferences and present it to their peers. And that’s kind of the first step before it gets to a paper or a manuscript that gets published in much greater detail.

Dr. Kenneth Mitton: Yeah, and that’s exactly true. And we used to get these printed out on paper. We tend to get them printed out on some nylon fabric so they’re, they’re easier to fold up and take with you. But you get a nice, four by five foot poster printed out in great, great detail, uh, which is kind of like a miniature version of a paper all on one side of a big poster.

It, it has a little abstract to explain the whole thing, and it has a little bit of introduction, some results you want to show, and there might be some tables or graphs or images. And, uh, and then really you put on some conclusions. [00:26:00] Uh, and you, you give it a good title so that the title makes sense. And so as somebody’s…

So you go to an ARVO meeting you know, we were in the Colorado Conference Center, uh, and you can look that up in Denver. It’s a… It can hold 12,000 people in it. So when you’re, when you’re in the poster area, display area, there’s literally 1,000 posters up every day. And, uh, and in different rows, grouped by categories.

And sometimes you’re manning your poster, but often you’re also walking down these rows of related subjects, meeting other scientists and their students at their posters. And you, you get to take in a lot of information that isn’t published yet. And, uh, and so y- you learn things and you build relationships with people that you might collaborate with as opposed to both wasting your time competing with each other.

And so, that’s another value o- of having the meetings. But yeah, students will [00:27:00] go and take a poster. They’ll be a first author. And if they do that, I try to get them to a meeting. And, uh, and so, so sometimes, uh, i- if they’re doing something that comes out of the PRRL lab we’ll, we’ll support them sometimes with a little mixture of funding support from here as well as maybe from some of the other grants that I have.

You know, we try to get med students or students to a meeting without putting them in debt. Uh, you know, that, that would be mean. And so numerous, numerous posters happen every year. So we had, from our group here, we had three, three students, uh- Wow … two med students and OUWB. O- one, one, one subject was on FEVR, uh, sequencing, uh, genes.

And now some of the students have our genetic data, and they’re going into the ARC clinic, and they’re getting the clinical data, and they’re putting that, those stories of the clinical data together with the genotypes, and so they can write papers on that. And so they- They get a [00:28:00] chance to write manuscripts and me and Dr. Drenser get a chance to edit what they write. And so they learn how to write, uh, a scientific manuscript. So those are … There’s a few of those in progress right now. I have another student who’s, uh, who is really is an undergrad here, worked on sequencing. He’s a med student too, but he’s just finished his first year at Michigan State University’s Medical School, Savio Krikor.

And so, we did a poster on norogen being tested in the mouse OIR model. And, uh, and also some improvements to that model system for people who use the model to make it a, a, a more efficient model to use, um, researchers, because a lot of researchers working on retinal vascular diseases use this model for their research.

And so we had a poster on that. Sometimes you don’t know. You won’t be able to predict what your posters will be next year, because you literally … Uh, summers are very important, because a lot of things that we kind of do this summer new by the [00:29:00] time we get to December, it’s time to submit an abstract to the ARVO meeting.

And so, uh, so students that I have working now, we might get something on a poster, and those will be the 2027 ARVO posters. And so that happens all the time and that gets students to a meeting. It gets them to see how, how to get organized in a big meeting. Going to a small meeting of 200 people, you can all sit in the same room and watch all of the same talks, but when you go to these meetings with 12,000 people at them you have to

You can’t go to every talk. You can … Y- so you have to learn how to choose what you’re gonna see and learn how to meet people, interact, and then … And so you learn, and then also teach other people what you know. And so, uh, that’s a very rejuvenative thing. Going to the PRRF family weekend conference thing, which happened just kind of before ARVO, that’s kind of nice, uh, [00:30:00] you know, ’cause you, you do academic stuff.

You do research all year. You’re worrying about grant funding, all kinds of things that scientists have to worry about. When you have these positive things like the family conference, uh, which helps remind you what the purpose of everything is really, you know, to help people. And, and then you go to the ARVO meeting, where I just sort of leave this space, and you spend a week talking and meeting and learning with people.

That’s really good for a scientist, because it kind of resets your brain, uh, kind of gives you another boost of juice for the next year. And, and so all these human interactions are really, really important and constructive.

Nicole Giudici: That’s awesome.

Dr. Kenneth Mitton: Yeah, so, so I didn’t really know what to… I mean that we would make this lab and apply it bench to bedside, which every scientist would like to think they could do, uh, that’s very hard to do, to get something out of a [00:31:00] lab.

I’ve been happy to be involved with my clinical colleagues because when you work together as a team, th- that’s how you get things, uh, to the bedside. Y- you need to have physicians involved with people that are just scientists, and they have to find a way to work with each other because either…

They’re both an essential half to getting it done.

Nicole Giudici: Agreed.

Dr. Kenneth Mitton: And so that’s what I’ve learned about it. And so I also I, I’m, I’m not in the company, and I gave them my IP for, for no compensation. You know, it’s hard enough to get a new drug invented and made and into, into actually being produced and distributed.

That’s a very big challenging job. That group of physicians have done things like that before. What I also like learning is I’ve learned and seen the process of what they have to do all that, and so I try to take that as an educator and [00:32:00] include that in when I teach. So I also get to tell undergraduate students and graduate students in my science of vision class, you know, when we do bench, you know, how do you get research out of a lab?

How long does that take? Who gets involved? Where does the money come from? Several sources. I- if people have some idea about that when they’re working in their career, they might go, “Oh, I know that’s a possible thing,” and, uh, you know, “We could do that too.” And that’s what you want people to believe is that, “Hmm, you know, maybe we could do that too.”

And, and when I met Dr. Trese and Dr. Drenser, you know, that’s what happened to me is I go, “Oh, maybe we can do this,” because, you know, uh, Dr. Trese’s done that before, and he doesn’t really see walls, he just says, “Well, you know, it’s… We’ll build a ladder for the wall.” And so, and then you just want to train young people to think the same way.

And, uh, if people put the time in, [00:33:00] things happen. So I’ve been really happy with seeing all the stuff that’s come from it and it makes it more fun to go to work every day.

Nicole Giudici: I love that we get an opportunity to bring the audience along for this journey in research.

As human beings, we’re really emotionally tied to when things are good- Mm … and really let down when we think things have failed, and research is one of those probably very rare places in life where people can be excited about a failure in research. And just for a background, when you start doing research, it starts with a question.

You have a question, and you think that the answer is going to be whatever it’s going to be, and that starts off your research.

Dr. Kenneth Mitton: That’s right.

Nicole Giudici: And a lot of research fails. More research fails than succeeds. But as a research community, even failures in research are-

Dr. Kenneth Mitton: Oh, yeah.

Nicole Giudici: … Kind of wins because you’ve learned something.

It’s moving the needle. It’s- Yeah … jumping you to a new way. [00:34:00] So it’s a little different way of thinking than we’re used to, but th- failures are welcomed in research ’cause it’s answered a question one way or the other.

Dr. Kenneth Mitton: Yeah, sometimes the, y- you imagine what you think is how a system is working, and you do some experiments that are s- to test that and to prove that that is doing that or not.

And sometimes you find out, the system tell… You, you learn that it’s not working that way at all. And then you have to steer, i- it… You then have to face a different explanation. A- and that eventually leads you to finding out how it really works. And so that, yeah, that happens all the time. I do research with VEGF, vascular endothelial growth factor, and some signaling it does. And so you, you, you study some aspects of how it works on human retinal endothelial cells that form the blood vessels. And some of the things that we expected to see when we, when we do some testing with those [00:35:00] hormones, but then s- there are some things that surprised us.

And so, some- sometimes the dogma says this other pathway is gonna be involved, and you use a chemical to block it, and it doesn’t seem to stop the effect. And so that tells you, oh, it’s not using this pathway like we supposed, so now we have to go finding the one that it uses. A- and so experiments happen like that all the time.

But what a scientist learns to do is try to design questions which give you a test to do, but it’s okay if it has a different answer. It seems like scientists are changing their minds all the time, but they’re not. They’re changing their current model.

Their current hypothesis and model on how something is working, uh, we test it, and then our model changes ’cause we have to adapt the… We have to adapt to what the real results tell us. And then when you do enough iterations of that, you go from not knowing something that was just a black [00:36:00] box to having a pretty good idea of how it works.

And once you have a pretty good idea of how it works and where all the parts fit in, you then understand why it’s broken, and then you can start to think of how to fix it, and that’s kind of the process in a nutshell.

Nicole Giudici: I think this conversation has been great. We have learned how long research takes, why it takes so long.

It’s really expensive. Things don’t always work out like we think they’re going to work out, but that’s okay, ’cause it helps us figure out how things are gonna work out. Mm. And we’ve talked a lot about the medical community and the scientists and all that they bring to research and development and, and moving science.

But I think we’d be remiss if we didn’t acknowledge the incredible contribution of the patients and their families and all that they provide in research. Because none of this would ever be possible without the patients trusting the clinicians, the [00:37:00] scientists, and being willing to participate in clinical trials, and being in trials that might not work out.

And it’s a lot for the patients, but we are so appreciative, and we very much appreciate all that you do and all that you give as a patient to further science.

Dr. Kenneth Mitton: Oh, for sure. Yeah, so, so numerous OUWB medical students have done what’s called their Embark research project with us, and they’ve all, all been involved in this lab.

And the first one was Austin Knapp. She was one of the first people to be dabbling imaging rats with me with our OCT over in our imaging room way back maybe 2012, 2013. You know, she’s a retinal physician now.

And so, uh, so she was my first medical student from our program here. Coming in this summer just because the, our, the first years are just finishing up near, uh, more into June, will be number 20. [00:38:00] I’ll be mentoring my number 20 OUWB Embark medical student who will help out with some of the human sequencing data stuff we do, and also probably helping with some of the final analysis we’re doing with the most OIR model, injecting the norogen, uh, that, uh, that Wendy Daley in the small, uh, Retinova protein lab, which is also on this floor.

You know, she walks over with the norogen ready to go, and, and we inject it and test it. And so, uh, so that’s the 20th, uh, medical student just from our medical school who have all been trained only because of resources and facilities that were made evol- made possible by the PRRF. A- and DNA samples that families at ARC bothered to give and consent and let us to do sequencing and research with.

And so, and, and that’s all had an impact. Uh, we’ve done publications on, we’ve [00:39:00] learned the types of variants that can cause, new variants that can cause FEVR or Norrie disease and, and retinoschisis, and we get that information out to educate people in publications. Uh, and so, uh, they have directly contributed to the, to this buildup of scientific knowledge that we like to do as human beings, is just build up the knowledge base.

And so, uh, it, it would not be possible without any of those, a- any of the supporters or the families. Wouldn’t be possible.

Nicole Giudici: Well, I hope everybody has enjoyed learning about the village that supports and moves science forward in research, and we look forward to connecting with you guys again.

Luisa Recchia: Thank you for joining us for this episode of Through Our Eyes. A special thank you to Dr. Mitton and Nicole for sharing their time, insight, and perspective with us. Conversations like this help bring greater [00:40:00] understanding, encouragement, and connection to families affected by pediatric retinal disease and vision loss.

If today’s episode resonated with you, we invite you to share it with someone who may benefit from hearing it. You can also learn more about the Pediatric Retinal Research Foundation, our work, upcoming events, and ways to get involved by visiting prrf.org. Until next time, thank you for listening. Thank you for being a part of this community.

And remember, through research, support, and shared stories, we continue moving forward together.