New 'atlas' of macula to develop understanding of disease

[00:00:03]So welcome everyone and thank you again for joining us at my macro and me. My name is Ed Holay and I'm the chief exec of the macular society and it's my pleasure to be hosting us this evening and our topic to this evening is the new atlas of macula to develop understanding of disease. So we're joined by PhD student Kuba Kayak Kuba Kubakayak apologies from UCL who will be discussing the new atlas of the macula.

[00:00:29]he and the team have been developing to better understand macular disease. Kuba is a third-year PhD student at the UCL Institute of Opthalmology where is part of Dr. Colinchu's lab. His research focuses on age related macular degeneration with a particular focus in using advanced imaging and molecular techniques to visualize and map cells in the eye to better understand how they interact. And the purpose of this research is to produce a reference map of what the eye is supposed to look like and what's happening in a person with macular disease. Kubra is just one of several PhD students funded by generous donations from our supporters. Since the exception of our PhD program in 2013, the Max Society has funded 31 PhD studentships worth more than 3 million pounds. students like studentships like Kubers enable vital research and help give scientists the best possible start to their research careers. So, thank you to everyone who supported uh research like Kubers. We're delighted to welcome Cuba this evening to tell us more about his research and how it could help transform our understanding of macular disease. And as always, if you have any questions, please type them in the chat and then once Cuba is finished speaking, we'll go through as many questions as we can. So, over to you, Cuba. Thank you.

[00:01:50]>> Thank you so much for the introduction.

[00:01:51]Yes. Uh my name is uh Kuba as I was uh introduced. Uh and I'm just going to share my screen. So that should all be working now. Um it's genuinely a great privilege uh to be able to present here to you some of the work that I've been doing uh on the macula uh and on on the retina as well. I was I have to say I was thinking for quite a while. What's the best way? what's the best title to really grasp what this webinar is about?

[00:02:22]And uh I I decided on mapping the macula and I think that really encompasses exactly uh what our goal is which is as I've been introduced slightly in the in the introduction. um we really want to create um a detailed map of the human macula that has the most detailed map that has ever been produced. And we hope that by doing so we can help researchers better understand what is happening in AMD uh and why certain diseases develop differently from one person to another.

[00:03:03]better understanding doesn't necessarily immediately mean a cure. So I do want to make that fairly clear. But every major advance in medicine starts with understanding the disease more clearly. Uh and I think that's something that over the last uh few decades really we've really wanted to make sure that we're all from a strong foundation and I think that's some of the work that I I'm going to show here. Now, I've worked a lot with microscopes. As you can see, there's a lot of very colorful images towards the back. And what I've been doing primarily is looking at the microscopic features of the retina and the macula to really gleam into the details that have been previously essentially inaccessible.

[00:03:51]And over the course of this webinar, I'll talk about the age related macular degeneration.

[00:03:57]uh how we can grasp a deeper understanding of that and how we have been able to technologically uh discern some of this that development in technology cuttingedge technology has really allowed us to to uh map the macula uh in a way that was previously not possible and as a bit of a bonus as well I will talk about my experiences and journey doing this research uh over the last few years. Um, so yes, I'm a PhD student. Uh, and I was generously funded by the macular society for the last 3 years. So I'm almost at the end actually. Uh, I've got about 2 months left. Um, and as I've already hinted, I'm a scientist primarily, um, not a clinician. So my work is focused a lot on research as opposed to direct clinical care. But I fundamentally believe that some of the things that I'll show you here um will really help impact clinical understanding of AMD and be a key stepping stone for that further advancement as well.

[00:05:06]Okay, let's go through the project. So we've been aware for the last 30 years or so um probably more uh with a lot of the research that have been done in age related macular degeneration um that although we've made loads of progress and great progress the actual current treatments still remain imperfect for a lot of things. So if we were to really look at the big improvements um in treating macular disease, we can realistically look at one big treatment about 20 years ago for a version of AMD, age related macular degeneration.

[00:05:50]Um which was where a lot of blood vessels begin to sprout. And so we had it's known as wet AMD. And so we have um have had treatment from cancer research being applied there and that has helped uh attenuate some of that acute um disease and and help preserve vision.

[00:06:16]we don't have such a a a a difficulty um in in we still have a lot of difficulty in finding treatments uh for other versions of AMD because it's a very complex disease and the question is why is that why is it that although we have been studying this disease for 20 to 30 years although science has been really uh making a lot of progress. Why is it that we still can't quite discern what's the best treatment? And we believe that fundamentally it's because it's complex and requires a complex research approach.

[00:07:04]A lot of the ways that uh scientists have been approaching research is at a singlestep focus. We want to show and I'll I'll really describe that later uh how we are making different approaches all combined into one so that we really get as much information and a comprehensive overview a comprehensive map of this whole disease.

[00:07:32]Let's have a look at the the the subject territory as it were. Uh what what do we need to map?

[00:07:40]So this is the eye. Um and in here we have it uh from the side almost if we look at uh look at the eye globe from the side. uh and I'll describe some of the components here where towards the back we have the retina which is the part that is responsible for capturing light and it's all over the back of the the globe and this is the the part that really responsible for capturing uh and giving us vision. Now the retina consists of small parts called cells and each type of cell has an important role to play. For instance uh there's a cell type known as photo receptors which receive packages of light called photons. Hence why they're called photo receptors. And so as soon as light gets detected these photo receptors send off an electrical signal uh for the brain to decode. And so each of these photo receptors uh have a specific job where they can detect different colors, blue, red or green or anything in between or help us see in the dark.

[00:08:55]We have in just one eye around 126 million of these photo receptors and that's not counting the millions of other cells that are are helping. If our brain were to try and decode each of these signals, that would be really really difficult. That would be a lot of work to uh and a lot of noise. So, some of the hard work is already done at the retina. There are many supporting cells such as neuronal cells that kind of bundle in the signal. There's other ones that help sharpen contrast, that help us see in dim light, and help organize the signals before they're sent to the brain.

[00:09:42]Now, remember, there are 126 million of these photo receptors, and that's not again counting all the other ones. Each of these cells need energy to function, to continuously send off electrical signals, uh is really energy intensive.

[00:10:00]And that's done by uh by blood vessels that are hidden or kind of underneath the retina but also within the retina which provides the nutrients and the sugars required to keep everything working.

[00:10:16]So as I mentioned this, we're talking about millions of photo receptors, millions of vessels precisely orientated where they need to be to provide that energy for those electrical signals.

[00:10:28]We've got millions of cells involved in packaging and helping to to to modulate and and and allow us to see much better.

[00:10:39]And all of those are next to each other in a very specific formation in very specific structures.

[00:10:48]The eye is genuinely most of the one of the most complex organs in the body. And that's not even mentioning the macula, which is even more complex because this is the part that allows us to have visual acuity. This is the part that allows us to read or drive, allows us to have that clarity in the center of our eyes wherever we look. And so it does it by packaging even more of these photo receptors right in the very center. And so it's structured in such a way where even blood vessels are kind of forming a ring around it. so that it's not in no way so that we can see everything clearly.

[00:11:27]And so there are a lot of moving parts that essentially need to be organized in a very particular confirmation configuration. So the body and the eye has structures and scaffolding in place to ensure that every system is working.

[00:11:46]When a building for instance if I use a metaphor uh when a building is new the support systems are strong and efficient but as we age these loadbearing beams are gradually deteriorating. It's sort of in the name age related macular degeneration. As we get older you know age is the biggest risk factor for a lot of these diseases. Sort of almost [snorts] the same way as we get wrinkles as we get older. And we suspect that a similar sort of thing is happening.

[00:12:19]You know, over decades, wear and tear is is accumulated. Repairs aren't as efficient. You know, waste is not removed as quickly. And so, particularly if there are some prior factors, you know, this can really contribute to the formation of the disease such as age- related macular degeneration.

[00:12:39]Now some scientists theorize that it may be to do with the immune cells immune system becoming less efficient or our blood vessels and energy not being effectively delivered and these really hungry these energy efficient cells photo receptors just not quite getting what they need or creating too much waste product around.

[00:13:03]We know, for instance, that certain people have genetic predispositions or potentially lifestyle choices that may contribute to the disease. But here's the catch. Just because someone is aging doesn't mean they have age- related macular degeneration. Just because someone has particular genes doesn't mean that they may have AMD.

[00:13:27]Likewise, if they have certain lifestyle choices, it doesn't necessarily mean that they will either. It's for every person, it's different. It's a mix and mash of so many different um factors that all combine together. And just because you have one of them doesn't mean that you will absolutely have uh a AMD. It's not as simple as for instance um we know that smoking causes lung cancer. It's a pretty clear cut cause and effect. It's not so clear cut in AMD. And ultimately what this means is that we find that AMD is a multiffactorial disease. It requires a lot of different factors, a lot of different lifestyles and for every person it's just different. And that makes it really hard to to investigate.

[00:14:21]Now, why is this really hard for scientists to look into? Fundamentally, the way the simplest way to do science is to pick out one of those reasons and let's find out everything that we can about it. We take one component at a time and see if we change this, make this better, make this worse, does that change everything?

[00:14:45]this if you do this for every single cell type or every single component or structure first of all takes a long time but secondly it doesn't tell the full story as I said AMD is a multiffactorial disease and so the reality is that in in in a retina that's so structured and so um specialized and so complex with all these different factors affecting it the geography of the tissue and how it's all placed in relation to each other is exceptionally important.

[00:15:23]This is what we've been doing for many many years. you know, we have these maps, these old maps really, um, which is what the current gold standard has been, where we're able to look and discern the microscopic anatomy, the geography of the tissues, um, using special dyes. In in a way, it's uh, it's kind of like highlighting specific cells and specific structures and then using a microscope to view them. So in here for instance as an example on on the on the screen as I'll describe it we have we can use a blue color or slightly purplish color to look at all the cells and all the different components there and we can use the pink color to look at the structures. So, we're able to say there's some neuronal cells, there's some bipolar cells, kind of cells in between that are helping uh and there's photo receptors at the very bottom of of uh of our retina.

[00:16:28]Now, this method really allows us to see the geography of samples. And I'm actually only telling you which of these cells are which because I've done this for the past 3 years. [laughter] However, even with my experience, I wouldn't be able to tell you. And actually, no one could based these two colors.

[00:16:50]What specifically are these cells? We can guess that they're bipolar cells or neuronal cells, but what's actually happening to them? You know, are they physically there, but functionally they're not working anymore? We wouldn't really be able to tell.

[00:17:08]The issue with these traditional methods which use two colors at a time is that it can only highlight a handful of features in one go.

[00:17:20]This is where our project comes in. I'm going to talk about a technique called IBEX. Now, it's a mouthful to pronounce um for what what it stands for. It's iterative bleaching extends multipplexicity. Uh I never I never like saying it, so I always say IBEX. Uh but let me let me just describe what what it does. I mentioned previously that we use dyes and colors earlier to highlight cells and structures. Let's take the same idea but let's use multiple colors at the same time. Really extend that. So instead of just using purple and pink, let's use ultraviolet, blue, green, red, yellow, a whole array of it that can be detected by a microscope. And this already allows us to see up to seven colors at one time on one tissue.

[00:18:15]Now, here's the really cool thing about IBMAX. as we have some of these colors on the tissue. Um, we can take an image, go to the microscope, take that that photo, and we still have the tissue there. So, what if we remove these colors either by bleaching it, that's why the the bleaching part of IBEX comes in, or by removing the colors, allowing us to go for another round. So we can go seven colors image remove seven more colors and we can do so in a cycle. That's what iterative means. It's a cycle.

[00:19:00]And so when we image these these these tissues this this retina several times we don't get what the rest of the world does which is two at best three colors.

[00:19:16]We can get up to 40 40 unique markers, 40 unique different colors and structures that really allows us to get uh discern what's happening uh within the sample.

[00:19:35]Let me use a metaphor. Let's say we're trying to map a city. If we only have two colors, I could tell you where the hospital and where the train station is, but we miss a lot of details in between.

[00:19:49]Our job with this technique that we call ibecks is to place dozens of landmarks onto the same map at the same time.

[00:20:01]Now, you might ask the question, what's the benefit of this? This is really colorful, really bright. But why is this useful?

[00:20:10]Remember how earlier I mentioned that we've got scientists considering whether it's the immune cells, whether it's the blood vessels.

[00:20:20]They have to choose and investigate it one component at a time.

[00:20:26]We don't have to do that here. I've selected and and instead of choosing whether I look at one factor number one factor number two I encompass as much of that to visualize it and see it all at the same time.

[00:20:44]This techniques allows us to take a multiffactorial approach looking at immune cells, blood vessels and everything else in between for a multiffactorial disease.

[00:20:57]Now I talked about the geography and and how important it is to to really do that.

[00:21:04]This is one of those cutting edge technologies that we have adopted recently that the rest of the world is beginning to apply in cancer research which is usually the part that's really well funded. And here we are already applying this to uh to AMD to healthy retinas and being able to grab these maps and provide them for research scientists to use so that if they investigating immune cells and how that affects the uh the disease, they also can see at the same time there's this whole other field that they might not have had the time to investigate.

[00:21:47]and hear it all in one kind of map to be able to look at it all at the same time.

[00:21:54]What about clinical understanding? What about clinical treatments? Now, this is a future task, but I think it's really really feasible. You may be familiar uh and I am assuming here but uh one of the techniques that are used by clinicians is something called OCT uh optical coherence tomography which is a form of um almost ultrasound uh that allows us to get this black and white images in the back of the eye um to see while the patient is is um you know in the hospital uh what's actually happening towards the back. And this has been a revolutionary tool for for clinical treatment and interpretations.

[00:22:37]However, to this day and still, clinicians, all they see are gray bands, gray colors that just gray lines really that that refract um just the the ultrasound, the OCT as it were. And so although it's been helpful in assuming this is most likely a a buildup of fluid, therefore you need this treatment. This is most likely damage of these kind of cells probably just because we see the bands the gray being a bit different to what it what it was like. This technique can be applied to that where if we do optical coherence tomography on post-mortem tissues and we see what these bands are and then image them with IBEX like we've done here, we'll be able to not say we think these gray bands are these, but definitively say this gray band and this deterioration is this protein or this photo receptor breaking down in this way? And I think that's that's the the huge benefit uh a future benefit of this this project that we can potentially achieve.

[00:24:01]Now, I've talked a lot about the the project uh in theory and and what we've been able to do and and stuff like that, but I'd like to pivot slightly from from that idea and actually tell you about the the journey that I went on. Um so I I started my PhD back in 2023 and so 3 years ago and immediately from the very beginning the biggest hurdle we knew we had to overcome was actually acquiring the retinas. Uh it's all nice and well to have this technique set up but if you can't image it on any tissues that's a bit difficult.

[00:24:41]One avenue that we had was the generous donations uh of eye globes uh to the NHS. So that were predominantly used for corneal transplants. Um so the front of the eye can be replaced if someone has a severe disease or traumatic injury. But the remaining part of the globe, the back of the retina, the maculas, those are those are left for research. And so none of this work that I've been able to do this would have been possible without the generosity of of tissue donors and their family. You know, that decision to to donate this has been has has an enormous impact on research and our ability to be able to understand diseases such as AMD.

[00:25:28]There is a little bit of a an issue however which is when people um who donate these eyes they pass away and and their tissues are given for for science um one of the first cells to die and it is because of that high energy use that I had mentioned before are actually photo receptors. So when we try to so we try to essentially discern you know is the disease because of the post-mortem the person passing away or is it because of of of AMD. It's a bit hard to to to grasp and so we try to get that clock stopped as quickly as possible by fixing the tissue and kind of stopping it with chemicals that prevents the degradation process. However, for a lot of these samples, these post-mortem tissues, the fixing process usually takes around takes time about 36 hours after after death, which is a little bit difficult to do research on.

[00:26:31]So, we had to get the retinas and I've had uh the absolute pre pleasure um to meet one of the leading experts um in age related macular degeneration in the United States. Um and so what we've been able to do is arrange in May 2024 for me to fly over to Iowa of all places. Uh I've never been to the US so going to Iowa as as the first experience is very unique I think. Um and so there in the lab at the University of Iowa, they have um set up a system uh because they have a university hospital nearby um to try and grasp some get some of these tissues within 4 hours of of of death, which is a huge difference between now between 36 and 4 hours.

[00:27:34]And so the other advantage is that with a leading expert uh such as with Dr. Robert Mullins who is the the the expert at the University of Iowa um they do a lot of research on AMD as well. So we've been able to foster collaboration um especially after I flew there for about a week to demonstrate what I've shown here in this presentation IBEX.

[00:27:57]Um, so we've sent off antibodies. Uh, we've shipped it off and then I shipped myself off uh to Chicago first and and flew over to to Iowa and uh yeah, throughout that week we uh done a quick IBEX experiment and some of their tissues that they've had and we've been really fortunate to to see uh some incredible work there and this hasn't this has continued. uh they've in I don't have to fly as often but they did ship tissues to us to to the UK where I've been able to um to look at some really unique samples not only healthy retinas uh but also with intermediate stage uh AMD so that with dusen and and that sort of uh stage all the way to super rare tissues with endstage uh geographic atrophy so when you have that uh deterior deterioration of the eye or even wet AMD um the whether new blood vessels uh were formed. And so really we have a whole spectrum of tissues from healthy to uh to bits in between and all the way at the end that we've been able to image and map. And so these it's around about seven unique tissues with excellent quality on top of some of these corneal transplant tissues that I was mentioning that we've been able to image with up to 40 markers. And so the way that we do this um as I'm showing here the one of the um one of the healthy maculas with all the colors that I could possibly put on it um where we're able to see the structures uh of the uh of the healthy macula with the nerves at the top, the photo receptors towards the bottom, the vascule at the very very bottom uh and compare it to uh geographic atrophy where this structure completely deteriorates and these colors and and and and markers are are are disappearing.

[00:30:04]And so in short, if I were to summarize this project, for the first time really in history, we've been able to generate highly detailed maps of these healthy and diseased tissues and a whole kind of spectrum in between. Uh that allows us to view these blood vessels, uh the support systems, the immune cells, um the the photo receptors, uh that all within the same tissues that are going to be openly available for researchers and for clinicians to use um for whatever research they want to do down the line. And so I think this these maps uh and I really hope that they will become a resource as a foundation block for us being able to go back a few steps and understand what is AMD, what are the multiple factors that are affecting it, not just one or two, but really kind of have a comprehensive overview of it all.

[00:31:11]So to wrap it up a little bit, um it's been a bit of a journey over the last few years and I've had a lot of opportunities to to improve as a uh as a person. Um which I wouldn't have had the chance to. Uh you know, I I've learned how to code, which I've not done at all before, just to be able to grasp some of the analysis and the data out of this as well. Um, you know, I've been able to learn microscopy and and how to do all that. Um, and I've traveled to the US and met some incredible people at conferences and uh and talks and everything. Uh, even those organized uh by the macular society uh that I've been to uh and been part of a a workshop uh to really help get a clinical and and and research uh improvements for for for patients. Um, so I'm I feel incredibly grateful uh for this opportunity and the generosity of all the supporters of the Mecca Society um has definitely allowed me to to contribute uh I would say a small addition but it's actually I think it's a pretty big addition uh to the field as a whole to the larger scientific effort. Um, and while there's still a lot that we don't know about AMD, uh, I do believe that a lot of these studies like this will really help build up the foundations the way that they should be, uh, for the discoveries and treatments of the future. Uh, thank you. This is our lab over here. Um, so on behalf of of the Chew Lab, uh, thank you very much for listening and I'd be delighted to answer any questions uh, from the chat. Thank you so much, Cuba.

[00:33:00]Really fascinating talk and just incredible to see those images and the level of detail you've been able to generate. I mean, really truly extraordinary. So, thank you. When we were talking just before the webinar started, you were telling me about your enthusiasm for your research and and it really kind of came through in your talk, that passion you have, and I think you need that passion, don't you, to do a three years.

[00:33:23]>> Absolutely. [laughter] But it's but it's been lovely to see. um you you sort of said thank you to to our supporters towards the end there. So, thank you for that. And actually, one of the questions we've had uh was someone asking how they can donate to this fantastic research.

[00:33:39]And I'll sort of give a first answer to that. I know my colleague has placed a message on the chat. But if you do ever want to support our work, you can go to our website, which is macularocciety.org, and there's a big donate button towards the top. Or if you prefer, you can call our wonderful support care team on 01264-350-551.

[00:34:01]That's 0126435051.

[00:34:06]And there every working day, Monday to Friday, 9 to5, and we'll be very happy to take your um your donations. So, thank you. I mean, we we did wonder if if the question was about financial donations, which we're obviously happy to donate, or tissue donations, and you sort of touched on, I guess, the complexities of tissue donations. I don't know if you if there's anything you could answer in terms of people who wanted to donate tissue in the UK towards research and what options there there are for that.

[00:34:35]>> Yeah, absolutely. So, um, as I mentioned, the NHSBT is the the most, um, set up and the most robust system at the moment where where you donate, uh, a lot of the research there. Um, it's I'm not entirely sure if Morfield's eye hospital might have another system as well in place. Um I have heard a few things here and there as well that I've tried to uh to to work on but it's it's uh it is surprising that being next to an eye hospital. I'm at the Institute of Opthalmology at UCL and right over there is the is Morfield's eye hospital. Uh right behind the window uh and you'd think it'd be a lot easier to acquire tissue uh and and have these these donated samples. Um, I am willing to to try and find out from clinicians. I think that's probably the better uh the better answer on on what the the best way to do, but NHSBT is is the one that is the most robust and and for >> Okay. So, maybe it's something for people to talk to their clinicians about if that if that's an option they're interested in exploring. But um but if it is a financial donation, we are we are very grateful for those and we're we're happy to say that's a much simpler process.

[00:35:54]>> Um just turning to the other more uh more scientific questions, what's what's next for this research and what would your dream be for what it means for AMD?

[00:36:06]>> Yeah, great question. So I touched a little bit on that on future directions which is um that we would love to apply this to these OCT images these uh that what clinic what we see clinically uh in vivo uh and be able to map a lot of this the these sections uh these images together uh so that people can know a little bit more on what each of these bands actually means rather than kind of guess. But there is something that I have actually done um and already started working on which is we've been looking at a lot of these samples from side on in these thin slices that are actually thinner than human hair. Um and I've been working to try and look at it all in 3D. And that's something else that uh that that we've been able to try and apply. uh and really get a sense of how all of this interacts not just uh from side on perspective but really from sort of uh onfast as it's called. So when we're looking at it directly where we see all the vascule and all the kind of 3D structures and if we can get that with OCT images that will be uh pretty groundbreaking I think so I think that's that's uh that's the future and and the dream I think.

[00:37:32]>> Fantastic. and and someone asked what sort of more specifically what the um clinical implication is for patients. Is this about improving imaging or is this about leading for therapies? What do you see as the the root there?

[00:37:47]>> So ultimately it's not about determining cures or treatments just yet. It's about having a foundation for people to uh do further research on. Uh in short, like I mentioned, we tend to research and and do uh research almost one at a time. I'm hoping that by having this kind of map and building block and sorry that people would be able to um researchers would be able to look at uh whatever they're investigating a little bit more holistically and therefore see better treatments from that. Um otherwise they might be missing perspectives that they haven't really considered before. Um so it is a uh it is a bit removed from treatment. uh at the moment. Um but I I'm hoping that it's it can be a good stepping stone.

[00:38:46]>> I guess if we think back, it's like sort of trying to do science before the adventure of the microscope. You you couldn't really see what on earth was going on. And the person who invented the microscope, whoever that was, obviously has has transformed everything. And >> yeah, >> um these kind of new technologies can can give us similar perspectives.

[00:39:03]>> Exactly.

[00:39:04]>> Fascinating. And um so I'm just going through the questions. I'm trying to sort of group them in a similar way. Um, does the number of photo receptors diminish as we age and if so does this affect AMD?

[00:39:22]>> It's a very good question. Um, within AMD, yes. Uh, the number of photo receptors.

[00:39:31]So, the answer is yes, but not as significantly as we we think. Um, a lot of the the cells as we age are there.

[00:39:42]Um, and they they seem they what we're born with is kind of what we get towards the end. There's no there's no new cells being made. That's one of the the parts with with the retina that it's so um so structurally dense and so specific but there's very few kind of repair mechanisms of new cells like let's say in in you know scarring for instance of of of the skin if you cut your skin then you get that so in AMD yes photo receptors uh they die off and this is the question that we're ultimately trying to answer. Why? Is it because of these blood vessels, the energy not being there? Is it because of waste products not being removed? Is it because of the immune system? You know, there's a lot of theories going on and it's it's all about um really being able to kind of view it all in a uh all at the same time to to try and get that understanding.

[00:40:42]>> Fascinating. Um, and I guess sort of linked to that, and I appreciate this is not not kind of core to your research, but what determines how fast AMD progresses?

[00:40:55]>> That's getting very clinical. Um, and it's it's Yeah. So, >> that's fair enough.

[00:41:03]>> Yeah. So, >> the question the question is is very very good and the qu the answer is it depends. Um, like I said, it's multiffactorial and for every person it's different. Diet, previous uh experiences, stresses, uh, you know, whether um, you know, you've been smoking or not, genetic factors, it's all very variable. Um, it's not a simple answer, unfortunately.

[00:41:28]>> Yeah. So, there are a few sort of very clinical questions and and as as Cooper isn't a clinician, we'll we'll screen those out if that's okay. Um but I'm I'm sure in a future my macro me will have the I mean we we've had lots of opthalmologists on these. So um we'll store up those questions for those sessions. Um we've had a few questions regarding myopia and is this is this research a resource that could better understand pathological myopia in future and was um myopic M andd excluded from the research or was it included?

[00:42:02]>> Uh yeah so it was excluded. It wasn't included in here. um we we weren't looking at at myopia. The good thing is is that this technique can be applied to any disease. Um for instance, I've done a lot of work on um not quite related to this uh to to macular stuff um but on uvitis uh so it's inflammation of the eye as well trying to really have all these immune cells and seeing what they're doing. um you can do it for um any technique really. This is one of the good things that this IBEX technique can be applied so long as you have tissue to any anything. Um and it's it's much more accessible to to research and scientists because it's it's made by us in house.

[00:42:56]It's not a company that that says you got to use this this platform, this tool. So, it's it's a lot more affordable and and a lot easier to to set up.

[00:43:07]>> Fantastic. Um, I'm just thinking that might be the end of the the questions we've got if we take out some of the more clinical ones. But, um, but thank you so much. As I say, really really interesting talk and and yeah, fascinating to see this tool and hopefully we'll see it really widely used and it will accelerate research across all forms of macular disease. So, thank you again.

[00:43:33]>> Thank you. Um, next month our my macro and me webinar will be taking place on the 18th of August at the usual time of 700 p.m. We'll be hearing from consultant ofologist Martin McGibbon, sorry, Muk Gibbon, who has been working to better understand how patients experience treatment for wet AMD at different clinics across the UK in order to improve care by placing patients voices at the center of care. Their project aims to understand and improve treatment experiences, reduce anxiety, and improve treatment adherence and outcomes. Martin will also discuss the development of a new patient reported experience measure for AMD, which is a questionnaire designed to capture what matters most to people receiving treatment. He'll explain how the researchers inform the questionnaire and how it'll be tested in the next phase of the project. That sounds absolutely fascinating. I won't be hosting it myself as I'm going to be on annual leave, but I'll certainly be watching it back because it sounds really very interesting. Um, what I also want to do is mention our hope for the future conference which takes place every September and it's taking place this Saturday the 12th of September. So, it's an online conference with a number of different sessions looking at every aspect of um, macular disease. It's free to attend. You'll just need to register on our website. And as always, my colleague Em is ahead of me and has included a link in the chat. Um, if you want to register uh and I'm sure it's very visible on our website as well. So, please do. It's very much like our my webinar, but it's kind of bigger and better with lots of different speakers.

[00:45:14]So, please do join us for that. So, um once again, I'll just say a huge thank you to Cuba and uh congratulations on your research. only got a couple of months left, so no doubt be very busy um over those coming months, but good luck with the final stages of your PhD. Uh thank you for joining us tonight. Thank you to everyone who's joined us to listen in on a really interesting talk and and a particular thanks to all of those who supported us and therefore enabled uh Cub to complete this work. So thank you. Have a lovely evening everyone and uh we'll see you next month. Take care. Bye.

[00:45:46]>> Thank you very much. Bye.