Podcasts about kir4

Hello, and welcome to Episode Forty-Six of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features the first part of a two-part interview with Dr. Hans Lassmann, who discusses biomarkers in multiple sclerosis. But first, here are some of the new items in the MS Discovery Forum.   According to our curated list of the latest scientific articles related to MS, 61 such articles were published last week. To see the list, go to msdiscovery.org and click on Papers. We selected two of those papers as Editors’ Picks. One, on the prevalence of pain in MS, found that around two-thirds of MS patients experience pain, and this symptom is associated with disability, depression, and especially anxiety. The other editor’s pick is a study of a toxin produced by Clostridium perfringens, a common bacterium often found in the gut that produces an MS-like disease in sheep. This epsilon toxin selectively kills oligodendrocytes while preserving all other neural elements.   Our Drug-Development Pipeline includes continually updated information on 44 investigational agents for MS. During the past week we added 2 new trials and 5 other pieces of information. The drugs with important additions are dalfampridine, dimethyl fumarate, and fingolimod. To find information on all 44 compounds, visit msdiscovery.org and click first on Research Resources and then on Drug-Development Pipeline   [transition music]   Now to the interview. Dr. Hans Lassmann of the Medical University of Vienna in Austria, is one of the most prolific and highly respected MS researchers in the world. In this first part of a two part interview, Dr. Lassmann discusses biomarkers in MS and related conditions such as neuromyelitis optica and how the two conditions may differ important for therapy.   Interviewer – Dan Keller Let’s talk about new markers in MS or differentiating conditions from MS. What’s coming along, and what do we know now?   Interviewee – Hans Lassmann Well, there has been a very important development during the last years. And this was the technical development of assays which can really identify pathogenic autoantibodies which can modify the inflammatory process in the central nervous system. The major trick behind was that these assays are, in essence, based on cells which are transfected with the respective antigen, and so they express the respective antigen on the surface of the cell. And one can now identify those autoantibodies which really bind to the surface of the cell and are pathogenic, in comparison to those antibodies which recognize epitopes, for instance, within the cells, which cannot be reached by the antibodies in the in vivo situation, and which, therefore, are not pathogenic.   MSDF Can you give me some examples of these kinds of antibodies?   Dr. Lassmann So the first antibody which was the antibody against aquaporin 4, which has been shown to be associated with neuromyelitis optica, at least with a large fraction of patients with neuromyelitis optica. And this antibody then was very well characterized, and it turned out that it is directed against aquaporin 4, which is a water channel in astrocytes. And when patients have these antibodies on the background of an inflammatory disease in the central nervous system, these antibodies can reach their astrocytic targets and destroy the astrocytes, which then leads to secondary demyelination and neurodegeneration.   Having these antibodies, it was then possible to define the clinical spectrum of the disease, and it turned out that it is very strictly associated with neuromyelitis optica, but that the spectrum of the disease is broader than only affecting the spinal cord and the optic nerve. So these patients actually have also lesions in other regions of the brain. But they are still different from those lesions which you see multiple sclerosis.   It was then also possible to define the clinical spectrum of the disease. And, again, differences to multiple sclerosis became very clear. And, finally, it was also possible to then look in these patients with these aquaporin 4 antibodies how they respond to the current treatment strategies which have been established for multiple sclerosis. And it turned out that several of the key therapies for multiple sclerosis, including interferons but also natalizumab or fingolimod, can actually make the disease worse in patients with neuromyelitis optica.   So that was the first example that a disease which has originally been defined as a disease in the spectrum of multiple sclerosis has emerged as a separate and distinguishable disease which requires also different treatment in the patients.   MSDF It seems like neuromyelitis optica has components of autoimmune disease. So why do these compounds that work in MS potentially make the condition worse in NMO?   Dr. Lassmann This is currently not yet clear. One possibility is that the action of pathogenic antibodies makes the difference. The immune mechanisms are certainly different in a purely T-cell mediated disease, in comparison to disease which is mediated by a combination of T-cells and antibodies. And that could possibly explain why differences are seen.   There is another possibility is that some of these drugs actually stimulate the B-cell response or increase the B-cell response in the peripheral blood, and with that possibly also the antibody response. So, in that case, the T-cell mediated inflammation would be suppressed, but the antibody-mediated effects would be enhanced. And that could certainly also play a role. But these are, at the present moment, not proven.   MSDF But even in MS there’s evidence for B-cell trafficking and B-cell participation, but it seems to be less important or am I off base?   Dr. Lassmann No, this is a very interesting question. There is clearly a B-cell component in multiple sclerosis, and it has also been shown that depleting B-cells, for instance, with an antibody against CD20 can actually have a very good therapeutic effect in multiple sclerosis. However, we have to keep in mind that B-cells not only produce antibodies, but they have also other immunological functions. So one function, for instance, is that they help the T-cells, for instance, by very efficient antigen presentation. So by eliminating B-cells, you get also a decrease of the T-cell response. But this is not only one possibility. There are other possibilities that B-lymphocytes actually can also produce cytokines – proinflammatory cytokines – which may directly act on the tissue and damage the tissue independent from antibodies.   MSDF Getting back to NMO, if someone tests negative for antibody, but has clinical signs, does that rule out NMO or are you just not detecting antibodies or is it always required or not?   Dr. Lassmann So it rules out an aquaporin 4 antibody associated form of NMO, but a fraction of NMO patients – it’s around between 10 and 20% – which have a clinical presentation of NMO, but have no antibodies against aquaporin 4. There is currently very much effort to define what is the mechanism in these patients. And it turned out that a fraction of these aquaporin 4 antibody-negative NMO patients actually have antibodies against myelin oligodendrocyte glycoprotein.   And this leads, actually now, to a second type of disease which can be separated from multiple sclerosis. These are patients with high titers of pathogenic antibodies against myelin oligodendrocyte glycoprotein. Now, again, these patients, when you look at them at pathology, you would clearly define the disease as multiple sclerosis because they have inflammation, and they have very selective primary demyelination. And this is different from what you see in NMO where the astrocyte pathology is the earliest event. But in those patients with the MOG antibodies, its demyelination sort of hallmark, actually, of multiple sclerosis…of the disease process in multiple sclerosis.   However, when you now analyze these patients with mock antibodies, clinically you see that the clinical presentation is different from the classical presentation of multiple sclerosis patients. These antibodies are, for instance, frequent in children with inflammatory demyelinating disease of a spectrum of acute disseminated encephalomyelitis or relapsing disseminated encephalomyelitis or even patients with a disease similar to relapsing, remitting multiple sclerosis. This is in children.   In adults, you find these antibodies in a fraction of NMO patients. But there are also other patients who have a disease which is more similar to what is seen in multiple sclerosis, with the exception that they have relatively large and aggressive lesions, and also that they have, relatively frequently, lesions in the brain stem such as, for instance, the pons or the medulla oblongata. And, again, it seems to be that here a new disease entity appears which can be separated from multiple sclerosis.   Regarding therapy of these patients, we don’t have yet the data which we need to have. It can be speculated that the therapeutic response may possibly be more similar to those patients with NMO in comparison to the classical MS patients, but to know that we would have to have much larger cohorts of patients who have been treated with the different regimes.   MSDF Do some of these do worse on the typical MS treatments such as natalizumab or fingolimod?   Dr. Lassmann These data currently are not yet existing. It’s also because, due to these possible problems related to NMO, generally now, patients with mock-antibody-associated diseases are more likely to be treated with global immunosuppression or with rituximab, so the anti-CD20 antibody. And clinicians are very reluctant to use these therapies which have been shown to make disease worse in NMO in these mock patients. So we don’t have the data, currently.   MSDF Are there separate etiologies, does it look like here, the MOG versus classical MS?   Dr. Lassmann This comes to the important question about the etiology of MS in general. We have to admit that we don’t know what is the real etiology of multiple sclerosis. It is thought to be an autoimmune disease, but this is not finally proven. It may also be associated with infections – Epstein-Barr virus infection is, for instance, one possible example. And there are certainly other theories also, which discuss completely different mechanisms of disease pathogenesis in multiple sclerosis. It is clearly that all these diseases, including NMO, mock antibody associated disease, and MS are chronic inflammatory diseases. But what drives the inflammation is currently not yet known.   MSDF Is it possible there’s an initial insult to oligodendrocytes which then sort of precipitate a chain reaction cascade?   Dr. Lassmann This is also one of the theories which is put forward, but one has to say that with a bit caution, because there are experimental models where you can actually destroy oligodendrocytes in the central nervous system which do not lead to an autoimmune disease which is somehow related or similar to multiple sclerosis.   MSDF Anything interesting or important to add on the subject, in this context?   Dr. Lassmann I think what is now of interesting new research line is to search for additional autoantibodies in the population of multiple sclerosis patients. There are indications from pathology that there are certainly more patients who may have pathogenic autoantibodies, in comparison to those patients which now can be identified as NMO or mock-autoantibody-associated disease. There is a relatively recent study suggesting that another channel, a potassium channel on oligodendrocytes and astrocytes, the KIR4.1 channel, may also be a target for pathogenic autoantibodies in multiple sclerosis. Here, however, we are still in the very early stage because the test systems are not yet fully reproducible. And we will see in the future whether this antibody association with the KIR4.1 antibody really holds true in MS patients. And if that’s the case, what patients are they and whether they differ in any way in their clinical presentation or also response to therapy.   MSDF Is there a way to survey patients and essentially see what commonalities they have in antibody reactivity, and zero in on it that way, looking at a wide array of antibodies in various patients and seeing if they have reactivities in common?   Dr. Lassmann I think this is valid as a second step. But there is another alternative strategy which is now very well established also for other diseases, including paraneoplastic diseases or other autoimmune diseases. In that case, one can actually take the sera of the patients, and there are now new technologies developed where you can put these sera, for instance, on brain sections – normal brain sections – of either humans or animals and test whether they bind to specific structures.   This has been tried for nearly 30 years now, but only recently, new technologies became available which make that in a much more specific way. And this has been very successful in identifying new diseases which are associated with antibodies against a variety of neurotransmitter receptors or ion channels. So they certainly, in general, have not the spectrum of multiple sclerosis. They may have epilepsy. They may have psychosis. They may have motor neuron diseases, other things. But, on the other hand, the same technique can also be used to identify in multiple sclerosis patients whether some of them have actually antibodies which bind to brain tissue. And when that is established, one can actually then isolate the specific protein with the antibodies out of the brain tissue, and then, with modern molecular biology technology, can identify the antigen.   This is a strategy which has very nicely and very successfully shown for other diseases. And this was also, in principle, the strategy how people found evidence for these, for instance, KIR4.1 antibodies and also for the NMO antibodies.   MSDF Finally, do you envision being able to develop specific treatments if you find out specific autoantibodies or causes of some of these conditions?   Dr. Lassmann It may very well be. I think there are two dimensions on that. The one dimension is that such patients have pathogenic autoantibodies, and that certainly will have implications for therapy. That means that you will try to block the pathogenic action of the antibodies in general. In that case, it doesn’t make a difference whether the antibody is now directed against a neuron or against an astrocyte or against an oligodendrocyte. And this is a strategy which is actually now already approached in many different conditions, and neuromyelitis optica certainly is a disease where this is relatively advanced in this respect.   Now, the other possibility would be to try to find therapies which are then counteracting specifically the destruction of the particular cells which contain the antigen. So it can very well be that, for instance, an antibody against a neurotransmitter receptor will have a different implication on neuronal function, in comparison to an antibody against an astrocyte or an oligodendrocyte. Here, if these are just blocking antibodies and not antibodies which destroy the tissue, one can actually then try also symptomatic therapies with interfering with these channels directly.   MSDF Is there any thought towards trying to induce tolerance or clonal deletion of the pathogenic clones?   Dr. Lassmann This is obviously the dream of immunologists, and it would be extremely attractive. And it works extremely well in inbred mouse models with a very well-defined disease induction process. The strategy is very dangerous in a genetically heterogeneous population and also in a disease process which may be induced by different mechanisms. So, in that case, the big danger is that this tolerizing strategy in certain patients, for instance, with a certain histocompatibility genetics, actually is counterproductive and increases the immune response. And this is actually a problem which is very, very difficult to solve, in the aim of translating this mouse data into humans.   [transition music]   Thank you for listening to Episode Forty-six of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]    

[intro music]  Host – Dan Keller   Hello, and welcome to Episode Four of Multiple Sclerosis Discovery, the Podcast of the MS Discovery Forum. I’m your host, Dan Keller.  This week’s Podcast features an interview with Dr. Michael Racke about the potassium channel Kir4.1 and its potential role in MS. But to begin, here’s a brief summary of some of the topics we’ve been covering on the MS Discovery Forum at msdiscovery.org.    Researchers at the University of California San Francisco have developed a new remyelination assay that allows high through-put drug screening. The assay takes advantage of oligodendrocyte’s tendency to wrap myelin around anything axon-shaped, such as plastic fibers and microscopic glass pillars. The assay has already identified several FDA-approved drugs as candidates for remyelination therapies, including an over-the-counter antihistamine now in phase II clinical trials.   In another article, we report on a new study that sheds light on the ameliorating effect of ultraviolet rays on inflammation and disease progression in mouse models of MS. In the study, MS patients sat in a therapeutic UV chamber for five sessions a week for six weeks. Even after one session, the patients had an increase in dendritic cells and regulatory T-cells. In follow-up studies with EAE mice, the researchers uncovered a possible mechanism by which these regulatory T-cells migrate to the central nervous system.   In addition to covering the latest in MS research, the MS Discovery Forum also curates news stories from around the web in our twice-weekly Research Roundup. Last week we wrote about the findings in phase III trials of daclizumab, a legal dispute between drug companies Acorda and Actavis, and a new collection of immunology papers from the journal PLOS. We also posted some social media advice as well as the amusing hashtag #yomanuscipt. Our favorite tweet: Yomanuscript is so bad the null hypothesis rejected it. Check out Research Roundup under the news brief section in the News and Future Directions tab on our website.   [transition music]   Now to the interview. Dr. Michael Racke is the Chair of the Department of Neurology at the medical school at Ohio State University. He’s here to discuss the latest findings of the potassium channel known as Kir4.1 and its implications for MS. MS Discovery’s Executive Editor, Bob Finn, spoke with Dr. Racke.    MSDF Dr. Racke, welcome. Dr. Racke Thanks.  MSDF So what is Kir4.1? Dr. Racke   So Kir4.1 is a what’s called a potassium inward rectifying channel that’s expressed on the end-feed of astrocytes and also on oligodendrocytes. And so it’s important for trying to adjust the right concentration of potassium in and outside of a cell.  MSDF   And what is its relationship to MS? Dr. Racke   Well, there’s been a lot of interest recently. There was a paper published in the New England Journal now almost a year and a half ago, I believe, from Bernhard Hemmer’s group that showed that about 50% of MS patients have antibodies directed against this potassium channel, Kir4.1. MSDF   And is that a lot more than people without MS? Dr. Racke   Right. So when they looked at healthy individuals or looked at patients with not just neuroimmunologic diseases but also other non-inflammatory diseases, the number of antibodies directed against it was very low, on the order of magnitude of like 3%.  MSDF   So what does this mean for our research in MS?  Dr. Racke   You know, for a long time people have been interested in what are the potential targets, and this would represent a little bit different target than the typical myelin proteins that one has thought of as being targets in MS. It’s also kind of interesting because of another molecule, aquaporin 4, that is expressed in the same place in the astrocytic endfeet that’s been the antibody target for neuromyelitis optica. And so I think as we begin to see responses against some of these other molecules, it’s interesting to see whether they result in in demyelination and whether that can be a new avenue for therapeutic intervention.  MSDF   Just within the last week, another study came to a quite different conclusions regarding the prevalence of Kir4.1 autoantibodies in MS. How do you resolve the discrepancy? Dr. Racke   There was data presented yesterday to suggest that one of the differences may actually be differences in glycosylation of Kir4.1. It turns out that eukaryotes—and humans are eukaryotes obviously—glycosylate proteins, and that very often glycosylated protein looks very different to the immune system than an unglycosylated protein. And since a lot of these studies take an unusual cell type and then try to over-express to your 4.1 on its surface and then see whether an antibody recognizes it, it may not be the same type of glycosylation that’s actually seen within patients with MS. MSDF   There’s a lot of research going on now on Kir4.1. What more needs to be done in this area before Kir4.1 becomes a therapeutic target?  Dr. Racke   Right. Well, so, for example, if you look at neuromyelitis optica, that if you did plasmic change in those patients, then very often those patients are benefited. So it’s as though if I take away those antibodies the patient does be better, so those antibodies are pathogenic. When that’s been done in MS, the data, it’s sort of been, I don’t want to say controversial, but in some sense it is. And then there have been studies, for example, done from the Mayo Clinic that looked in at certain types of demyelinating events where it seemed like plasma exchange did work, then there were larger studies that were done and it didn’t seem to work. And if, in fact, it’s, say, a pa a patient population where really only one-third to half of the patients have the pathogenic antibody, then if I do that study and say I’m going to do it to everybody, it may not have enough power to suggest that there’s efficacy for everybody. But I think it gets back also to this idea of what a lot of people talk about in personalized medicine, right, and the idea may be that you would be able to identify patients that perhaps had an antibody to Kir4.1, and then perhaps they would be more amenable to therapeutic interventions that targeted antibody synthesis in the blood. MSDF   Do you think that interventions targeted at Kir4.1, would that would it work much the same way as other as existing therapies in decreasing the number of relapses in re relapsing-remitting MS? Dr. Racke   For example, if you look at things like interferon, natalizumab, the way those therapies are trying to work isn’t against the specific antigen, right. What they’re really trying to do is just interrupt the disease process. And I think the difference is going to be there have been some studies where people were trying to target the specific epitopes to either myelin basic protein – the altered peptide ligand studies were like that – and there’s studies now also where people have solubilized MHC molecule that has a myelin peptide on it. And those are specifically trying to target the immune response against a very specific antigen. Now I have to say that most of those things haven’t really worked very well, and I think part of the reason is that the human immune response is complicated enough, but by the time a person has had several attacks in MS, they probably are making an immune response against a number of myelin antigens, and so if I target just a single antigen it may not work. And that may also end up being true in in terms of Kir4.1, that it’s just going to be another thing. But, I mean, if there’s enough similarities between it and some of the things that we’ve seen with neuromyelitis optica in aquaporin 4, like I say, there the plasma exchange and targeting the B-cell response in many instances has been quite beneficial to pa patients, right. And so I think that’s going to be an important next step to not just demonstrate that it can be part of the target that happens in multiple sclerosis, but whether inhibiting that response to that target actually has therapeutic benefit.    MSDF   You just outlined one area of research on Kir4.1 that needs to go forward. What are some others? Dr. Racke The other issues have to do with trying to understand exactly the cell-type specificity in terms of glycosylation, trying to understand why is it that this particular channel is a target in MS, then are other channels also targets in MS. This sort of opens up a whole other ballgame in terms of diversity of targets that could potentially participate in MS pathogenesis. MSDF   Is there anything else you’d like to add about Kir4.1 that we haven’t already talked about? Dr. Racke   I’ve been in this field for 20 years, and realistically this has been the first new antigen that really has come up. And that’s sort of interesting in and of its own right. I think the other thing, obviously, for those people who are interested in things like molecular mimicry, this gives you another molecule to begin to look at in terms of its sequence homology with infectious agents. I mean, the people who are interested in, you know, viruses like HHV-6 and Epstein-Barr viruses, and those that they think that have an important role potentially in MS pathogenesis, how might infections with those agents affect Kir4.1 expression. That’s going to be another area that’ll be of interest to the research community in MS. MSDF   Well, Dr. Racke, thank you very much.  Dr. Racke   You’re welcome.  [transition music]   Thank you for listening to Episode Four of Multiple Sclerosis Discovery. This Podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations.    Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.    We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.    [outro music]  

Die equine rezidivierende Uveitis (ERU) stellt weltweit die häufigste Ursache für eine erworbene Blindheit bei Pferden dar. Diese spontan auftretende, autoimmun-mediierte Augenentzündung tritt in der Pferdepopulation mit einer Prävalenz von 10% auf. Die ERU ist zudem das einzige spontane Tiermodell für die autoimmune Uveitis, dessen Erforschung einen wertvollen Beitrag für die humane Uveitisforschung leistet. Ablaufende Pathogenese-assoziierte Vorgänge in der Retina, dem Zielorgan der ERU, sind bisher noch weitgehend ungeklärt, tragen jedoch zu einer fortwährenden Schädigung der retinalen Gewebearchitektur, sowie der physiologischen Funktion der Retina bei. Die Müllerzellen, die retinalen Gliazellen, sind durch ihre besonderen strukturellen und funktionellen Glia-Neuron-Interaktionen von entscheidender Bedeutung für die Aufrechterhaltung der retinalen Struktur, sowie der Physiologie. Gliose bezeichnet eine bekannte Reaktion der Müllerzellen auf nahezu alle beschriebenen pathologischen Bedingungen und hat einen fundamentalen Einfluss auf den Verlauf einer Netzhauterkrankung. Die neuroprotektive Wirksamkeit steht dabei den für die Retina schädlichen Auswirkungen der Gliose gegenüber. Das Ziel dieser Studie war die Verifizierung und nähere Charakterisierung der bei der ERU auftretenden Gliose, um die Bedeutung der Müllerzelle bei der autoimmunen Uveitis zu bemessen und somit ein besseres Verständnis der Pathogenese-assoziierten Vorgänge im Zielorgan dieser Erkrankung zu ermöglichen. Dies wurde durch die Untersuchung der Expression von Müllerzell-spezifischen Membranproteinen, welche maßgeblich an der Regulation der retinalen Ionen- und Wasserhomöostase beteiligt sind, in gesunden im Vergleich zu uveitischen Retinae erzielt. Die Regulation der retinalen Kalium- und Wasserhomöostase ist eine der wichtigsten Müllerzellfunktionen und wird durch die einwärtsgleichrichtenden Kaliumkanäle Kir2.1 und Kir4.1, sowie dem Wasserkanal Aquaporin 4 (AQP4) bewerkstelligt. Gesunde Pferderetinae zeigten im Gegensatz zu anderen Spezies ein gleichmäßiges Verteilungsmuster von Kir4.1 entlang der Müllerzelle, dessen Expression bei der ERU signifikant vermindert war. Hingegen war die Expression von Kir2.1 in uveitischen Retinae signifikant erhöht, welche auch ein verändertes Expressionsmuster für Kir2.1 von Müllerzellfortsätzen hin zu den Zellkörpern der inneren Körnerschicht aufwiesen. Diese Befunde deuten auf eine gestörte Kaliumpermeabilität der Müllerzellmembran hin, die eine Beeinträchtigung der retinalen Kaliumhomöostase, sowie weiterer Funktionen der Müllerzelle zur Folge haben könnte. AQP4 war signifikant erhöht exprimiert und zeigte eine massive Re-Lokalisation in uveitischen Retinae im Vergleich zu Kontrollen. Während gesunde Retinae eine AQP4 Expression vor allem in Stammfortsätzen der Müllerzelle aufwiesen, wurde ein kreisförmiges Expressionsmuster in der äußeren Körnerschicht von uveitischen Retinae detektiert. Dies könnte möglicherweise in Verbindung mit der Entstehung eines retinalen Ödems stehen, einer der Hauptursachen für den Verlust der Sehfähigkeit bei Uveitis. In der vorliegenden Studie wurde zudem das Verteilungsmuster eins weiteren Mitglieds der Aquaporin-Familie (AQP5) charakterisiert und erstmalig dessen Expression in der Müllerzelle beschrieben. Außerdem wurde eine signifikant verminderte Expression bei der autoimmun-mediierten Uveitis gefunden und damit erstmals eine Beteiligung dieses Membranproteins bei einer retinalen Erkrankung dokumentiert. Die in dieser Studie gewonnenen Ergebnisse deuten daraufhin, dass die Müllerzelle von entscheidender Bedeutung für die Pathogenese der ERU ist, da die auftretende Gliose schädliche Auswirkungen auf die physiologische Funktion der Retina zu haben scheint. Weitere funktionelle Untersuchungen der Müllerzelle sind zukünftig notwendig, um ein besseres Verständnis der Physiologie der Müllerzelle und ihrer Beeinträchtigung bei der ERU zu erlangen. Durch die Etablierung der ersten equinen Müllerzelllinie eqMC-7 wurde mit dieser Studie die Grundvoraussetzung für dieses Vorhaben geschaffen.