Melanie Cole, MS (Host): Welcome to UF Vet Med Voice with the University of Florida College of Veterinary Medicine. I'm your host, Melanie Cole. And joining me today is Dr. Caryn Plummer. She's a Professor of Ophthalmology and Interim Chair in the Department of Small Animal Clinical Sciences at the University of Florida College of Veterinary Medicine. She's here to highlight new treatments for equine recurrent uveitis for us today. Dr. Plummer, it's a pleasure to have you join us. I'd like you to start by telling other providers what is ERU or equine recurrent uveitis. How prevalent is it?

Caryn Plummer, DVM: Well, thank you for having me. ERU is one of the most frustrating diseases that I treat as a veterinary ophthalmologist. It is an autoimmune condition that affects horses. It is very common. Unfortunately, it affects anywhere from 8-40% of patient populations depending on genetics and geography. And it is the leading cause of worldwide in horses.

Melanie Cole, MS: Wow. And it's really interesting because not everybody knows about this and its association with human condition. So, we're going to talk about that. But what are the main complications of it? And what can happen if it's left untreated or if it becomes chronic?

Caryn Plummer, DVM: Well, it unfortunately very commonly becomes chronic. And realistically, we probably should be calling this a persistent uveitis rather than a recurrent uveitis. But essentially, what happens in this condition is that the immune system kind of gets out of whack. So, there's some sort of trigger that causes the body to react to itself as if it were foreign. So, there are ocular proteins that are associated with the maintenance of what's called the blood ocular barrier, which essentially prevents either immune processes or infectious agents or drugs that are given systemically from getting into the eye and causing damage, which could alter the clarity of the eye. So, it can change the composition of the fluid, the aqueous or the vitreous humors. It can lead to cataracts or changes in opacity in the lens. It can lead to corneal opacities, changes in clarity of the windshield. So, all of these things, the body had this sort of natural way of preventing the rest of the body or exogenous influences from affecting what normally happens in the eye to keep it happy and healthy and clear. When we have uveitis, those proteins that affect or maintain that blood ocular barrier is altered. So, we have inflammation that affects the inside of the eye, and that leads to kind of a perpetuation or a self-fulfilling prophecy of progressive local autoimmune pathology from infiltration of lymphocytes and their products, cytokines and things, that cause damage to the eye.

Melanie Cole, MS: Well, thank you for telling us about that. So, are there any treatments available as of now? And if there are, are they mostly aimed at reducing inflammation? Are they symptom-bound? Tell us a little bit about treatments available as of now.

Caryn Plummer, DVM: Yes. Most of the treatments that are available are aimed at decreasing the inflammation that's present. So, essentially, altering or decreasing the overt clinical signs that we see when we examine an inflamed eye. And the mainstay of anti-inflammatory therapy for uveitis is topical and systemic steroids and topical and systemic non-steroidal anti-inflammatories. And they work quite well to a certain extent, but they're all associated with unfortunate side effects when they're given chronically.

Melanie Cole, MS: So, it would seem, Dr. Plummer, that it can have a significant impact on horse welfare, owner wellbeing, the productivity of the equine industry due to decreased performance, financial loss, change of ownership, even euthanasia. Can you tell us about this new treatment that's being investigated at the University of Florida for equine recurrent uveitis? And tell us a little bit about the studies that you're doing.

Caryn Plummer, DVM: Yes. We at the College of Veterinary Medicine have paired with some of our colleagues in the Department of Microbiology and Cell Science at the College of Agriculture and Life Sciences and in partnership with IFIS, the Institute for Food and Agricultural Studies, here at the University of Florida. And we are investigating what's referred to as a SOCS mimetic peptide. So essentially, this is a protein that is a naturally-occurring suppressor of cytokine signaling, which is essentially the cytokines that are released and produced and recruited by the lymphocytes that are in the eye causing all the damage. They are the part of this process that is self-fulfilling. So, they recruit even more lymphocytes that cause even more damage. And this peptide, it naturally occurs throughout the body and in the eye, it kind of stops that cascade of events. So essentially, it puts a halt on things, so there's no more perpetuation or at least a decrease in perpetuation of that inflammatory process that goes on in the eye.

In preliminary studies that our collaborators have done, they have shown that this peptide when administered to animals that have experimentally-induced uveitis, which is typically rodent models, that it decreases the inflammation and kind of puts the stop on that cascade of events. It's also been used in rodent models of lupus and other systemic immune-mediated diseases, it decreases the clinical signs and the perpetuation of those disease states as well.

So when we identified our collaborators, they identified us, we decided that we would try this in a naturally-occurring model of uveitis. And the only naturally or spontaneously-occurring model of recurrent uveitis is the horse. And this is a disease that affects humans quite commonly. It's a leading cause of blindness in humans as well. And it is advantageous to study a spontaneous model because the things that kind of go into the development and the perpetuation of the disease in a spontaneous model, it's quite different than what happens in the pathogenesis of an induced model, which is typically what most therapeutic agents that are put forth to treat uveitis are tested on.

Melanie Cole, MS: It's fascinating. Such an interesting topic. And Dr. Plummer, since equine recurrent uveitis shares many characteristics, as you briefly mentioned, with a disease that occurs in humans, the autoimmune uveitis, and therapeutic options in humans are somewhat limited, this topic we're discussing today serves as the only known naturally-occurring spontaneous animal model for the disease, what you're discussing. How do you envision your research translating into care for human from veterinary medicine and vice versa? Tell us how this could change the landscape of uveitis treatment.

Caryn Plummer, DVM: Well, we're early in our study, so certainly we've had some proof of concept studies and been very encouraged by our clinical results. And right now, we're working on dose escalation and the pharmacokinetics of the protein within the eye. But once we are able to essentially establish a larger multi-center clinical trial that confirms the findings of our initial studies, this protein will be able to hopefully seek approval for use in veterinary patients, but also in humans as well. So, it is a naturally-occurring peptide that has limited capacity for untoward side effects. So, we're hopeful that this will be something that will be able to be put into use in both veterinary and human patients at some point in the future.

Melanie Cole, MS: Dr. Plummer, this is such important work that you're doing. And I hope you'll join us again and update us as things continue to advance. As we wrap up, do you have any final thoughts for other providers on what you would like them to know about this research going on?

Caryn Plummer, DVM: I don't have any particular things about this in this study in particular. However, I would like to highlight the fact that equine recurrent uveitis, moon blindness, is very common in horses. And unfortunately, it's actually under-recognized. It is, as I said, the most common cause of blindness in horses. I'd like to be able to create an awareness of ERU or moon blindness, and get it out on everyone's radar. In a horse that has tearing, has discharge, has redness, has cloudiness, getting a good, complete thorough eye exam is really important to making an early diagnosis. And the earlier the diagnosis can be made, the more steps that can be taken to mitigate the vision-threatening complications.

Melanie Cole, MS: Thank you so much, Dr. Plummer. That was such an interesting topic. And for more information about the UF College of Veterinary Medicine, please visit vetmed.ufl.edu/ufachievers. And to listen to more podcasts from our experts, you can visit vetmed.ufl.edu. And that concludes today's episode of UF Vet Med Voice, brought to you by the University of Florida College of Veterinary Medicine, advancing animal, human and environmental health. I'm Melanie Cole.