ARVO 2024: Mapping the melanocortin receptors in the human eye

At this year's ARVO meeting, Paul Kayne, PhD, gave insight on his paper titled "Mapping the melanocortin receptors in the human eye."

Video Transcript:

Editor's note: The below transcript has been lightly edited for clarity.

Paul Kayne, PhD:

Hello, my name is Paul Kayne, I am the Vice President for Biological Sciences at Palatin. We work in the melanocortin system. And that's in fact, what our poster was about, is looking at the melanocortin system in the ocular space. To understand the melanocortin system, you need to know that it's an endogenous system that the body normally uses to maintain homeostasis. And what that means is, at least in the realms of inflammation, is that when you have an inflammatory event in a normal, healthy person, the inflammation needs to clear. And what happens is that the melanocortin system is called, it tells the immune system to finish up and to start being pro-resolution. It tells the tissue cells that called for the inflammatory response that, "Things are now taken care of, please turn off your stress signals, return your seats to the upright and locked position, and you'll be ready to go and everything will be back to normal." That's the best-case scenario when you're healthy. Of course, in disease, things go wrong. So what we do is we take agonists of the melanocortin system, and we encourage it, when the disease isn't normally being handled and returning to homeostasis. The challenge in this is understanding what we want to deliver it to, where the receptors are. And so that's what this poster was about, was looking at the melanocortin 1 receptor, which is largely responsible for this whole return to homeostasis. But also we looked at at the melanocortin 3, 4 and 5 receptors, which in the ocular space, seem to play an important role, particularly 5. So we did that by creating special reagents to give us very high sensitivity, to look in human donor tissue, where we dissected out the various components of the eye, and then measured the messenger RNA of the different melanocortin receptors, 1, 3, 4 and 5. And we could show that we have...the messenger RNA is present, certainly in the cornea, the retinoid, the choroid, and a few other tissues. And you'll need to see the poster to get all the details, of course. We also wanted to look at the protein itself. RNA doesn't tell you the entire story. And so we developed a an extremely high-specificity, monoclonal antibody that can detect melanocortin receptor 1. We did this because commercial reagents weren't either specific enough or selective enough or potent enough to let us visualize. And so using this, we are able to confirm a number of the results we saw with the melanocortin 1 receptor mRNA. We see the protein present in some of the same places. Not all of them, though, as the detection isn't as sensitive. So with this understanding of where the receptors are expressed, we're now able to have a better idea of how we're impacting the eye and seeing how we're affecting the homeostasis of the eye in disease.