ARVO Tuesday morning - Dry Eye II and The Lacrimal Gland
Dry Eye II
This session, as I scanned down the presentation titles, looked to be, easily, the least relatable of everything I have experienced at ARVO.
And yet even here, lurking under the unintelligible, unpronounceable, impenetrable depths of lab science, are glimpses into an entire world of work that comprises all the precursors to so much that we want to know and see in our dry eye world.
For example, the technicalities of “Silk-Derived Protein-4 (SDP-4) Inhibits Nuclear Factor Kappa B (NF-κB) Inflammatory Signaling that Underlies Dry Eye Disease (DED)”, as a presentation, might not quite set your pulses racing, yet what do I read about in the dry eye Facebook groups every single day? “Doctors just keep giving us stuff to treat our symptoms. We want to get at the underlying causes!” Well, guess what. Here is where the science happens that tries to get at causes. We have no idea how many people are wrestling with these questions, really.
Or, “Anti-inflammatory properties of butyrate on the ocular surface epithelium”. Another popular theme in dry eye social media is holistic medicine, diet, and how our eyes are tied to our general health. The context for this presentation was microbial imbalance in the gut due to things like aging and antibiotic treatment, and it was about butyrate, which they believe has anti-inflammatory properties on the eye surface, but originates in the gut.
Another presentation got into dizzying depths of detail on Lifitegrast (a/k/a Xiidra), and another was about testing of a drug for Sjogrens, and two others were on yet more approaches to reducing damage to cells in the eye that contribute to dry eye.
The Lowly Lacrimal Gland
“Lacrimal gland biology in homeostasis, disease, and repair - Minisymposium”
My memory of the last scientific session I was able to attend at ARVO was that it was really fun. Perhaps it’s because I’m suffering from a bit of meibomian gland exhaustion. So much of the dry eye world talks of nothing else these days. I used to worry about patients walking into a doctor’s office and being seen and spoken to as if they were a pair of disembodied eyeballs. (We really are more than a bunch of ocular surface structures flying in formation.) These days I worry even more about patients walking into a doctor’s office and being seen and spoken to as if they were a set of disembodied meibomian glands.
So I was delighted to get to focus on the lacrimal gland. A day and a half after this session, though, I could make very little of my enthusiastic and unfortunately hand-written notes. It seemed really exciting while it was happening. I just can’t always tap my inner nerd on demand after the fact, apparently. But here are a few highlights:
THEY were loving it. That’s probably why it was so much fun to be at. They said it was the first time in 30 years that they’ve had a session devoted entirely to the lacrimal gland and they were all just thrilled that it was happening. The session was actually not very well attended but whoever wasn’t there was missing out.
Darlene Dartt from Schepens (Harvard) gave a truly wonderful overview of the lacrimal gland mechanism - from the greater context of exocrine glands to the bitty details of which cell types wear which hats to get the jobs done. I got a little lost somewhere between the neural regulatory process and the thrombospondin, but that’s to be expected.
Kazuo Tsubota (Keio University, Tokyo) presented on the science of tearing. Dr Tsubota can probably best be described as simply the world’s foremost authority on dry eye. He’s also a delightful presenter, both personally and in his over-the-top amazing 3D videographics of what’s going on in the brain. He started by discussing the inverse relationship between happiness and dry eye (= more dry eye, less happy, and the reverse).
So they asked the question, are tears different depending whether you are happy or not? And as with all tear research, it seems to start with creating “a mouse model”, i.e. simulating the thing you’re trying to test, in mice. How do you make mice happy or sad so that you can test their tears? They tried to make happy mice by giving them friends, toys and lots of room to play. Based on the video shown us, yes, I can personally attest to the fact that they sure looked awfully happy! Sad mice, sadly, were basically stuffed into tubs where they were alone and couldn’t move. Unhappy is the least of how I would describe them. But the fascinating thing that they found is that when they subjected all the mice’s tears to environmental stress (e.g. wind), the eyes of the happy and unhappy mice were affected differently by the very same environmental stress. In other words, there was a brain-mediated response… which brought them to formulate the real question driving their research: “How does happiness affect tearing?” Then we learn about how the superior salivatory nucleus (SSN) control the lacrimal glands, and their research trying to pin down which part of the brain controls the SSN.
Long story short, 170 different parts of the brain - or, as Dr Tsubota puts it, “A whole lot of grey area!” control the SSN, but different parts of it control tears than control saliva. Somewhere in there was something cool called DREADDs, but anyway.
Part of my take-home… I stand in ever greater awe of the incredible sophistication of the tear system, and how much science has yet to learn. (When you consider that the tear system is an essential part of the visual system, the complexity makes more sense.) Next time you see a dry eye doctor and find yourself frustrated with the lack of progress, think of this and cut them a little more slack than you might otherwise.
Next, Austin Mircheff’s presentation was all way, way over my head but gave interesting glimpses into underlying causes of dry eye… and a really interesting research approach. Apparently having carried a pregnancy to term increases Sjogrens Syndrome risk as much as twofold; and pregnancy increases the risk of dry eye without Sjogrens. So they asked the question: Does pregnancy influence gene expression? - believing that it should be possible to develop a preventive mechanism if you can get at the way this develops. The research presented was focused on two things then - environmental impact, and pregnancy impact.
After that, Sarah Hamm-Alvarez on tear biomarkers for Sjogrens syndrome. Did you know that Sjogrens is the second most common auto-immune disease in the US, but it still takes 4 years to diagnosis (down from 6 not all that long ago, though, which is good)? We are lacking in simple diagnostic tests for it and also specific treatments for it.
Dr Hirayama presented on advances in lacrimal gland organ regeneration. That’s such an exciting word. They described two different ways to go about it: (1) replace the organ with a fully functioning 3D bioengineered organ created from cells in vitro (demonstrated this with time lapse photography… I remember seeing something like this about meibomian glands at the TFOS meeting a few years back). Or (2) direct cell conversion to target cells. However they do it, it’s just so exciting that this is being worked on.
Dr Makarenkova wrapped up the session on implications of new research on lacrimal gland stem cells. Most of this was way beyond my reach but what I jotted down was that despite the lacrimal glands having plenty of regenerative potential, chronically inflamed lacrimal glands just don’t want to heal.
All in all, this was a wonderfully nerdy session, humanized by Dr Tsubota’s happy mice.