Making Tears Part 8 - More on Making Proteins…
A couple of posts ago, I referred to the intricate “bakeries” inside the castle walls (which I count as the Lacrimal Gland), where production of proteins like “Sir Lact,” “Sir Lyse” and a whole army of defensive “Knights” occur to keep the realm (the eye) safe. Outside the castle, there are the “rolling fields” of conjunctiva (the smooth, clear membrane covering the whites of the eyes) as well as the cornea (the window or “watch glass” we see through). Among that membrane field are tiny cells I referred to as the “Peasants” working that field. Served by blood vessels carrying proteins and other nourishing products, these Peasants (called Goblet cells”) can “belch out” a special, sticky protein, called mucus. Their distribution is not evenly spread across the landscape, but the “mixing action” of a blink can help distribute their sticky products over the surface of that realm. Because the surface would be very slippery without this “peanut butter-like substance” to help adhere, a key attribute of this product is the very sticky nature that interacts with the salt-watery tears floating above that layer and allows it to spread its goodness while acting as another barrier to any “badness” that would like to attack that surface. As sticky as it is to the cells below the tears, it has unique properties that makes it hard for germs to get to - and stick to - that surface!
The nose-favored distribution of the “Protein Factories” called “Goblet Cells.” (tiny dots are the cells with some clusters as larger dots. N stands for Nose).
From: Gipson IK. Goblet cells of the conjunctiva: A review of recent findings. Prog Retin Eye Res. 2016 Sep;54:49-63. doi: 10.1016/j.preteyeres.2016.04.005. Epub 2016 Apr 16. PMID: 27091323; PMCID: PMC4992623.
The Calcium “tokens” play a role in switching on the production of that sticky protein and the hormone messenger, Vitamin D, has receptors that it can bind to, and help in increasing the supply of Calcium - which can initiate greater protein production. Vitamin D has come under great medical interest, as it has similar mediating roles around the entire body - and the deficiencies of Vitamin D common to many of us in the North East, means many of my dry eye patients are at a disadvantage, since natural sources of Vitamin D come from exposure of the skin to the sun, and in this area winters are long, winter days are short and often cloudy. Primary care doctors are increasingly tuned in to monitoring Vitamin D levels and often recommend Vitamin D3 supplements. Cod liver oil, a prime source of Omega 3, is also a good source of Vitamin D and it is part of the supplements I recommend to most of my patients. Around the “mouth” of these goblet cells is a “belt-like” band that can help regulate the “belching,” by adjusting the size of the opening that would allow the proteins to escape (a bit like a chimney flue that regulates the escape of smoke from a fireplace). As the concentrated protein escapes, it mixes with water and “blooms” into the sticky paste we call mucin or mucus.
But Goblet cells are not just “protein factories,” indeed they appear responsible for the water expressed from the conjunctiva itself. Using my “sprinkler and fire hose” analogy, the Goblet cells produce “Claudins” a type of chemical “worker” that can open little water channels in the membranes of the Goblet cells and help regulate their “sprinkler function.” The Lacrimal Gland is the primary source for the dousing of salty water I refer to as the “fire hose” - so that water can really flow when it is most needed.
Production of these important Goblet cells, comes from unique stem cells - different but related to the stem cells that cover our corneas with their specialized cells. They have an interesting biological clock that produces crops of these “peasants” based on a cell-doubling calendar. Most of the time they crank out epithelial cells - the tough “tiles” that make up the resilient cover of our membrane, but at regular intervals, they switch gears to produce the Goblet cells! Inflammation appears to affect production of these Goblet cells - and allergies, infections and self-induced irritation (as in Mucus Fishing) are well known factors in increasing their protein production - see my post on this here: https://www.eyethera.com/blog/when-eyelids-are-irritated-including-allergies-such-as-to-our-best-friend-pets
Not all proteins produced by Goblet cells are the sticky things outlined above - some have additional sugar complexes that make them uniquely suited to assist in repair of the corneal surface (think of them as the medical emissaries or local “Red Cross” if such a thing existed in our Medieval world). Genetic tweaks in the production of similar Goblet cell proteins can lead to a real world autoimmune disease - Ocular Cicatricial Pemphigoid (OCP - mentioned in my autoimmune posting - now called “mucous membrane pemphigoid” - see the next link, below), where the surface progressively scars and can lead to exceptionally dry surfaces that can result in blindness for those not sufficiently diagnosed and treated.
Cyclosporine (medications like Restasis, among others) has anti-inflammatory properties that can lead to as much as a 2-fold increase in the number of Goblet cells (by reducing the inflammation that reduced that number), as well as an increased water production (and overall “sprinkler system” tear volume) for our tears. This appears relatively unique among anti-inflammatory medications and may be especially helpful for those patients suffering from reduced mucin (common to those with significantly advanced dry eye disease called “Aqueous Tear Deficiency” - see my prior posts on water, including: https://www.eyethera.com/blog/when-the-sprinkler-system-dries-up-and-autoimmune-testing-is-negative-whats-up ). Vitamin A also plays a role and while we know too much Vitamin A has been associated with MGD (Accutane for one), some amount is needed for proper Goblet cell development and activity. In fact, the brain-eye “axis” development is heavily dependent on Vitamin A from conception. Because Vitamin A can be produced as needed from a diet rich in leafy green vegetables, this appears yet one more reason to include these foods in your diet!
Many diseases wage war on Goblet cells - allergies, Autoimmune diseases (i.e. Stevens Johnson Syndrome, OCP, Sjogren’s, Graft vs Host) as well as advanced dry eye disease, radiation and even blepharitis (see my many posts on that issue). Keeping Goblet cells healthy is one more goal for dry eye doctors to have for their patients - those poor little Peasants are no less noble than the Knights, Kings and Queens, when it comes to keeping a healthy, happy realm.
To schedule an appointment with Dr. Jaccoma, call Excellent Vision at either of these two dry eye offices:
(1) 155 Griffin Rd, Portsmouth, NH 03801 (603) 574-2020
(2) 3 Woodland Rd, STE 112 Stoneham, MA 02180 (near Boston) (781) 321-6463