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Ocular Surface Mucins: Then and Now

Friday, May 20, 2016


We started writing tear film mucin Friday Pearls back in 2004, as seen in the one below titled “MUC4 Does Not Mean the Speed of Sound.” We included that 2004 Friday Pearl in today's Pearl, plus information from an interesting new article in The Ocular Surface by Anna Ablamowicz, OD, and Jason J. Nichols, OD, MPH, PhD, from the School of Optometry, University of Alabama at Birmingham. It's titled "Ocular Surface Membrane-Associated Mucins."

March 2004, Biosyntrx Friday Pearl: Since the mid-1990s, a large number of mucin (MUC) genes have been identified: MUC1, MUC2, MUC4, MUC5A, MUC5B, MUC7 MUC13, MUC15, MUC16 and MUC17 are the genes now associated with the ocular surface mucins and the tear film.

Mucins are nutrient dependent glycoproteins expressed by epithelial tissues of mucosal surfaces. Mucins are classified as either secretory or membrane spanning, and the tear film and ocular epithelium contain both types. Recent studies suggest that the tear film is actually five to seven times thicker than previously thought, with the mucus layer comprising most of the thickness.

Ocular mucins protect against bacterial adherence to the corneal epithelium, and alterations in mucus production promote bacterial adherence to the cornea. A deficiency in mucin production can lead to decreased tear break-up time, which affects ocular surface health. 

Currently, the proposed sources of ocular mucin include the conjunctival goblet cells, conjunctival, corneal epithelial cells and lacrimal gland, as well as ocular surface wound healing growth factors (epidermal and transforming) that may stimulate goblet cell mucin secretion.

Origins and secretion of mucins

MUC1, MUC4 and MUC16 are membrane-spanning mucins with a hydrophobic amino acid segment that allows the mucin core protein to remain intimately associated with the epithelial cells.

MUC2, MUC5A, MUC5B are secretory mucins that overlay the ocular surface and provide structure for lubrication as well as protection to the cells.

MUC7 is a smaller peptide-soluble secretory mucin that does not form a gel but provides mechanisms for efficiently mixing all the secretory mucins in the aqueous layer of the tear film.

MUC13, MUC15 and MUC17 have been proven to exist in human conjunctival epithelium from healthy donors. The exact function of these genes remains to be further elucidated.

The ocular surface epithelium has a major requirement for vitamin A, and a deficiency in this vitamin causes loss of the corneal microvilli and reduces the number of conjunctival goblet cells.

It is now suggested that the MUC5AC gene secretion is also stimulated by an intracellular influx of calcium or that this ion may serve as a common intracellular pathway for mucin secretion in response to various stimuli.

June, 2016, The Ocular Surface: "Ocular Surface Membrane-Associated Mucins" Secreted mucins are now classified into two main types: 1) gel-forming and 2)  small soluble. On the ocular surface, the goblet cells in the conjunctiva synthesize MUC5AC and secrete it into the tear film as the base layer scaffold.

This mucin forms disulfide bonds due to cysteine-rich regions that create protein mucus complexes. Another goblet-cell-produced, lower-weight MUCAC is presumably to prevent viscous mucus scattering of light.

Mixed with the aqueous component of the tear film, the secreted mucins on the ocular surface are able to trap and move debris to the puncta for removal with every blink.

Membrane-associated mucins (MAMs) on the ocular surface (MUC1, MUC4 and MUC6) project from microplicae found on the anterior surface of corneal and conjunctival epithelial cells.

These mucins provide a surface over which the tear film can glide and effectively hydrate the ocular surface. MUC1 may play a role in bacterial adhesion and possibly wound healing, however MUC16 is now suggested to play a greater role in barrier function than MUC1.

Summary and conclusions from the new Ocular Surface article

“While mucins cover all wet-surfaced epithelia in the body, those that are expressed on the ocular surface have vital functions in protecting sight. In order to provide a stable refractive surface through which light can be transmitted to the retina, the ocular surface must maintain important balances in hydration and lubrication as well as protection against pathogens and mechanical damage due to exposure to the environment.”

Ellen Troyer, with Spencer Thornton, MD, and the Biosyntrx staff


PEARL

We strongly recommend that our readers with a professional or personal interest in mucins and dry eyes take the time to read the full The Ocular Surface article, since it covers biosynthesis of mucins, glycocalyx (outer covering of many cells) and additional interesting mucin information not discussed in today's Friday Pearl.

FYI: Our Friday Pearl supporting bibliographic citations are no longer available on our website.This is to meet FDA-monitored federal regulations that prevent supplement companies from using educational peer-reviewed science from the U.S. National Institutes of Health National Library of Medicine to encourage eye and body health. The citations are available for medical professionals in the Biosyntrx office. 

If you view this as a possible government "Freedom of Information Act" issue, we recommend graciously contacting your elected state representatives and voicing your concern.









Crestpoint Management, LTD instrument announcement:
Nucleus Manipulator, Ball Shaped Tip 6-472-3

Bibliography

Clinical references available in the Biosyntrx office.