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Beyond Lipids: Ocular Surface Mucin Refresher

Friday, March 31, 2017


Biosyntrx has always been focused on the biochemical structure and function role that each important layer of the tear film plays in ocular surface health and visual acuity.


Today we feature a mini mucin refresher that includes information from a 2004 Friday Pearl, plus some newer information from a brilliant 2016 Ocular Surface article by Anna Ablamowicz, OD, and Jason J. Nichols, OD, MPH, PhD, titled "Ocular Surface Membrane-Associated Mucins."


Friday Pearl: March, 2004 


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. These are are 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 and affect ocular 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 ocular surface 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.


There is a close relationship between vitamin A status and the expression of mucins.

 

It is also 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. 


2016: "Membrane-Associated Mucins" 


Secreted mucins are now classified into two main types: gel-forming or 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 newer 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, David Amess and the Biosyntrx staff



PEARL

We strongly recommend that our readers with a passionate professional or personal interest in mucin biochemistry, ocular surface health and tear film dependent visual acuity 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 structure / function information not discussed in today's Friday Pearl. The full article can be accessed through ScienceDirect.










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