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Lactoferrin & Dry Eyes

Friday, September 28, 2012


Lactoferrin is an iron-binding protein found in milk. It is the main glycoprotein component of the middle watey layer of the tear film. Today's Pearl will mostly focus on lactoferrin's multi-function jobs including anti-inflammatory effects, tear film lipocalin balance, and inhibition of ocular surface bacterial biofilm formation. 

Lactoferrin, structurally similar to transferrins, is also known as lactotransferrin (LTF), a globular multifunctional protein with antimicrobial activity that is part of our bodies innate defense.
 
Transferrin is found in the mucosa, and binds iron creating an environment low in free iron that impedes bacterial survival in a process called iron withholding.  
 
Lactoferrin has been suggested in a number of peer-reviewed studies to  increase the level of iron binding proteins necessary to inhibit ocular surface  infections and to balance other tear film lipocalins (family of proteins that transport small hydrophobic molecules), that modulate the surface tension and osmolarity of the tear film, which affects ocular surface health and the comfort level of many contact lens wearers.
 
Lactoferrin taken orally avoids absorption in the stomach through pepsin-mediated digestive conversion to a very small molecule called lactoferricin, which is then transported into secretory tissues including the lacrimal gland.

Lactoferrin is also produced in the lacrimal gland by white blood cell neutrophils that constitute the "first line of defense" against infection.

Neutrophil apoptosis (programmed cell death) signals the macrophage to clean up debris from wound sites, including surgically induced wounds, as with LASIK. 

A recently published mouse study in the open-access peer-reviewed science journal, PLoS One, found that oral lactoferrin supplementation reduced inflammatory cell infiltration and the monocyte chemotactic protein-1  (MCP-1) and tumor necrosis factor-alpha-a (TNF-a) expression levels associated with induced dry eye disease.
 
MCP-1 is a gene that plays a role in the recruitment of white blood cell monocytes to sites of injury and infection.

As an aside:  MCP-1 has also been found in the joints of people with rheumatoid arthritis, where it may serve to recruit white blood cell macrophages that perpetuate the inflammation associated with joint pain. Elevated levels of the MCP-1 gene have also been found in the urine of people with lupus, which is a red flag warning of kidney inflammation. A number of studies have now been published linking lactoferrin to both joint and bone health.
 
TNF-a is a cytokine produced by activated white blood cell macrophages involved in systemic inflammation associated with the acute inflammatory phase.

It is not particularly surprising that a recent Chinese study also found that acupuncture  increased  lactoferrin levels in tears of dry eye patients. 

Another study that is interesting, but not surprising, looked at the effect of Ramadan fasting on tear proteins and found that  tear proteins, including lactoferrin, and tear enzymes  decreased during fasting.  

Nutritional deficiencies affect our entire body, including tear film biochemistry and visual acuity. 
   
Unfortunately, too many oral products designed to primarily address the lipid layer of the tear film do not address  tear film stability, biochemical balance, or nutritional function of natural tears with their complex composition including mucins, goblet cells, water, lipids, growth factor proteins, enzymes, neurotransmitters, vitamins, minerals, antioxidants, glucose and salts.

Ellen Troyer, MT MA
Biosyntrx CEO / Chief Research Officer  





PEARL

It's reasonable to suggest, given the amount of published science available, that a variety of nutrients  play a major role in tear film biochemical balance, including nutrients that affect aqueous output,  inflammatory markers, protein balance, osmolarity, surface tension, tear break up time (TBUT), ocular surface health and visual acuity.   

These necessary nutrients are included in Biosyntrx BioTears Oral GelCaps. 








References

  • Dietary lactoferrin alleviates age-related lacrimal gland dysfuntion in mice. Kawashima M, Kawakita T, et al. Plos One,2012: 7(3): e33148. [full study]

    Tear proteomics in evaporative dry eye diease. Versura P, Nanni P, et al. Eye, 2010 Aug; 24(8): 1396-402- [abstract]

    Effects of acupuncture on lactoferrin content in tears and tear secretion in patients suggering from dry eyes: a randomized controlled trial. Shi JL, iao WH. Zhong Xi Yi Jie He Xue Bao. 2012 Sep; 10:(9): 1803-8. [
    abstract]

    Effect of Ramadan fasting on tear proteins. Aarin R. Varasteh A, et al. Acta Medica 2010; 53(3): 147-51 [abstract]

    Tear lipocalins: potential lipid scavengers for the corneal surface. Glasgow BJ, Marshall G, Gasymov OK, Abduragimov AR, Yusifov TN, Knobler CM Invest Ophthalmol Vis Sci 1999 Dec;40(13):3100-7 [abstract]  

    The inhibition of mast cell activation by neutrophil lactoferrin: uptake by mast cells and interaction with tryptase, chymase and cathepsin G. HeS, McEven AR, blewell SA.Biochem Pharmacol 2003 Mar 15; 65 (6): 1007-15 [abstract]

    Components responsible for the surface tension of human tears. Nagyova B, Tiffany JM.Curr Eye Res 1999 Jul;19(1):4-11 [abstract]

    Lactoferrin down-regulates the LPS-induced cytokine production in monocytic cells via NFkappa B. Haversend L, Ohlsson BG, Hahn-Sone M. et al. Cell Immunol. 2002 Dec; 220 (2); 83-95 [abstract]  

    Bovine lactoferrin stimulates the phagocytic activity of human neutrophils: identification of its active domain. Miyacchi H, Hashimoto S, et al. Cell Immunol. 1998 Jul 10;187(1):34-7. [abstract]  

    What is dry eye and what does it mean to the contact lens wearer? Foulks, GN. Eye Contact Lens. 2003 Jan;29(1 Suppl):S96-100; discussion S115-8, S192-4. [abstract]