discovering dry eye
IgA through IgM: A Closer Look at Tear Proteins
BY JULIA RAE GELDIS, OD, & JASON J. NICHOLS, OD, MPH, PHD
Most tear proteins enter the tear fluid through conjunctival surface capillaries. Each carries out important functions. Albumin, transferrin and immunoglobulin G occur in very low levels in the tears and are at their highest levels in nonstimulated tears.
Lacrimal gland proteins include IgA, IgM, lactoferrin, lysozome and IgE. Like the ocular surface blood vessel proteins, these also decline with stimulation of tearing.
Tear Protein Functions
Why do we need tear proteins and what is their importance to our tear film? IgG provides immunity against blood-borne diseases, whereas albumin provides osmotic pressure and transferrin is involved in iron transport.
The tears contain specific IgA antibodies to a number of different antigens, including herpes simplex virus, Epstein-Barr virus, human immunodeficiency virus, adenovirus, Streptococcus epidermidis and Chlamydia trachomatis.
Lactoferrin may make up about 25 percent of human tear proteins. It binds iron, thus rendering it unavailable for bacterial metabolism. Lactoferrin also prevents the formation of hydroxyl radicals that would otherwise contribute to an inflammatory effect at the ocular surface.
Lysozyme has a direct bacteriolytic effect, unlike lactoferrin's more stealthy approach. However, lysozyme's bacteriolytic mechanism is effective only on a limited range of Gram-positive bacteria.
Tear IgM is active in the early immune response and enhances phagocytosis. Secretory IgM appears in the tear fluid of IgA-deficient patients. Tear IgE is a lacrimal gland tear protein whose levels are significantly elevated in various types of allergic conjunctivitis.
The last five years have brought new insights into the roles of tear proteomics and dramatic new understandings in the overall number of tear film proteins. Research has suggested at least 500 proteins in the tear film. While there probably aren't that many, the ocular surface has quite a protein presence to help ensure ocular surface integrity, leading to maximal visual function.
Research has revealed new tear film protein functions over the past several years, including their roles as lipid scavengers and surfactants.
Lipocalin, for example, may act as a physiological scavenger of potentially harmful lipophilic substances. It may also help maintain tear film stability. Lipocalin levels, as well as the levels of lacritin precursor, are significantly reduced in meibomian gland dysfunction.
In a host of dry eye diseases, membrane-associated mucins are altered and aren't as efficient in preventing lipid binding to the surface of the cornea, thus leaving the lipids available to eventually desiccate the corneal epithelium. This is where tear lipocalin steps in by binding the harmful lipids. This lipid scavenging role is an important function to consider as we continue to search for new, innovative ways to provide relief to our dry eye patients.
Proline rich proteins are also big names in the world of tear film proteomics these days. These proteins are thought to mediate modulation of ocular surface microflora. In the article "Measuring Tear Film Integrity" from the November 2005 supplement Exploring the Science of Solutions, Franz Grus, MD, PhD, reported a downregulation of proline rich proteins in a group of dry eye subjects.
For references, please visit www.clspectrum.com/references.asp and click on document #130.
Dr. Geldis is a cornea and contact lens advanced practice fellow at The Ohio State University College of Optometry. Dr. Nichols is an assistant professor of optometry and vision science at The Ohio State University College of Optometry.