Article Date: 4/1/2010

Examining the Function of Tear Proteins
dry eye dx and tx

Examining the Function of Tear Proteins

BY WILLIAM D. TOWNSEND, OD, FAAO

When Eugene Wolff, author of the classic text Anatomy of the Eye and Orbit first described the tear film as being composed of three distinct layers, it's unlikely he realized the truly amazing complexity of tears. His theory was challenged by noted peers, such as Ehlers, who questioned the existence of a mucin layer overlying the corneal surface. There's still controversy over the tear film structure in terms of 2- versus 3-layer structures, and also in things as basic as how the lipid layer spreads over the aqueous component of the tears. Recent insights suggest that rather than the traditional model of polar lipids interfacing between the aqueous and nonpolar lipids, tear film proteins may play a role in altering surface tension, allowing for this interface to occur. Additional research is needed to understand these fundamental issues. Our tools for investigating the individual components of the tear film have expanded exponentially, and our knowledge about the presence and function of tear proteins has rapidly advanced.

Recent studies reveal noticeable changes in tear proteins in certain disease states, such as diabetes. Gel electrophoresis demonstrates significant differences between the protein peaks in diabetics compared to nondiabetics and reveals altered protein profiles in diabetic patients who have dry eye and in those who have normal tear composition, suggesting that the tears of diabetics contain new or altered proteins not found in nondiabetic subjects. These biomarkers may be used to monitor diabetic disease. Further analysis revealed that alterations in tear proteins were proportional to duration of diabetes. We may use these atypical tear proteins to monitor diabetes, predict the likelihood of retinopathy, or as a noninvasive tool to identify conditions associated with diabetes.

Over 400 intracellular and extracellular proteins are found in the tear film. Wu and colleagues (2006) proposed mechanisms for protein production and release by secretory granules into tears. Some functions of tear proteins include regulation of angiogenesis, bio-synthesis, carbohydrate metabolism, cell adhesion/motility, growth, immune status and lipid metabolism. There's tremendous interest in understanding how these proteins are altered in presence, structure or function in ocular surface disease conditions such as dry eye disease. Recent studies demonstrate that lacritin, a pro-secretory mitogen protein, is continuously down-regulated in dry eye.

If down-regulation of tear proteins is causative or associated with dry eye disease, it's theoretically possible to use recombinant DNA technology to generate deficient proteins. Similar technology is used to treat cancer, vascular disease, neurologic conditions and anemia. Two recombinant DNA molecules already used in eye care are bevacizumab (Avastin) and ranibizumab (Lucentis), both from Genentech.

Recombination is accomplished through several different methods. One technique works by selecting a segment of DNA and injecting it into a specific site on bacterial DNA. The bacterial cells are used as hosts to make protein, which is purified and stored. The first use of this technology was bacterial production of human insulin.

Future ocular applications may permit us to identify specific proteins lacking in an individual's tear film and use recombinant proteins to personalize treatment for each patient's dry eye or other ocular surface disease. CLS

For references, please visit www.clspectrum.com/references.asp and click on document SE2010.


Dr. Townsend is a member of the executive board of the Ocular Surface Society of Optometry (OSSO) a non-profit, independent organization founded with the mission of increasing awareness and advancing the understanding and management of dry eye and ocular surface disease among Optometric practitioners, industry, and other health care providers.

Contact Lens Spectrum, Issue: April 2010