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Eyes on the Prize
“Normally, lacritin is not detected in tissues not associated with the eye. Resources for studying the eye and associated tissues are generally much more limited than with other organs. This explains why others did not discover it first,” Laurie says. “We have an entry-level idea of how lacritin works. Members of the consortium discovered that lacritin targets the eye cells through a completely novel ‘off/on’ switching mechanism that is activated by an enzyme. After this receptor switch, there is a ‘domino’ signaling effect within the cells. Identifying each of the dominos is essential because they may dovetail in positive or negative way with other signaling pathways stimulated by drugs, or even by a few of the other proteins in tears.” The consortium’s research findings have been published in the Journal of Molecular Biology and in two articles in the Journal of Cell Biology. Founded in 2002, the consortium combines researchers from UVA, James Madison University (protein engineers Robert McKown, Ph.D. and Ron Raab, Ph.D.) and Eastern Virginia Medical School (Patricia Williams’ Ph.D. lab performs preclinical testing). Along with potential treatments for dry eyes, the discovery of lacritin could also aid medical procedures. UVA biomedical engineer Ed Botchwey, Ph.D. began developing a lacritin-infused contact lens as a potential bandage for refractive eye surgery for Col. Scot Bower, M.D. at Walter Reed Army Medical Center, who heads up this procedure for the U.S. Army. The biggest challenge in working with lacritin, Laurie says is that biological proteins are difficult to develop in the lab. Manufacturing the proteins, keeping them stable, transporting them to patients and delivering them to the eye are all under investigation. Successfully tackling these issues – which could take several years – could lead to effective treatments for dry eyes. Laurie is encouraged by what the discovery of lacritin could mean for the work of medical researchers. “Lacritin is uncovering exciting new features about epithelial cell biology,” he says.
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Funded by two grants to UVA from the National Eye Institute, including a recent $2.1 million award, much of the effort focused on better understanding lacritin. Lacritin is produced by the lacrimal gland, cornea and conjunctiva of the eye. Lacritin seems to help stimulate creation of the protective three-layer tear film as it flows through tear ducts onto the surface of the eye. It also acts as a shield against inflammation-associated cell death. Under certain conditions it also caused some cells to divide, suggesting that lacritin is a growth factor.