Lacritin, a tear protein that is selectively depleted in dry eye disease, can promote natural tear production when applied topically and may offer a more targeted treatment than current palliative approaches.
Selectively deficientLacritin and lipocalin-1 are among only a handful of tear proteins specifically reduced in dry eye, making them prime candidates for targeted replacement therapy.
What the researchers found
Lacritin and lipocalin-1 are two tear proteins selectively deficient in dry eye disease. Lacritin is a prosecretory mitogen — meaning it both stimulates tear secretion and promotes cell growth — and has been shown to promote basal tearing when applied topically as a recombinant protein.
Active monomeric lacritin levels are suppressed by tear tissue transglutaminase, an enzyme whose expression is elevated in dry eye patients with ocular surface inflammation. Lipocalin-1 serves as the primary lipid-absorbing molecule of the tear film, preventing residual lipids from disrupting the eye surface wetting layer. It also functions as a carrier for vitamins and steroid hormones and as an endonuclease that clears potentially proinflammatory DNA from tears.
Why it matters
Current dry eye treatments are largely palliative, offering temporary relief without targeting the root cause. Identifying specific tear proteins that are depleted in dry eye opens the door to biotherapeutic approaches that could restore normal tear function rather than simply masking symptoms. This research shifts the treatment paradigm from generic lubrication to precision replacement of missing biological components.
How the study worked
This was a narrative review examining the tear proteome — the complete set of proteins found in tears — with a focus on lacritin and lipocalin-1 biology. The authors synthesized findings from proteomic studies, functional assays, and preclinical experiments to discuss the therapeutic potential of tear protein replacement.
What this study cannot tell us
This is a review article, not a clinical trial, so it synthesizes existing evidence rather than presenting new patient data. The therapeutic potential of topical lacritin has been demonstrated in preclinical models but had not yet been validated in large-scale human clinical trials at the time of publication. The specific mechanisms by which protein-protein interactions in the tear film affect function are not fully understood.
How to read the evidence
This is a narrative review that synthesizes prior research on tear proteomics and lacritin biology. It provides a strong conceptual framework but does not present new clinical trial data, placing it below primary research in evidence hierarchy.
When this study was published
Published in 2013, this review laid important groundwork for lacritin as a biotherapeutic. Since then, lacritin research has continued to advance, and the concepts discussed remain relevant to current dry eye drug development efforts.
The bigger picture
This research sits at the intersection of proteomics and ophthalmology, part of a broader movement toward biologic therapies that replace what the body is missing rather than using synthetic substitutes. If tear protein replacement proves effective in clinical trials, it could fundamentally change how dry eye is treated — and the approach could extend to other mucosal surface diseases where specific protective proteins are depleted.
Questions still open
- Can recombinant lacritin be manufactured at scale and formulated as a stable eye drop for widespread clinical use?
- Would combining lacritin and lipocalin-1 replacement produce better outcomes than either protein alone?
- How does the inflammatory enzyme tissue transglutaminase inactivate lacritin, and could blocking this enzyme be another treatment strategy?
Common questions
What is lacritin and why is it important for dry eye?
How is this different from regular artificial tears?
Read the original research
Lacritin and the tear proteome as natural replacement therapy for dry eye.
Experimental eye research, 117, 39-52
Citation
Karnati, Roy; Laurie, Diane E; Laurie, Gordon W. (2013). Lacritin and the tear proteome as natural replacement therapy for dry eye.. Experimental eye research, 117, 39-52. https://doi.org/10.1016/j.exer.2013.05.020