Researchers identified lacritin, a novel glycoprotein almost exclusively produced by tear glands, that enhances tear secretion and promotes cell growth in the eye surface system.
Detected in only 3 of 50+ tissuesLacritin is remarkably tissue-specific — highly expressed in tear glands, moderately in salivary glands, and slightly in thyroid, with no detection elsewhere
What the researchers found
Lacritin is a newly identified secreted glycoprotein that is highly expressed in human lacrimal gland, moderately in salivary glands, and slightly in thyroid, with no detectable expression in more than 50 other tissues examined.
Recombinant lacritin enhanced unstimulated (constitutive) secretion from lacrimal acinar cells in culture, promoted ductal cell proliferation, and stimulated signaling through tyrosine phosphorylation and calcium release in corneal epithelial cells. It binds several extracellular matrix proteins including collagen IV, laminin-1, and fibronectin. The lacritin gene maps to chromosome 12q13 and consists of five exons with no alternative splicing.
Why it matters
Dry eye disease affects hundreds of millions of people worldwide, and current treatments mostly just supplement tears rather than addressing the underlying biology. The discovery of lacritin — a naturally occurring protein that specifically enhances tear production — opens a potential therapeutic avenue for treating dry eye at its source by restoring the gland's own secretory function.
How the study worked
The researchers used cDNA and genomic cloning techniques to identify and characterize the lacritin gene. They examined mRNA and protein expression across more than 50 human tissues using in situ hybridization and immunohistochemistry. Functional studies used overnight cultures of rat lacrimal acinar cells to test lacritin's secretion-enhancing effects, and recombinant lacritin was applied to measure its impact on ductal cell proliferation and corneal epithelial cell signaling.
What this study cannot tell us
This is a discovery and characterization study using cell culture systems and animal tissue, not a clinical trial. The secretion-enhancing effects were demonstrated in overnight cultures of rat acinar cells, which may not fully reflect in vivo human biology. The study establishes lacritin's existence and basic functions but does not test therapeutic applications. The tissue expression survey, while broad, relied on available human tissue samples.
How to read the evidence
This is a basic science discovery paper using cell culture and molecular biology techniques. It establishes the existence and basic properties of lacritin but provides no clinical evidence. Evidence strength is low for therapeutic applicability but foundational for the field.
When this study was published
Published in 2001, this is the original discovery paper for lacritin. While over two decades old, it remains the seminal reference for all subsequent lacritin research, including ongoing therapeutic development for dry eye.
The bigger picture
Lacritin's discovery filled a significant gap in understanding how the lacrimal gland maintains tear production. Since its identification in 2001, subsequent research has explored lacritin as a potential therapeutic for dry eye disease, including studies on topical lacritin formulations. It represents a broader shift toward treating secretory dysfunction by targeting the gland's own regulatory proteins rather than just replacing the missing fluid.
Questions still open
- Could topical or local administration of lacritin restore tear production in patients with dry eye disease?
- What receptor does lacritin bind on lacrimal acinar cells to enhance secretion?
- Why is lacritin expression so remarkably tissue-specific, and what regulates its expression in the lacrimal gland?
Common questions
What is lacritin and why is it important for eye health?
Could lacritin be used to treat dry eye disease?
Read the original research
cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland.
Journal of molecular biology, 310(1), 127-39
Citation
Sanghi, S; Kumar, R; Lumsden, A; Dickinson, D; Klepeis, V; Trinkaus-Randall, V; Frierson, H F; Laurie, G W. (2001). cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland.. Journal of molecular biology, 310(1), 127-39.