Lacritin is a 12.3 kDa glycoprotein encoded in humans by the LACRT gene. Lacritin is a secreted protein found in tears and saliva. Lacritin also promotes tear secretion and proliferation of some epithelial cells. Lacritin is thus a prosecretory mitogen.
Most lacritin is produced by the lacrimal gland. Some lacritin is produced by the meibomian gland, and also by epithelial cells of the conjunctiva and cornea. Together these epithelia comprise much of the lacrimal functional unit (LFU). Dry eye is the most common disease of the LFU. Preliminary studies with small trials suggest that lacritin may be differentially downregulated in dry eye, including contact lens-related dry eye. Topical lacritin promotes tearing in rabbit preclinical studies.
Lacritin cell targeting is dependent on the cell surface heparan sulfate proteoglycan syndecan-1 (SDC1). Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial heparanase (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein. A G-protein-coupled receptor (GPCR) then appears to be ligated. Targeted cells signal to NFAT and mTOR.
| Lacritin | |
|---|---|
| Abbreviation | LACRT |
| Sources | lacrimal, meibomian and salivary glands; corneal and conjunctival epithelia |
| Targets | epithelial specificity |
| Receptors | syndecan-1 (SDC1 but not SDC2 or SDC4) as coreceptor; requires active heparanase (HPSE) to expose a protein core binding site; Signaling receptor: a GPCR is suspected (lacritin mitogenic signaling is pertussis toxin inhibitable); Site of Binding: between N-terminus of SDC1 and C-terminus of lacritin |
| preclinical studies suggest utility in increasing ocular tearing | |