Lacritin
Encyclopedia
Lacritin is a 12.3 kDa glycoprotein
encoded in humans by the LACRT gene
. Lacritin is a secreted protein found in tear
s 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.
and displays several predicted alpha helices, mostly in the C-terminal half. At least one appears to be amphipathic with hydrophobic
and hydrophilic
residues on opposite faces. The hydrophobic face likely forms the binding site
for syndecan-1. PONDR (Predictor of Naturally Disordered Regions) predicts that the C-terminal and N-terminal halves are respectively 'ordered
' and 'disordered'. 11 - 12 predicted O-glycosylation sites populate the N-terminal half. One putative amphipathic alpha helix near the C-terminus may be responsible for binding the N-terminus of syndecan-1, and is the site of lacritin's only N-glycosylation site. In 'climatic droplet keratopathy' this site appears to be unglycosylated. Predicted pI of lacritin's core protein is 5.
Several lacritin splice variants
have been detected in Aceview, from NEIBank EST data. Lacritin-b (11.1 kDa; pI 5.3) lacks the sequence SIVEKSILTE. Lacritin-c (10.7 kDa; pI 4.6) displays a novel C-terminus that should be incapable of binding syndecan-1. Both may be null forms of lacritin.
of the human tear film. It is mainly produced by the lacrimal gland
. Some lacritin also is produced by the meibomian gland
, and also by epithelial cells of the conjunctiva
and cornea
. The lacritin gene (LACRT) is one of the most transcriptionally regulated gene
s in the human eye
. Functional studies suggest a role in epithelial renewal of some nongermative epithelia. By flowing downstream through ducts, it may generate a 'proliferative field'. Lacritin also promotes secretion
. This raises the possibility that lacritin may have clinical applications in the treatment of dry eye, the most common eye disease. Recent studies suggest that lacritin is differentially downregulated in blepharitis
.
Lacritin is an LFU prosecretory mitogen with a biphasic
dose response that is optimal at 1 - 10 nM for human recombinant
lacritin on human cells. Higher human lacritin concentrations are optimal on rat or mouse cells or on rabbit eyes. Lacritin flows downstream from the lacrimal gland
through ducts onto the eye
.
syndecan-1 is partly responsible. Syndecan-1 binds many growth factors through its heparan sulfate
side-chains. It also binds lacritin, but heparan sulfate interferes with lacritin binding. Since syndecans are always decorated with heparan sulfate, this means that heparanase
must be available to partially or completely cleave off heparan sulfate, allowing lacritin to bind. Indeed, siRNA
studies without and with rescue demonstrated that heparanase regulates lacritin function.
Biotinylated cell surface proteins from a lacritin-responsive cell were incubated with lacritin under conditions of physiological salt. Those that bound lacritin were sequenced by mass spectrometry
. Few bound. The most prominent was syndecan-1 (SDC1). In confirmatory pull-down assays, binding was not shared with family members syndecan-2
or syndecan-4
, indicating that the protein core (and not the negatively charged heparan sulfate side-chains) was the main site of binding. Further analysis narrowed the site to syndecan-1's N-terminal 51 amino acids. Syndecan-1 is widely expressed on epithelial and other cell types. How is this mechanism cell-specific? The answer appears to be the restricted availability of active epithelial heparanase
(HPSE) that serves as an 'off-on' switch for lacritin binding. This novel mechanism appears at first glance to be poor for ocular health, since heparanase release from invading lymphocytes in the corneal stroma is inflammatory. Yet heparanase is a normal secretory product of the corneal epithelium. Likely it is largely latent and activation may be local.
Lacritin mitogenic signaling follows two pathways:
Rapid dephosphorylation of PKCα causes it to transiently move from the cytoplasm to the area of the Golgi apparatus and peripheral nucleus. Here, it forms a complex with PKCα and PLCγ2 from which downstream mTOR and NFAT signaling is initiated.
The upstream Gαi or Gαo signaling suggests the involvement of a G-protein-coupled receptor (GPCR). A candidate GPCR is under study. Syndecan-1 likely serves as a co-receptor. Binding lacritin may improve its GPCR affinity.
reveals the existence of putative lacritin orthologues in other species including: Dasypus novemcinctus (nine-banded armadillo), Echinops telfairi (lesser hedgehog), Felis silvestris catus (house cat), Macaca mulatta (rhesus macaque or monkey), Myotis lucifugus (little brown bat), Pan troglodytes (chimpanzee), Sorex araneus (common shrew), and Tupaia belangeri (northern tree shrew). PONDR and O-glycosylation patterns are similar.
, moderately in salivary gland
s and slightly in mammary
(cancer but not or rarely normal), and thyroid gland
s. The salivary gland
expression can be attributed to a discrete group of unidentified ductal-like cells. Some lacritin was reported in lung bronchoalveolar lavage. In lacrimal gland, polarized lacrimal acinar cells appear to be the most prolific lacritin producers, as evidenced by strong staining of secretory granules in keeping with lacritin release after carbachol stimulation. Carbachol-dependent release involves PKC and calcium signaling. Some lacritin is produced by the meibomian gland
, and also by epithelial cells of the conjunctiva
and cornea
that together with lacrimal gland comprise much of the lacrimal functional unit (LFU). Viewed collectively, the LFU is the primary source of lacritin in the body, and the eye
the main target.
Some changes have been noted in disease. Dry eye is the most common eye disease. Preliminary studies with small trials suggest that lacritin may be differentially downregulated in dry eye. In climatic droplet keratopathy, N119 appears to be unglycosylated. Also a normal breast cancer
localization reported by some has not been replicated in Unigene
(the 'mammary gland
' hit is for breast cancer) and gene array studies, but some breast cancers appear to display elevated expression or LACRT gene amplification.
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
encoded in humans by the LACRT gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Lacritin is a secreted protein found in tear
Tear
Tear may refer to:*Tears, a type of eye secretion*Tearing, the ripping apart of something by force*Robert Tear, a Welsh singer-Elements in fiction:*Tear, a character Tear Grants in video game Tales of the Abyss...
s and saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
. Lacritin also promotes tear secretion and proliferation
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
of some epithelial cells. Lacritin is thus a prosecretory mitogen
Mitogen
A mitogen is a chemical substance that encourages a cell to commence cell division, triggering mitosis. A mitogen is usually some form of a protein.Mitogenesis is the induction of mitosis, typically via a mitogen....
.
Most lacritin is produced by the lacrimal gland
Lacrimal gland
The lacrimal glands are paired almond-shaped glands, one for each eye, that secrete the aqueous layer of the tear film. They are situated in the upper, outer portion of each orbit, in the lacrimal fossa of the orbit formed by the frontal bone. Inflammation of the lacrimal glands is called...
. Some lacritin is produced by the meibomian gland
Meibomian gland
The meibomian glands are a special kind of sebaceous gland at the rim of the eyelids inside the tarsal plate, responsible for the supply of meibum, an oily substance that prevents evaporation of the eye's tear film. They prevent tear spillage onto the cheek, trapping tears between the oiled edge...
, and also by epithelial cells of the conjunctiva
Conjunctiva
The conjunctiva covers the sclera and lines the inside of the eyelids. It is composed of rare stratified columnar epithelium.-Function:...
and cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
. 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
Heparan sulfate
Heparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins...
proteoglycan
Proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan chain. The point of attachment is a Ser residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge...
syndecan-1
Syndecan 1
Syndecan 1 is a protein which in humans is encoded by the SDC1 gene.- Function :The protein encoded by this gene is a transmembrane heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family...
(SDC1). Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial heparanase
Heparanase
Heparanase, also known as HPSE, is an enzyme that acts both at the cell-surface and within the extracellular matrix to degrade polymeric heparan sulfate molecules into shorter chain length oligosaccharides.-Synthesis and structure:...
(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
NFAT
Nuclear factor of activated T-cells is a general name applied to a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system...
and mTOR.
Structure
Lacritin consists of 119 amino acids after cleavage of the N-terminal signal peptideSignal peptide
A signal peptide is a short peptide chain that directs the transport of a protein.Signal peptides may also be called targeting signals, signal sequences, transit peptides, or localization signals....
and displays several predicted alpha helices, mostly in the C-terminal half. At least one appears to be amphipathic with hydrophobic
Hydrophobe
In chemistry, hydrophobicity is the physical property of a molecule that is repelled from a mass of water....
and hydrophilic
Hydrophile
A hydrophile, from the Greek "water" and φιλια "love," is a molecule or other molecular entity that is attracted to, and tends to be dissolved by water. A hydrophilic molecule or portion of a molecule is one that has a tendency to interact with or be dissolved by, water and other polar substances...
residues on opposite faces. The hydrophobic face likely forms the binding site
Binding site
In biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands—form a chemical bond...
for syndecan-1. PONDR (Predictor of Naturally Disordered Regions) predicts that the C-terminal and N-terminal halves are respectively 'ordered
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
' and 'disordered'. 11 - 12 predicted O-glycosylation sites populate the N-terminal half. One putative amphipathic alpha helix near the C-terminus may be responsible for binding the N-terminus of syndecan-1, and is the site of lacritin's only N-glycosylation site. In 'climatic droplet keratopathy' this site appears to be unglycosylated. Predicted pI of lacritin's core protein is 5.
Several lacritin splice variants
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
have been detected in Aceview, from NEIBank EST data. Lacritin-b (11.1 kDa; pI 5.3) lacks the sequence SIVEKSILTE. Lacritin-c (10.7 kDa; pI 4.6) displays a novel C-terminus that should be incapable of binding syndecan-1. Both may be null forms of lacritin.
Function
Lacritin is a glycoproteinGlycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
of the human tear film. It is mainly produced by the lacrimal gland
Lacrimal gland
The lacrimal glands are paired almond-shaped glands, one for each eye, that secrete the aqueous layer of the tear film. They are situated in the upper, outer portion of each orbit, in the lacrimal fossa of the orbit formed by the frontal bone. Inflammation of the lacrimal glands is called...
. Some lacritin also is produced by the meibomian gland
Meibomian gland
The meibomian glands are a special kind of sebaceous gland at the rim of the eyelids inside the tarsal plate, responsible for the supply of meibum, an oily substance that prevents evaporation of the eye's tear film. They prevent tear spillage onto the cheek, trapping tears between the oiled edge...
, and also by epithelial cells of the conjunctiva
Conjunctiva
The conjunctiva covers the sclera and lines the inside of the eyelids. It is composed of rare stratified columnar epithelium.-Function:...
and cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
. The lacritin gene (LACRT) is one of the most transcriptionally regulated gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s in the human eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
. Functional studies suggest a role in epithelial renewal of some nongermative epithelia. By flowing downstream through ducts, it may generate a 'proliferative field'. Lacritin also promotes secretion
Secretion
Secretion is the process of elaborating, releasing, and oozing chemicals, or a secreted chemical substance from a cell or gland. In contrast to excretion, the substance may have a certain function, rather than being a waste product...
. This raises the possibility that lacritin may have clinical applications in the treatment of dry eye, the most common eye disease. Recent studies suggest that lacritin is differentially downregulated in blepharitis
Blepharitis
Blepharitis is an ocular condition characterized by chronic inflammation of the eyelid, the severity and time course of which can vary. Onset can be acute, resolving without treatment within 2–4 weeks , but more generally is a long standing inflammation varying in severity...
.
Lacritin is an LFU prosecretory mitogen with a biphasic
Biphasic
A biphasic system is one which has two phases.* In the physical sciences, a liquid water and steam system would represent a biphasic system. See phase ....
dose response that is optimal at 1 - 10 nM for human recombinant
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
lacritin on human cells. Higher human lacritin concentrations are optimal on rat or mouse cells or on rabbit eyes. Lacritin flows downstream from the lacrimal gland
Lacrimal gland
The lacrimal glands are paired almond-shaped glands, one for each eye, that secrete the aqueous layer of the tear film. They are situated in the upper, outer portion of each orbit, in the lacrimal fossa of the orbit formed by the frontal bone. Inflammation of the lacrimal glands is called...
through ducts onto the eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
.
Signaling
One particularly remarkable feature about lacritin is its cell targeting specificity. Lacritin targets a restricted group of epithelial cells (including human corneal epithelia), and not fibroblastic, glioma or lymphoblastic cells. New studies suggest that the cell surface proteoglycanProteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan chain. The point of attachment is a Ser residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge...
syndecan-1 is partly responsible. Syndecan-1 binds many growth factors through its heparan sulfate
Heparan sulfate
Heparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins...
side-chains. It also binds lacritin, but heparan sulfate interferes with lacritin binding. Since syndecans are always decorated with heparan sulfate, this means that heparanase
Heparanase
Heparanase, also known as HPSE, is an enzyme that acts both at the cell-surface and within the extracellular matrix to degrade polymeric heparan sulfate molecules into shorter chain length oligosaccharides.-Synthesis and structure:...
must be available to partially or completely cleave off heparan sulfate, allowing lacritin to bind. Indeed, siRNA
Sírna
Sírna Sáeglach , son of Dian mac Demal, son of Demal mac Rothechtaid, son of Rothechtaid mac Main, was, according to medieval Irish legend and historical tradition, a High King of Ireland...
studies without and with rescue demonstrated that heparanase regulates lacritin function.
Biotinylated cell surface proteins from a lacritin-responsive cell were incubated with lacritin under conditions of physiological salt. Those that bound lacritin were sequenced by mass spectrometry
Mass spectrometry
Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...
. Few bound. The most prominent was syndecan-1 (SDC1). In confirmatory pull-down assays, binding was not shared with family members syndecan-2
SDC2
Syndecan-2 is a protein that in humans is encoded by the SDC2 gene.-Interactions:SDC2 has been shown to interact with Laminin, alpha 3, EZR and CASK.-Further reading:...
or syndecan-4
SDC4
Syndecan-4 is a protein that in humans is encoded by the SDC4 gene.- Gene :This gene is found on chromosome 20, while a pseudogene has been found on chromosome 22.- Function :...
, indicating that the protein core (and not the negatively charged heparan sulfate side-chains) was the main site of binding. Further analysis narrowed the site to syndecan-1's N-terminal 51 amino acids. Syndecan-1 is widely expressed on epithelial and other cell types. How is this mechanism cell-specific? The answer appears to be the restricted availability of active epithelial heparanase
Heparanase
Heparanase, also known as HPSE, is an enzyme that acts both at the cell-surface and within the extracellular matrix to degrade polymeric heparan sulfate molecules into shorter chain length oligosaccharides.-Synthesis and structure:...
(HPSE) that serves as an 'off-on' switch for lacritin binding. This novel mechanism appears at first glance to be poor for ocular health, since heparanase release from invading lymphocytes in the corneal stroma is inflammatory. Yet heparanase is a normal secretory product of the corneal epithelium. Likely it is largely latent and activation may be local.
Lacritin mitogenic signaling follows two pathways:
- GαiGi alpha subunitGi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :The following G protein-coupled receptors couple to the Gi subunit:* Acetylcholine M2 & M4 receptors...
or Gαo → PKCαPKC alphaProtein kinase C alpha , also known as PRKCA, refers to both a human gene and the protein that is encoded by it.-Background:...
/PLCγ2PLCG21-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-2 is an enzyme that in humans is encoded by the PLCG2 gene.- Function :Enzymes of the phospholipase C family catalyze the hydrolysis of phospholipids to yield diacylglycerols and water-soluble phosphorylated derivatives of the lipid...
→ Ca2+ → calcineurinCalcineurinCalcineurin is a protein phosphatase also known as protein phosphatase 3, PPP3CA, and calcium-dependent serine-threonine phosphatase, and formerly known as protein phosphatase 2B . It activates the T cells of the immune system and can be blocked by drugs...
→ NFATC1NFATC1Nuclear factor of activated T-cells, cytoplasmic 1 is a protein that in humans is encoded by the NFATC1 gene.-Further reading:- External links :... - Gαi or Gαo → PKCα/PLCγ2/PLD1Phospholipase D1Phospholipase D1 is an enzyme that in humans is encoded by the PLD1 gene.-Interactions:Phospholipase D1 has been shown to interact with RALA, BIN1, Amphiphysin, Alpha-synuclein, PEA15, RHOA, Protein kinase N1 and CDC42.-Inhibitors:...
→ mTOR
Rapid dephosphorylation of PKCα causes it to transiently move from the cytoplasm to the area of the Golgi apparatus and peripheral nucleus. Here, it forms a complex with PKCα and PLCγ2 from which downstream mTOR and NFAT signaling is initiated.
The upstream Gαi or Gαo signaling suggests the involvement of a G-protein-coupled receptor (GPCR). A candidate GPCR is under study. Syndecan-1 likely serves as a co-receptor. Binding lacritin may improve its GPCR affinity.
Species
Genomic sequencing assembled by EnsemblEnsembl
Ensembl is a joint scientific project between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute, which was launched in 1999 in response to the imminent completion of the Human Genome Project...
reveals the existence of putative lacritin orthologues in other species including: Dasypus novemcinctus (nine-banded armadillo), Echinops telfairi (lesser hedgehog), Felis silvestris catus (house cat), Macaca mulatta (rhesus macaque or monkey), Myotis lucifugus (little brown bat), Pan troglodytes (chimpanzee), Sorex araneus (common shrew), and Tupaia belangeri (northern tree shrew). PONDR and O-glycosylation patterns are similar.
Tissue
Tissue distribution has been examined in humans and monkeys. Lacritin is most highly expressed in the lacrimal glandLacrimal gland
The lacrimal glands are paired almond-shaped glands, one for each eye, that secrete the aqueous layer of the tear film. They are situated in the upper, outer portion of each orbit, in the lacrimal fossa of the orbit formed by the frontal bone. Inflammation of the lacrimal glands is called...
, moderately in salivary gland
Salivary gland
The salivary glands in mammals are exocrine glands, glands with ducts, that produce saliva. They also secrete amylase, an enzyme that breaks down starch into maltose...
s and slightly in mammary
Mammary gland
A mammary gland is an organ in mammals that produces milk to feed young offspring. Mammals get their name from the word "mammary". In ruminants such as cows, goats, and deer, the mammary glands are contained in their udders...
(cancer but not or rarely normal), and thyroid gland
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
s. The salivary gland
Salivary gland
The salivary glands in mammals are exocrine glands, glands with ducts, that produce saliva. They also secrete amylase, an enzyme that breaks down starch into maltose...
expression can be attributed to a discrete group of unidentified ductal-like cells. Some lacritin was reported in lung bronchoalveolar lavage. In lacrimal gland, polarized lacrimal acinar cells appear to be the most prolific lacritin producers, as evidenced by strong staining of secretory granules in keeping with lacritin release after carbachol stimulation. Carbachol-dependent release involves PKC and calcium signaling. Some lacritin is produced by the meibomian gland
Meibomian gland
The meibomian glands are a special kind of sebaceous gland at the rim of the eyelids inside the tarsal plate, responsible for the supply of meibum, an oily substance that prevents evaporation of the eye's tear film. They prevent tear spillage onto the cheek, trapping tears between the oiled edge...
, and also by epithelial cells of the conjunctiva
Conjunctiva
The conjunctiva covers the sclera and lines the inside of the eyelids. It is composed of rare stratified columnar epithelium.-Function:...
and cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
that together with lacrimal gland comprise much of the lacrimal functional unit (LFU). Viewed collectively, the LFU is the primary source of lacritin in the body, and the eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
the main target.
Some changes have been noted in disease. Dry eye is the most common eye disease. Preliminary studies with small trials suggest that lacritin may be differentially downregulated in dry eye. In climatic droplet keratopathy, N119 appears to be unglycosylated. Also a normal breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
localization reported by some has not been replicated in Unigene
Unigene
Unigene Laboratories is a biopharmaceutical company, engaged in the research and development of peptides for medical purposes. The company was founded in 1980 and is located in New Jersey....
(the 'mammary gland
Mammary gland
A mammary gland is an organ in mammals that produces milk to feed young offspring. Mammals get their name from the word "mammary". In ruminants such as cows, goats, and deer, the mammary glands are contained in their udders...
' hit is for breast cancer) and gene array studies, but some breast cancers appear to display elevated expression or LACRT gene amplification.