ArticleThe Journal of biological chemistry
Lacritin proteoforms prevent tear film collapse and maintain epithelial homeostasis.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06854393 (Lacripep, a Novel Investigational Agent, for Corneal Wound Healing and Ocular Surface Homeostasis), which is not on this map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Lacripep, a Novel Investigational Agent, for Corneal Wound Healing and Ocular Surface Homeostasis
Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Site-specific O-glycans influence lacritin structure and multimerization in tears.Protein science : a publication of the Protein Society · 2026Article
- Distinctive Lacritin Cleavage-Potentiated Bactericidal Alteration of thebioRxiv : the preprint server for biology · 2026Article
- Article
- Mapping galectin-3 ligands in human tear fluid establishes spliceoform-dependent lacritin binding.Communications biology · 2026Article
- Advances in Pharmacotherapy and Physiotherapy for Dry Eye Disease: Molecular Mechanisms and Future Directions-A Narrative Literature Review.International journal of molecular sciences · 2026Review
- Translating Biomarker Discovery: From Bench to Bedside in Dry Eye Disease.International journal of molecular sciences · 2025Review
- In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms.The Journal of biological chemistry · 2025Article
- In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms.bioRxiv : the preprint server for biology · 2025Article
- Lacritin cleavage-potentiated targeting of iron - respiratory reciprocity promotes bacterial death.The Journal of biological chemistry · 2025Article
- Targeting Iron - Respiratory Reciprocity Promotes Bacterial Death.bioRxiv : the preprint server for biology · 2024Article
- Sources of Variance in Human Tear Proteomic Samples: Statistical Evaluation, Quality Control, Normalization, and Biological Insight.International journal of molecular sciences · 2024Article
- Tolerability of Current Treatments for Dry Eye Disease: A Review of Approved and Investigational Therapies.Clinical ophthalmology (Auckland, N.Z.) · 2024Review
- Autophagy in dry eye disease: Therapeutic implications of autophagy modulators on the ocular surface.Indian journal of ophthalmology · 2023Review
- Lectin-Based Affinity Enrichment and Characterization of N-Glycoproteins from Human Tear Film by Mass Spectrometry.Molecules (Basel, Switzerland) · 2023Article
- AUTOPHAGY IN THE EYE: FROM PHYSIOLOGY TO PATHOPHYSOLOGY.Autophagy reports · 2023Article
- Autophagy in the normal and diseased cornea.Experimental eye research · 2022Review
- A synthetic tear protein resolves dry eye through promoting corneal nerve regeneration.Cell reports · 2022Article
- Human meibum and tear film derived cholesteryl and wax esters in meibomian gland dysfunction and tear film structure.The ocular surface · 2022Article
- Review
- A spectroscopic approach to measuring meibum lipid composition and conformation in donors with Sjӧgren's syndrome.Experimental eye research · 2021Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
Lipids in complex, protein-enriched films at air/liquid interfaces reduce surface tension. In the absence of this benefit, the light refracting and immunoprotective tear film on eyes would collapse. Premature collapse, coupled with chronic inflammation compromising visual acuity, is a hallmark of dry eye disease affecting 7 to 10% of individuals worldwide. Although collapse seems independent of mutation (unlike newborn lung alveoli), selective proteome and possible lipidome changes have been noted. These include elevated tissue transglutaminase and consequent inactivation through C-terminal cross-linking of the tear mitogen lacritin, leading to significant loss of lacritin monomer. Lacritin monomer restores homeostasis via autophagy and mitochondrial fusion and promotes basal tearing. Here, we discover that lacritin monomer C-terminal processing, inclusive of cysteine, serine, and metalloproteinase activity, generates cationic amphipathic α-helical proteoforms. Such proteoforms (using synthetic peptide surrogates) act like alveolar surfactant proteins to rapidly bind and stabilize the tear lipid layer. Immunodepletion of C- but not N-terminal proteoforms nor intact lacritin, from normal human tears promotes loss of stability akin to human dry eye tears. Stability of these and dry eye tears is rescuable with C- but not N-terminal proteoforms. Repeated topical application in rabbits reveals a proteoform turnover time of 7 to 33 h with gradual loss from human tear lipid that retains bioactivity without further processing. Thus, the processed C-terminus of lacritin that is deficient or absent in dry eye tears appears to play a key role in preventing tear film collapse and as a natural slow release mechanism that restores epithelial homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.