Hydrogen alleviates impaired lung epithelial barrier in acute respiratory distress syndrome via inhibiting Drp1-mediated mitochondrial fission through the Trx1 pathway.

Acute respiratory distress syndrome (ARDS) is an acute and severe clinical complication lacking effective therapeutic interventions. The disruption of the lung epithelial barrier plays a crucial role in ARDS pathogenesis. Recent studies have proposed the involvement of abnormal mitochondrial dynamics mediated by dynamin-related protein 1 (Drp1) in the mechanism of impaired epithelial barrier in ARDS. Hydrogen is an anti-oxidative stress molecule that regulates mitochondrial function via multiple signaling pathways. Our previous study confirmed that hydrogen modulated oxidative stress and attenuated acute pulmonary edema in ARDS by upregulating thioredoxin 1 (Trx1) expression, but the exact mechanism remains unclear. This study aimed to investigate the effects of hydrogen on mitochondrial dynamics both in vivo and in vitro. Our study revealed that hydrogen inhibited lipopolysaccharide (LPS)-induced phosphorylation of Drp1 (at Ser616), suppressed Drp1-mediated mitochondrial fission, alleviated epithelial tight junction damage and cell apoptosis, and improved the integrity of the epithelial barrier. This process was associated with the upregulation of Trx1 in lung epithelial tissues of ARDS mice by hydrogen. In addition, hydrogen treatment reduced the production of reactive oxygen species in LPS-induced airway epithelial cells (AECs) and increased the mitochondrial membrane potential, indicating that the mitochondrial dysfunction was restored. Then, the expression of tight junction proteins occludin and zonula occludens 1 was upregulated, and apoptosis in AECs was alleviated. Remarkably, the protective effects of hydrogen on the mitochondrial and epithelial barrier were eliminated after applying the Trx1 inhibitor PX-12. The results showed that hydrogen significantly inhibited the cell apoptosis and the disruption of epithelial tight junctions, maintaining the integrity of the epithelial barrier in mice of ARDS. This might be related to the inhibition of Drp1-mediated mitochondrial fission through the Trx1 pathway. The findings of this study provided a new theoretical basis for the application of hydrogen in the clinical treatment of ARDS.

Bicellular Localization of Tricellular Junctional Protein Angulin-3/ILDR2 Allows Detection of Podocyte Injury.

Podocytes serve as part of the renal filtration unit with slit diaphragms. Although the structure of slit diaphragms between two cells is well characterized, how the tricellular contact of podocytes is organized and how it changes in injured podocytes remains unknown. This study focused on a tricellular junction protein, angulin-3, and its localization in healthy podocytes, in developmental stages, and in pathologic conditions, using a newly established monoclonal antibody. Angulin-3 was confined at tricellular junctions of primordial podocytes, then transiently localized at bicellular junctions as foot process interdigitation developed and the intercellular junctions rearranged into slit diaphragm, and eventually distributed in a sparse punctate pattern on the foot processes of adult podocytes. In the rodent podocyte injury models, angulin-3 showed bicellular localization between the foot processes, and the localization turned from punctate to dashed linear pattern along the effaced foot processes with the progression of podocyte injury. Angulin-3 also accumulated between foot processes in a linear pattern in kidney biopsy samples of human nephrotic syndrome. Additionally, the line length of angulin-3 staining signal correlated with risk of relapse under glucocorticoid therapy in patients with minimal change nephrotic syndrome. This study proposes an image program to score the linearity of the accumulation pattern of angulin-3 to evaluate the relapse risk of patients with minimal change nephrotic syndrome.

Telmisartan loading thermosensitive hydrogel repairs gut epithelial barrier for alleviating inflammatory bowel disease.

Inflammatory bowel disease (IBD) remains a global health concern with a complex and incompletely understood pathogenesis. In the course of IBD development, damage to intestinal epithelial cells and a reduction in the expression of tight junction (TJ) proteins compromise the integrity of the intestinal barrier, exacerbating inflammation. Notably, the renin-angiotensin system and angiotensin II receptor type 1 (AT1R) play a crucial role in regulating the pathological progression including vascular permeability, and immune microenvironment. Thus, Telmisartan (Tel), an AT1R inhibitor, loading thermosensitive hydrogel was constructed to investigate the potential of alleviating inflammatory bowel disease through rectal administration. The constructed hydrogel exhibits an advantageous property of rapid transformation from a solution to a gel state at 37°C, facilitating prolonged drug retention within the gut while mitigating irritation associated with rectal administration. Results indicate that Tel also exhibits a beneficial effect in ameliorating colon shortening, colon wall thickening, cup cell lacking, crypt disappearance, and inflammatory cell infiltration into the mucosa in colitis mice. Moreover, it significantly upregulates the expression of TJ proteins in colonic tissues thereby repairing the intestinal barrier damage and alleviating the ulcerative colitis (UC) disease process. In conclusion, Tel-loaded hydrogel demonstrates substantial promise as a potential treatment modality for IBD.

Cellular junction dynamics and Alzheimer's disease: a comprehensive review.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by progressive neuronal damage and cognitive decline. Recent studies have shed light on the involvement of not only the blood-brain barrier (BBB) dysfunction but also significant alterations in cellular junctions in AD pathogenesis. In this review article, we explore the role of the BBB and cellular junctions in AD pathology, with a specific focus on the hippocampus. The BBB acts as a crucial protective barrier between the bloodstream and the brain, maintaining brain homeostasis and regulating molecular transport. Preservation of BBB integrity relies on various junctions, including gap junctions formed by connexins, tight junctions composed of proteins such as claudins, occludin, and ZO-1, as well as adherence junctions involving molecules like vascular endothelial (VE) cadherin, Nectins, and Nectin-like molecules (Necls). Abnormalities in these junctions and junctional components contribute to impaired neuronal signaling and increased cerebrovascular permeability, which are closely associated with AD advancement. By elucidating the underlying molecular mechanisms governing BBB and cellular junction dysfunctions within the context of AD, this review offers valuable insights into the pathogenesis of AD and identifies potential therapeutic targets for intervention.

Modulation of hepatic cellular tight junctions via coculture with cholangiocytes enables non-destructive bile recovery.

Estimation of the biliary clearance of drugs and their metabolites in humans is crucial for characterizing hepatobiliary disposition and potential drug-drug interactions. Sandwich-cultured hepatocytes, while useful for in vitro bile analysis, require cell destruction for bile recovery, limiting long-term or repeated dose drug effect evaluations. To overcome this limitation, we investigated the feasibility of coculturing a human hepatic carcinoma cell line (HepG2-NIAS cells) and a human cholangiocarcinoma cell line (TFK-1 cells) using the collagen vitrigel membrane in a variety of coculture configurations. The coculture configuration with physiological bile flow increased the permeability of fluorescein-labeled bile acids (CLF) across the HepG2-NIAS cell layer by approximately 1.2-fold compared to the HepG2-NIAS monoculture. This enhancement was caused by paracellular leakage due to the loosened tight junctions of HepG2-NIAS, confirmed by the use of an inhibitor for bile acid transporters, the increase of permeability of dextran, and the decrease of the transepithelial electrical resistance (TEER) value. Based on the results of loosening hepatic tight junctions via coculture with TFK-1 in the CLF permeability assay, we next attempted to collect the CLF accumulated in the bile canaliculi of HepG2-NIAS. The recovery of the CLF accumulated in the bile canaliculi was increased 1.4 times without disrupting hepatic tight junctions by the coculture of HepG2-NIAS cells and TFK-1 cells compared to the monoculture of HepG2-NIAS cells. This non-destructive bile recovery has the potential as a tool for estimating the biliary metabolite and provides valuable insights to improve in vitro bile analysis.

Tight junction proteins and biliary diseases.

PURPOSE OF REVIEW: In the pathophysiological context of cholangiopathies and more broadly of hepatopathies, while it is conceptually clear that the maintenance of inter-cholangiocyte and inter-hepatocyte tight junction integrity would be crucial for liver protection, only scarce studies have been devoted to this topic. Indeed, in the liver, alteration of tight junctions, the intercellular adhesion complexes that control paracellular permeability would result in leaky bile ducts and bile canaliculi, allowing bile reflux towards hepatic parenchyma, contributing to injury during the disease process. RECENT FINDINGS: Last decades have provided a great deal of information regarding both tight junction structural organization and signaling pathways related to tight junctions, providing clues about potential intervention to modulate paracellular permeability during cholangiopathies pathogenesis. Interestingly, several liver diseases have been reported to be associated with abnormal expression of one or several tight junction proteins. However, the question remains unanswered if these alterations would be primarily involved in the disease pathogenesis or if they would occur secondarily in the pathological course. SUMMARY: In this review, we provide an overview of tight junction disruptions described in various biliary diseases that should pave the way for defining new therapeutic targets in this field.

The role and mechanism of tight junctions in the regulation of salivary gland secretion.

Tight junctions (TJs) are cell-cell interactions that localize at the most apical portion of epithelial/endothelial cells. One of the predominant functions of TJs is to regulate material transport through paracellular pathway, which serves as a selective barrier. In recent years, the expression and function of TJs in salivary glands has attracted great interest. The characteristics of multiple salivary gland TJ proteins have been identified. During salivation, the activation of muscarinic acetylcholine receptor and transient receptor potential vanilloid subtype 1, as well as other stimuli, promote the opening of acinar TJs by inducing internalization of TJs, thereby contributing to increased paracellular permeability. Besides, endothelial TJs are also redistributed with leakage of blood vessels in cholinergic-stimulated submandibular glands. Furthermore, under pathological conditions, such as Sjögren's syndrome, diabetes mellitus, immunoglobulin G4-related sialadenitis, and autotransplantation, the integrity and barrier function of TJ complex are impaired and may contribute to hyposalivation. Moreover, in submandibular glands of Sjögren's syndrome mouse model and patients, the endothelial barrier is disrupted and involved in hyposecretion and lymphocytic infiltration. These findings enrich our understanding of the secretory mechanisms that link the importance of epithelial and endothelial TJ functions to salivation under both physiological and pathophysiological conditions.

Trichinella spiralis cathepsin L damages the tight junctions of intestinal epithelial cells and mediates larval invasion.

BACKGROUND: Cathepsin L, a lysosomal enzyme, participates in diverse physiological processes. Recombinant Trichinella spiralis cathepsin L domains (rTsCatL2) exhibited natural cysteine protease activity and hydrolyzed host immunoglobulin and extracellular matrix proteins in vitro, but its functions in larval invasion are unknown. The aim of this study was to explore its functions in T. spiralis invasion of the host's intestinal epithelial cells. METHODOLOGY/PRINCIPAL FINDINGS: RNAi significantly suppressed the expression of TsCatL mRNA and protein with TsCatL specific siRNA-302. T. spiralis larval invasion of Caco-2 cells was reduced by 39.87% and 38.36%, respectively, when anti-TsCatL2 serum and siRNA-302 were used. Mice challenged with siRNA-302-treated muscle larvae (ML) exhibited a substantial reduction in intestinal infective larvae, adult worm, and ML burden compared to the PBS group, with reductions of 44.37%, 47.57%, and 57.06%, respectively. The development and fecundity of the females from the mice infected with siRNA-302-treated ML was significantly inhibited. After incubation of rTsCatL2 with Caco-2 cells, immunofluorescence test showed that the rTsCatL2 gradually entered into the cells, altered the localization of cellular tight junction proteins (claudin 1, occludin and zo-1), adhesion junction protein (e-cadherin) and extracellular matrix protein (laminin), and intercellular junctions were lost. Western blot showed a 58.65% reduction in claudin 1 expression in Caco-2 cells treated with rTsCatL2. Co-IP showed that rTsCatL2 interacted with laminin and collagen I but not with claudin 1, e-cadherin, occludin and fibronectin in Caco-2 cells. Moreover, rTsCatL2 disrupted the intestinal epithelial barrier by inducing cellular autophagy. CONCLUSIONS: rTsCatL2 disrupts the intestinal epithelial barrier and facilitates T. spiralis larval invasion.

Finding the junction between claudins and endometrial carcinoma.

Endometrial carcinoma (EC) defines a heterogeneous group of neoplastic diseases originating from the transformation of endometrial cells that constitute the internal lining of the uterus. To date several molecular targets have been analysed to describe the natural course of the disease, claudins being among these. Claudins are the main components of tight junctions (TJs), and their main functions are ascribed to the compartmentalization of tissues and cell-cell communication by means of intracellular ions diffusion: these features are typical of epithelial cells. Their overexpression, mis-localization or loss contribute to the malignancy of EC cells. This review collected all available data regarding the expression, regulation and claudin-related signaling pathways to provide a comprehensive view on the influence of claudin in EC progression. Further, the translational potential of claudin differential expression was explored, indicating that their role in personalized medicine could also contribute to EC therapy besides their employment for diagnosis and prognosis.

Activation of Lysosomal Function Ameliorates Amyloid-ß-Induced Tight Junction Disruption in the Retinal Pigment Epithelium.

Accumulation of pathogenic amyloid-ß disrupts the tight junction of retinal pigment epithelium (RPE), one of its senescence-like structural alterations. In the clearance of amyloid-ß, the autophagy-lysosome pathway plays the crucial role. In this context, mammalian target of rapamycin (mTOR) inhibits the process of autophagy and lysosomal degradation, acting as a potential therapeutic target for age-associated disorders. However, efficacy of targeting mTOR to treat age-related macular degeneration remains largely elusive. Here, we validated the therapeutic efficacy of the mTOR inhibitors, Torin and PP242, in clearing amyloid-ß by inducing the autophagy-lysosome pathway in a mouse model with pathogenic amyloid-ß with tight junction disruption of RPE, which is evident in dry age-related macular degeneration. High concentration of amyloid-ß oligomers induced autophagy-lysosome pathway impairment accompanied by the accumulation of p62 and decreased lysosomal activity in RPE cells. However, Torin and PP242 treatment restored the lysosomal activity via activation of LAMP2 and facilitated the clearance of amyloid-ß in vitro and in vivo. Furthermore, clearance of amyloid-ß by Torin and PP242 ameliorated the tight junction disruption of RPE in vivo. Overall, our findings suggest mTOR inhibition as a new therapeutic strategy for the restoration of tight junctions in age-related macular degeneration.

TRIP6 disrupts tight junctions to promote metastasis and drug resistance and is a therapeutic target in colorectal cancer.

Metastasis is the primary cause of death in colorectal cancer (CRC). Thyroid hormone receptor interacting protein 6 (TRIP6) is an adaptor protein that regulates cell motility. Here, we aim to elucidate the role of TRIP6 in driving CRC tumorigenesis and metastasis and evaluate its potential as a therapeutic target. TRIP6 mRNA is up-regulated in CRC compared to adjacent normal tissues in three independent cohorts (all P < 0.0001), especially in liver metastases (P < 0.001). High TRIP6 expression predicts poor prognosis of CRC patients in our cohort (P = 0.01) and TCGA cohort (P = 0.02). Colon-specific TRIP6 overexpression (Trip6KIVillin-Cre) in mice accelerated azoxymethane (AOM)-induced CRC (P < 0.05) and submucosal invasion (P < 0.0001). In contrast, TRIP6 knockout (Trip6+/- mice) slowed tumorigenesis (P < 0.05). Consistently, TRIP6 overexpression in CRC cells promoted epithelial-mesenchymal transition (EMT), cell migration/invasion in vitro, and metastases in vivo (all P < 0.05), whereas knockdown of TRIP6 exerted opposite phenotypes. Mechanistically, TRIP6 interacted PDZ domain-containing proteins such as PARD3 to impair tight junctions, evidenced by decreased tight junction markers and gut permeability dysfunction, inhibit PTEN, and activate oncogenic Akt signaling. TRIP6-induced pro-metastatic phenotypes and Akt activation depends on PARD3. Targeting TRIP6 by VNP-encapsulated TRIP6-siRNA synergized with Oxaliplatin and 5-Fluorouracil to suppress CRC liver metastases. In conclusion, TRIP6 promotes CRC metastasis by directly interacting with PARD3 to disrupt tight junctions and activating Akt signaling. Targeting of TRIP6 in combination with chemotherapy is a promising strategy for the treatment of metastatic CRC.

Intestinal Barrier Dysfunction in Inflammatory Bowel Disease: Underpinning Pathogenesis and Therapeutics.

The intestinal barrier is composed of several essential elements including luminal enzymes, bile acids, water layer, epithelial layer, and enterocyte layer. It acts as a dynamic interface between the luminal contents of food, commensal and pathogenic bacteria, and the gastrointestinal tract. The role of barrier dysfunction is of significant research interest in the development and targeted treatment of chronic inflammatory gastrointestinal conditions, such as inflammatory bowel disease. This review aims to examine the role of intestinal barrier dysfunction in the development of inflammatory bowel disease, the pathophysiology of increased barrier permeability in inflammatory bowel disease, and to explore potential treatment targets and clinical applications.

Retinal arterial Aß40 deposition is linked with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients.

INTRODUCTION: Vascular amyloid beta (Aß) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients. We tested the hypothesis that the retinal vascular tight junctions (TJs) were compromised and linked to disease status. METHODS: TJ components and Aß expression in capillaries and larger blood vessels were determined in post mortem retinas from 34 MCI or AD patients and 27 cognitively normal controls and correlated with neuropathology. RESULTS: Severe decreases in retinal vascular zonula occludens-1 (ZO-1) and claudin-5 correlating with abundant arteriolar Aß40 deposition were identified in MCI and AD patients. Retinal claudin-5 deficiency was closely associated with cerebral amyloid angiopathy, whereas ZO-1 defects correlated with cerebral pathology and cognitive deficits. DISCUSSION: We uncovered deficiencies in blood-retinal barrier markers for potential retinal imaging targets of AD screening and monitoring. Intense retinal arteriolar Aß40 deposition suggests a common pathogenic mechanism of failed Aß clearance via intramural periarterial drainage.

Mycobacterium abscessus infection results in decrease of oxidative metabolism of lung airways cells and relaxation of the epithelial mucosal tight junctions.

Mycobacterium abscessus complex is a group of environmental pathogens that recently have been isolated more from patients with underlying lung diseases, such and COPD, bronchiectasis, and cystic fibrosis. The mechanisms involved in the pathogenesis of these diseases have only recently been investigated. Infection is associated with biofilm formation on the airway mucosa, invasion of the mucosal epithelial cells and a time-dependent impairment of the integrity of the monolayer. Using electron microscopy, it was shown that Mycobacterium abscessus induced lesions of the cell surface structures. Tight junction proteins claudin-1 and occludin-1 have increased transcription in cells exposed to Mycobacterium abscessus, in contrast to cells exposed to Mycobacterium avium. Infection of A549 alveolar epithelial cells by Mycobacterium abscessus reduced the oxidative metabolism of the cell, without inducing necrosis. A transposon library screen identified mutants that do not alter the metabolism of the A549 cells.Once the bacterium crosses the epithelial barrier, it may encounter sub-epithelial macrophages. Select mutants were used for infection assays to determine their effects on membrane integrity. Translocated select mutants were attenuated in macrophages compared to wild type Mycobacterium abscessus. In summary, the dynamics of Mycobacterium abscessus infection appears to be different from other non-tuberculous mycobacteria (NTMs). Future studies will attempt to address the mechanism involved in airway membrane lesions.

Baicalin Reduces Immune Cell Infiltration by Inhibiting Inflammation and Protecting Tight Junctions in Ischemic Stroke Injury.

Ischemic stroke is a serious health hazard that lacks effective treatment strategies. This study aims to investigate baicalin's effect on tight junctions and immune cell infiltration after ischemic stroke injury. Rat brain microvascular endothelial cells (BMECs) were treated with OGD/R to establish an in vitro model. Caspase-3, Bax, Bcl-2, zonula occludens-1 (ZO-1), occludin, claudin-5, tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-6, inducible nitric oxide synthase (iNOS), Toll-like receptor (TLR) 2, TLR4, and nuclear factor-kappa B (NF-[Formula: see text]B) expressions were detected using qRT-PCR and western blotting. ZO-1, TNF-[Formula: see text], iNOS, IL6, CD31, and ZO-1 expressions were examined using immunofluorescence. A tube formation assay was performed to measure angiogenesis. An ischemia-reperfusion model in rats was established by middle cerebral artery occlusion. The infarct volume was observed using 2,3,5-triphenyltetrazolium chloride staining. TNF-[Formula: see text], iNOS, and IL6 levels in the serum were tested using ELISA. Flow cytometry was performed to examine immune cell inflammatory infiltration. Baicalin had no significant effect on the proliferation of normal BMECs. Baicalin inhibited apoptosis, protected against tight junction injury, and alleviated the inflammatory response in OGD/R-induced BMECs and IR rats, with the highest dose (25[Formula: see text][Formula: see text]g/mL) exerting a superior effect. Baicalin decreased the neurological function score, infarct volume, and brain water content, relieved brain morphological changes, and inhibited immune cell infiltration in vivo. In conclusion, baicalin could reduce BMECs apoptosis, protect tight junctions, and resist immune cell infiltration, thereby alleviating ischemic stroke. Our findings potentially provide a novel treatment strategy for ischemic stroke.

Targeting endothelial tight junctions to predict and protect thoracic aortic aneurysm and dissection.

AIMS: Whether changes in endothelial tight junctions (TJs) lead to the formation of thoracic aortic aneurysm and dissection (TAAD) and serve as an early indicator and therapeutic target remains elusive. METHODS AND RESULTS: Single-cell RNA sequencing analysis showed aberrant endothelial TJ expressions in the thoracic aortas of patients with TAAD. In a ß-aminopropionitrile (BAPN)-induced TAAD mouse model, endothelial TJ function was disrupted in the thoracic aortas at an early stage (5 and 10 days) as observed by a vascular permeability assay, while the intercellular distribution of crucial TJ components was significantly decreased by en face staining. For the non-invasive detection of endothelial TJ function, two dextrans of molecular weights 4 and 70 kDa were conjugated with the magnetic resonance imaging (MRI) contrast agent Gd-DOTA to synthesize FITC-dextran-DOTA-Gd and rhodamine B-dextran-DOTA-Gd. MRI images showed that both probes accumulated in the thoracic aortas of the BAPN-fed mice. Particularly, the mice with increased accumulated signals from 5 to 10 days developed TAAD at 14 days, whereas the mice with similar signals between the two time points did not. Furthermore, the protease-activated receptor 2 inhibitor AT-1001, which seals TJs, alleviated the BAPN-induced impairment of endothelial TJ function and expression and subsequently reduced TAAD incidence. Notably, endothelial-targeted ZO-1 conditional knockout increased TAAD incidence. Mechanistically, vascular inflammation and edema were observed in the thoracic aortas of the BAPN-fed mice, whereas these phenomena were attenuated by AT-1001. CONCLUSION: The disruption of endothelial TJ function is an early event prior to TAAD formation, herein serving as a potential indicator and a promising target for TAAD.

The role of mir-197-3p in regulating the tight junction permeability of celiac disease patients under gluten free diet.

BACKGROUND: Celiac disease (CD) is a hereditary immune-mediated disorder, which is along with the enormous production of pro-inflammatory cytokines and the reduced level of tight junction proteins. The aim of this study was to determine the expression of TNF-α, IFN-γ, IL-18, Occludin, miR-122-5p and miR-197-3p genes in duodenal biopsies of treated CD patients in comparison to the controls. METHODS AND RESULTS: Biopsy specimens were taken from the duodenum of 50 treated CD patients (36 (72%) females and 14 (28%) males with mean age of 37.06 ± 7.02 years) and 50 healthy controls (17 (34%) females and 33 (66%) males with mean age of 34.12 ± 4.9). Total RNA was isolated, cDNA was synthesized and mRNA expression of TNF-α, IFN-γ, IL-18, Occludin, miR-122-5p and miR-197-3p were quantified by relative qPCR using B2M and U6 as internal control genes. All data were evaluated using SPSS (V.21) and GraphPad Prism (V.5). Our results showed that there was no significant difference between patients and controls for intestinal mRNA expression of TNF-α, IFN-γ, IL-18, Occludin, and miR-122-5p (p > 0.05) and the expression of miR-197-3p was significantly increased in CD patients relative to control subjects (p = 0.049). CONCLUSION: This study suggests that adherence to GFD may have a positive effect on the tight junction (TJ) permeability and in this process, miR-197-3p plays an important role. Increased expression of miR-197-3p with a final protective effect on Occludin expression can be further studied as a complement therapeutic target for Celiac disease.

[Advances of tight junction damage in the corneal epithelial barrier in the pathogenesis of corneal diseases].

The cornea is a transparent tissue with significant refractive and barrier functions. Corneal epithelium constitutes the first line of defense against foreign pathogens. Corneal epithelial cells interact to form a functionally selective permeability barrier. Dysfunction of this barrier leads to corneal impairment followed by a series of ocular surface diseases and even blindness. Tight junctions (TJ), located at the top of the intercellular space of corneal epithelial superficial cells, play a critical role in establishing and maintaining the barrier function. Previous studies have shown that destruction of the TJ acts as a crucial step of the occurrence and progression of multiple ocular surface diseases. Understanding the fundamental features and functions of the TJ, noticing the risk factors of TJ disruption, and clarifying the key role of TJ in the pathogenesis of various ocular surface diseases will help to better understand and treat ocular surface diseases.