Dry eye disease (DED) is a prevalent ophthalmic ailment with intricate pathogenesis and that occurs primarily due to various factors which affect the ocular surface. DED is characterized by the disruption of tear film homeostasis, inflammatory reaction, and neuroparesthesia. Transient receptor potential vanilloid 1 (TRPV1) is a versatile receptor that can be stimulated by heat, acid, capsaicin (CAP), hyperosmolarity, and numerous inflammatory agents. There is accumulating evidence that implicates TRPV1 in the initiation and progression of DED through its detection of hypertonic conditions and modulation of inflammatory pathways. In this article, we present a comprehensive review of the expression and function of the TRPV1 channel in tissues and cells associated with DED. In addition, we outline the potential mechanisms that implicate TRPV1 in the pathophysiology of DED. The aim of this review is to establish a theoretical basis for TRPV1 as a possible therapeutic target in DED, thereby encouraging further investigations into its role in DED.

BACKGROUND: Modified Danzhi Xiaoyao Powder (MDXP) is a traditional Chinese medicine formula remedy for treating Dry Eye Disease (DED). It showed the function of dispersing stagnated liver Qi for relieving Qi stagnation and clearing heat, which can be effective in treating conditions such as Dry Eye Disease (DED) and irregular menstruation due to liver depression and fire transformation.
OBJECTIVE: This study investigated the mechanism of the effect of MDXP in mice with DED.
METHODS: A DED model was induced in mice using chronic painful stimulation (tail clamping) in combination with Benzalkonium Chloride Solution drops administered in a dry box for 28 days. After modeling, the MDXP groups were given Chinese medicine with different dosages by gavage for 14 days. The following parameters were recorded in each group: body mass, anal temperature, tear secretion, tear film rupture time, and corneal fluorescein staining. Behavioral changes were evaluated by elevating cross-maze and open-field experiments. The levels of inflammatory factors serum tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), fcγR-mediated phagocytosis pathway cell division control protein 42 homolog (CDC42), actin-related protein 2/3 complex subunit 2 (ARPC2), and actin-related protein 3 (ACTR3) were measured by using Enzyme-linked immunoassay (ELISA), immunohistochemical staining, and real-time fluorescent qualitative polymerase chain reaction (RT-qPCR).
RESULTS: MDXP increased body mass and lowered body temperature, prolonged tear film break-up time, promoted tear secretion, repaired corneal damage, decreased horizontal and vertical scores, elevated percentage of open arm times and boom opening time percentage, and reduced the expression levels of inflammatory factors of TNF-α, IL-1β and pathway-related proteins CDC42, ARPC2, and ACTR3 in mice. MDXP also reduced the expression levels of inflammatory factors of TNF-α and IL-1β in human corneal endothelial cells (HCECs), mouse mononuclear macrophage cells (RAW264.7), and human myeloid leukemia mononuclear cells (THP-1).
CONCLUSIONS: MDXP can relieve tension and anxiety, inhibit apoptosis, reduce phagocytosis, reduce the expression of pro-inflammatory factors, repair corneal damage, and improve the symptoms in DED mice. The mechanism of action may be through the fcγR-mediated phagocytosis pathway.

Following viral infection, the innate immune system senses viral products, such as viral nucleic acids, to activate innate defence pathways, leading to inflammation and apoptosis, control of cell proliferation, and consequently, threat to the whole body. The ocular surface is exposed to the external environment and extremely vulnerable to viral infection. Several studies have revealed that viral infection can induce inflammation of the ocular surface and reduce tear secretion of the lacrimal gland (LG), consequently triggering ocular morphological and functional changes and resulting in dry eye disease (DED). Understanding the mechanisms of DED caused by viral infection and its potential therapeutic strategies are crucial for clinical interventional advances in DED. This review summarizes the roles of viral infection in the pathogenesis of DED, applicable diagnostic and therapeutic strategies, and potential regions of future studies.

UNASSIGNED: To investigate binocular dynamic visual acuity (DVA) for patients with dry eye disease (DED).
UNASSIGNED: The prospective study included DED patients. The binocular DVA at 40 and 80 degrees per second (dps), Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), tear film break-up time first (TBUTF), corneal fluorescein staining (CFS), eyelid margin abnormalities and meibomian gland (MG) abnormalities morphology and function were evaluated. A deep learning model was applied to quantify the MG area proportion. The correlation between DVA and DED parameters was analyzed.
UNASSIGNED: A total of 73 DED patients were enrolled. The age, OSDI, CFS, MG expressibility, secretion quality, and eyelid margin abnormalities were significantly positively correlated with the DVA for 40 and 80 dps (all P < 0.05). The MG area proportion in the upper eyelid was negatively correlated with DVA at 40 dps (R = -0.293, P < 0.001) and at 80 dps (R = -0.304, P < 0.001). Subgroup analysis by MG grade demonstrated that the DVA of patients with severe MG dropout (<25% of the total area) was significantly worse than other mild and moderate groups, both in 40 and 80 dps (all P < 0.05). The patients with CFS showed worse 40 (P < 0.001) and 80 dps (P < 0.001) DVA than the patients without CFS.
UNASSIGNED: Binocular DVA is significantly associated with DED symptoms and signs. The DED patients with CFS and severe MG dropout and dysfunction have worse DVA.

Our purpose is to demonstrate the changes in cornea nerve parameters and symptoms and signs in dry eye disease (DED) patients after oral vitamin B1 and mecobalamin treatment. In this randomized double-blind controlled trial, DED patients were randomly assigned to either the treatment group (oral vitamin B1 and mecobalamin, artificial tears) or the control group (artificial tears). Corneal nerve parameters via in vivo confocal microscopy (IVCM), DED symptoms, and signs were assessed at baseline and 1 and 3 months post-treatment. In total, 398 eyes from 199 patients were included. In the treatment group, there were significant improvements in corneal nerve length, width, and neuromas, the sign of conjunctival congestion score (CCS), symptoms of dryness, pain, photophobia, blurred vision, total symptom score, and OSDI (OSDI) at 1/3 months post-treatment (all p < 0.05). Patients who received vitamin B1 and mecobalamin showed greater improvement in CCS, dryness scores at 1 month (p < 0.05), corneal fluorescein staining (CFS) (p = 0.012), photophobia (p = 0.032), total symptom scores (p = 0.041), and OSDI (p = 0.029) at 3 months. Greater continuous improvement in CFS (p = 0.045), dryness (p = 0.033), blurred vision (p = 0.031) and total symptom scores (p = 0.023) was demonstrated at 3 months than at 1 month post-treatment in the treatment group. We found that oral vitamin B1 and mecobalamin can improve corneal nerve length, width, reflectivity and the number of neuromas in IVCM, thereby repairing epithelial cells and alleviating some ocular symptoms. Thus, vitamin B1 and mecobalamin are potential treatment options for patients with DED.

OBJECTIVE: Dry eye disease (DED) is a disease with tear film instability because of multiple factors. This study was conducted to explore roles of occludin and MUC5AC in tear film instability in DED rat model.
METHODS: A total of 20 SD rats were divided into DED group (n = 10) and normal control (NC) group (n = 10). DED rat model was established by subcutaneously injecting with scopolamine hydrobromide. Clinical examinations, including tear breakup time (tBUT), Schirmer\'s test and corneal fluorescein staining, were conducted to determine corneal functions. Transmission electron microscopy was used to measure the ultrastructures of corneal epithelial cells. Western blotting assay was used to identify occludin expression in corneal tissues of DED rats. Real-time PCR (RT-PCR) was performed to verify gene transcription of occludin and MUC5AC. Colocalization between occludin and MUC5AC was identified with confocal fluorescence microscopy.
RESULTS: Tear breakup time was significantly shorter, and corneal fluorescein staining score was predominantly higher in DED rats compared to those in normal rats (P < 0.05). Normal rats showed a steady tear secretion throughout the whole experiments, while DED rats showed a dramatic reduction on day 14. DED rats demonstrated ultrastructural damage of Golgi apparatus and endoplasmic reticulum in corneal epithelial cells. Occludin and MUC5AC expressions were significantly downregulated in corneal tissue of DED rats compared with those of normal rats (P < 0.05). Percentage of occludin-MUC5AC-colocalized corneal epithelial cells in DED rats was significantly less compared with those in normal rats (P < 0.01).
CONCLUSIONS: Tear film stability was damaged in scopolamine-induced DED rats because of the weakened colocalization between occludin and MUC5AC molecule. This study would provide a potential clue for the pathogenesis and a promising theoretical basis for clinical work of DED.

This study aimed to investigate the association of between previously neglected oval cells located in the corneal vortex and dry eye disease (DED). This was an observational, prospective study involving 168 patients with different degrees of DED. In vivo confocal microscopy was used to observe the corneal subbasal nerves and Langerhans cells (LCs) in the corneal vortex and periphery. Bright and oval cells were also observed in the corneal vortex. An artificial intelligence technique was used to generate subbasal nerve fiber parameters. The patients were divided into the three groups based on the presence of inflammatory cells. Group 2 patients showed a significant increase in the corneal peripheral nerve maximum length and average corneal peripheral nerve density. Patients in group 3 had more LCs than other patients. A bright and oval cell was identified in the corneal vortex, which might be a type of immature LC related to the disease severity of DED.

Dry eye disease (DED) is a multifactorial ocular disorder that interferes with daily living and reduces quality of life. However, there is no most ideal therapeutic treatment to address all the deleterious defects of DED. The purpose of this study was to investigate the ability of recombinant human thymosin β4 (rhTβ4) to promote healing in a benzalkonium chloride (BAC)-induced mice DED model and the anti-inflammatory effects involved in that process. Eye drops consisting of 0.05% and 0.1% rhTβ4 were used for treatment of DED. Tear volume and corneal staining scores were measured after 7 days. Periodic acid-Schiff staining for gobleT cells in conjunctiva, immunohistochemical staining for CD4+ T cells, TUNEL assay for apoptotic positive cells in cornea and conjunctiva, qRT-PCR and ELISA assays for multiple cytokines were performed. All clinical parameters showed improvement in both the 0.05% and 0.1% rhTβ4 groups. Specifically, topical application of rhTβ4 significantly increased conjunctival gobleT cells and reduced apoptotic cells in conjunctiva. Mechanically, the rhTβ4 groups showed significantly reduced inflammatory cytokine levels and CD4+ T cells in conjunctiva by blocking NF-κB (nuclear factor kappa B) activation, suggesting that 0.05-0.1% rhTβ4 eye drops may be used as a potential therapeutic treatment for DED.

Purpose: To elucidate the expression profile and the potential role of long non-coding ribonucleic acids (RNAs) (lncRNAs) in a dry eye disease (DED) model. Methods: A DED model was established in C57BL/6J mice with 0.2% benzalkonium chloride (BAC) twice a day for 14 days. The differentially expressed lncRNAs were detected by RNA-seq technology (Gene Expression Omnibus, GEO GSE186450) and the aberrantly expressed lncRNAs were further verified by RT-qPCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to predicate the related candidate genes and potential pathological pathways. Cells from a human corneal epithelial cell line (HCECs) were cultured under hyperosmolarity. The regulation of inflammatory factors by silencing potential targeted lncRNAs was verified in vitro in HCECs. Results: In our study, a significant increase in corneal fluorescence staining and a reduction in tear production were observed in DED mice at all follow-ups compared with the controls, and the differences were increasing over time. In total, 2,649 upregulated and 704 downregulated lncRNAs were identified in DED mice. We selected six aberrantly expressed and most abundant lncRNAs and performed RT-qPCR using the samples for RNA-seq. Chrnb2, Gabarapl2, and Usp31 were thereby confirmed as the most significantly altered lncRNAs. Pathway analysis revealed that the neuroactive ligand-receptor interaction signaling pathway was the most enriched, followed by the calcium signaling pathway and cytokine-cytokine receptor interaction. Following treatment of Gabarapl2 siRNA and Chrnb2 siRNA, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were significantly downregulated in the HCECs. Conclusion: Our study suggests that Chrnb2 and Gabarapl2 may be involved in the inflammation response by regulating TNF-α, IL-1β, and IL-6 in DED. These candidate lncRNAs may be both potential biomarkers and therapeutic targets for DED.

BACKGROUND: To evaluate the clinical efficiency of the treatment of dry eye disease (DED) with ocular pain using deproteinized calf blood extract (DCBE) eye drops as compared to 0.3% sodium hyaluronate (SH) eye drops.
METHODS: This prospective, single-center, masked (double-blind), randomized controlled study included 53 patients divided into two groups: DCBE (n=22) and SH (n=31) group. The DCBE group received DCBE eye drops for 4 weeks, and the SH group received 0.3% SH eye drops for 4 weeks. Corneal fluorescein staining (CFS) scores, tear break up time (TBUT), Schirmer test and the ocular surface disease index (OSDI) scores were evaluated in all patients before treatment, 2 and 4 weeks post-treatment.
RESULTS: The DCBE group showed better improvement in the OSDI light sensitivity scores and ocular pain scores compared with the SH group (P<0.05). At 2 and 4 weeks post-treatment, the DCBE group and the SH group showed significant improvement in TBUT, Schirmer test, CFS, OSDI score, light sensitivity score and ocular pain score (P<0.05) compared with the data from before treatment.
CONCLUSIONS: This study indicates that DCBE eye drops can relieve ocular pain and light sensitivity in dry eye patients better than SH eye drops.