OBJECTIVE

This study compared the proportion of dry eye disease (DED) diagnosed using the Philippine criteria with that diagnosed using the Asia Dry Eye Society (ADES) criteria among participants, and characterized DED features using clinical tests and the OCULUS Keratograph® 5M (K5M; OCULUS Optikgeräte GmbH, Wetzlar, Germany).

This multicenter, cross-sectional study included participants with and without DED. Participants completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent fluorescein tear breakup time (FTBUT) measurement, fluorescein staining of the cornea, lissamine green staining of the conjunctiva, Schirmer 1 test without anesthesia, and basal tear secretion test (BST). The OCULUS K5M was used to measure noninvasive tear breakup time (NIKBUT) and tear meniscus height (TMH), and to perform meibography.

The analysis included 344 eyes from 172 patients with DED and 44 eyes from 22 normal participants. Patients with DED were mostly female (66.3%). Compared to normal participants, patients with DED were older (42.7 ± 14.6 years) and had higher OSDI scores (28.6 ± 21.0). Among those diagnosed with DED using the Philippine criteria, 53.2% met the ADES criteria. Evaporative DED was the predominant type (53.2%). DED eyes had lower FTBUT (5.0 ± 3.3 seconds) and NIKBUT (12.3 ± 5.9 seconds) than controls (p CONCLUSION

There were disparities between the Philippine and ADES criteria for DED diagnosis and differences in tear measurements using clinical tests and the OCULUS Keratograph, indicating the need to harmonize diagnostic standards.

OBJECTIVE: To compare the clinical efficacy between penetrating needling of three eye acupoints combined with sodium hyaluronate eye drops and sodium hyaluronate eye drops alone for the treatment of dry eye. METHODS: A total of 156 patients (312 eyes) with dry eye were randomly assigned to an observation group and a control group, with 78 patients (156 eyes) in each group. The control group was treated with sodium hyaluronate eye drops, one drop per eye, four times daily, for 4 weeks. In addition to the sodium hyaluronate treatment, the observation group received penetrating needling of three eye acupoints. Acupoints included bilateral Cuanzhu (BL2), Sizhukong (TE23), Sibai (ST2), and Jingming (BL1). Needling was performed once daily, four times a week, for 4 weeks. The subjective ocular symptom scores, neuropathic pain symptom inventory-eye (NPSI-Eye) scores, ocular surface disease index (OSDI) scores, corneal fluorescein staining (FL) scores, tear break-up time (BUT), SchirmerⅠtest (SⅠT), central tear meniscus height (TMH), and tear levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were evaluated before and after treatment in the two groups. Clinical efficacy was also compared between the two groups. RESULTS: After treatment, both groups showed significant improvements in subjective ocular symptom scores, NPSI-Eye scores, OSDI scores, FL scores, and reductions in tear IL-6 and TNF-α levels (P<0.01). Additionally, BUT, SⅠT, and TMH were increased significantly in both groups (P<0.01). After treatment, the subjective ocular symptom scores, NPSI-Eye score, OSDI score, FL score, and tear levels of IL-6 and TNF-α in the observation group were lower than those in the control group (P<0.01, P<0.05), while BUT, SⅠT, and TMH were significantly improved compared to the control group (P<0.01). The markedly effective rate and total effective rate in the observation group were 83.3% (65/78) and 100.0% (78/78), respectively, which were higher than 52.6% (41/78, P<0.01) and 92.3% (72/78, P<0.05) in the control group. CONCLUSION The penetrating needling of three eye acupoints combined with sodium hyaluronate eye drops can effectively alleviate symptoms of dry eye, reduce inflammatory response, and has superior efficacy to sodium hyaluronate eye drops alone.
Humans ; Hyaluronic Acid/administration & dosage* ; Male ; Female ; Dry Eye Syndromes/genetics* ; Middle Aged ; Acupuncture Points ; Ophthalmic Solutions/administration & dosage* ; Adult ; Aged ; Treatment Outcome ; Acupuncture Therapy ; Interleukin-6/genetics* ; Young Adult ; Tumor Necrosis Factor-alpha/metabolism*

INTRODUCTION: Hydroxychloroquine (HCQ), originally an antimalarial drug, is currently used to treat multiple disorders, especially rheumatic diseases. Given its good efficacy and safety, HCQ is widely administered in pregnant patients. However, the safety profile of HCQ during pregnancy remains controversial due to limited research. In addition, HCQ has been reported to reduce preeclampsia in patients with systemic lupus erythematosus (SLE) and could potentially alleviate the symptom of preeclampsia. However, the clinical profile and molecular mechanism of HCQ in preeclampsia is yet to be fully understood. METHOD: We reviewed the literature on HCQ treatment in pregnancy with rheumatic diseases and preeclamp-sia in PubMed and Web of Science. We also discussed the safety of long-term therapy with HCQ during pregnancy. RESULTS: HCQ mainly modulates autoimmune response through inhibition of lysosomal function, toll-like receptor (TLR) signalling, nicotinamide adenine dinucleotide phosphate-mediated oxidative stress and autophagy. Benefits of HCQ in treating rheumatic diseases, including antiphospholipid syndrome, rheumatoid arthritis and Sjogren's syndrome during pregnancy, has been demonstrated in clinics. In particular, multiple clinical guidelines recommend HCQ as an indispensable therapeutic drug for pregnant patients with SLE. Additionally, it may potentially function in preeclampsia to improve clinical symptoms. CONCLUSION HCQ is effectively used for rheumatic diseases during pregnancy. The benefits of HCQ treatment in rheumatic diseases outweigh the risk of adverse reactions it induces in pregnant women.
Humans ; Hydroxychloroquine/pharmacology* ; Pregnancy ; Female ; Antirheumatic Agents/pharmacology* ; Rheumatic Diseases/drug therapy* ; Pregnancy Complications/drug therapy* ; Pre-Eclampsia/prevention & control* ; Lupus Erythematosus, Systemic/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Antiphospholipid Syndrome/drug therapy* ; Sjogren's Syndrome/drug therapy*

This study investigated the therapeutic effects of Yiguanjian on dry eye in rats and its mechanisms involving the T helper cell 17(Th17)/regulatory T cell(Treg) balance. The rat model of dry eye was established by administrating 0.2% benzalkonium chloride solution in eye drops. After successful modeling, the rats were treated with Yiguanjian for 4 consecutive weeks. The Schirmer test was carried out to assess the lacrimal gland function, corneal fluorescence staining to detect corneal injury, hematoxylin-eosin staining to observe corneal histopathology, enzyme-linked immunosorbent assay to measure serum levels of interleukin(IL)-6, IL-8, IL-17A, IL-21, and tumor necrosis factor-α(TNF-α), RT-qPCR to analyze mRNA levels of retinoic acid receptor-related orphan receptor gamma t(RORγt) and forkhead box protein p3(Foxp3) in the corneal tissue, immunofluorescence double staining to evaluate RORγt and Foxp3 expression in the lacrimal gland tissue, and Western blot to quantify the protein levels of signal transducer and activator of transcription 3(STAT3), phosphorylated STAT3(p-STAT3), Janus kinase 2(Jak2), phosphorylated Jak2(p-Jak2), RORγt, and Foxp3 in the corneal tissue. The results demonstrated that Yiguanjian increased tear secretion(P<0.01), alleviated corneal damage and pathological changes, and lowered the serum levels of IL-6, IL-8, IL-17A, IL-21, and TNF-α(P<0.05) in model rats. Additionally, Yiguanjian decreased the ratio of RORγt to Foxp3 in the corneal and lacrimal gland tissue(P<0.01), downregulated the protein levels of STAT3, Jak2, and RORγt(P<0.05), upregulated the protein level of Foxp3(P<0.05), and inhibited phosphorylation of STAT3 and Jak2(P<0.01). These findings indicate that Yiguanjian ameliorates ocular surface dysfunction in dry eye rats by restoring Th17/Treg balance in the corneal and lacrimal gland tissue and suppressing systemic inflammatory cytokine release, thus mitigating ocular surface inflammation.
Animals ; Rats ; T-Lymphocytes, Regulatory/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Th17 Cells/immunology* ; Male ; Rats, Sprague-Dawley ; Dry Eye Syndromes/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/immunology* ; Lacrimal Apparatus/immunology* ; Humans ; STAT3 Transcription Factor/immunology*

Sjogren's syndrome (SS) is a common autoimmune disorder that primarily targets exocrine glands, leading to hallmark manifestations of xerostomia and xerophthalmia, with potential progression to multisystem involvement. The rapid advances in omics technologies-including metabolomics, proteomics, and transcriptomics-have yielded substantial insights into SS pathophysiology. This review consolidates current evidence on omics-derived biomarkers in SS. Studies consistently implicate aberrant glucose metabolism, neutrophil-derived enzyme activity, mitochondrial bioenergetic impairment, ferroptosis, and apoptotic pathways as central to SS development. These findings refine our understanding of disease mechanisms and the heterogeneity of therapeutic responses. Hydroxyproline has emerged as a candidate marker for distinguishing SS from IgG4-related disease, whereas distinct cytokine and chemokine signatures may enable earlier diagnosis. Genomic analyses demonstrate a robust association between expression of the rs11797 locus and SS-related lymphomagenesis, and several genes controlling DNA methylation represent promising therapeutic targets. Collectively, these findings lay the groundwork for personalized risk stratification and intervention in SS. The review concludes by summarizing existing progress and outlining priorities for future omics-based investigations.
Humans ; Sjogren's Syndrome/diagnosis* ; Biomarkers/analysis* ; Metabolomics/methods* ; Proteomics/methods* ; Genomics ; Multiomics

OBJECTIVE: To investigate the effect of aquaporin 5 (AQP5) on Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor κB (NF-κB) signaling pathway in Sjögren syndrome (SS) rats. METHODS: The SS gene expression data sets GSE406611 and GSE84844 were extracted from the Gene Expression Omnibus (GEO), and the AQP5 mRNA expression was analyzed by R software. The rat SS model was constructed. The successfully modeled rats were divided into SS group, SS+NC group, and SS+pc group, 10 rats in each group; and 10 rats were set as Normal group. The rats in the SS+NC group were injected with 10 μg of rno-pcDNA3.1-AQP5-NC at the submandibular gland, subcutaneously every day for 28 days. The rats in the SS+pc group were injected with 10 μg of rno-pcDNA3.1-AQP5 at the submandibular gland, subcutaneously every day for 28 days. The enzyme-linked immunosorbent assay (ELISA) kit was used to detect the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the serum. High-throughput sequencing was used to identify the target genes. Quantitative real-time PCR (qPCR) and Western blot were used to detect the mRNA and protein expressions of AQP5, TLR4, MyD88, and NF-κB in the rat submandibular gland tissue. RESULTS: In the SS dataset GSE406611 and GSE84844, the mRNA expression of AQP5 in SS was significantly reduced. Compared with the Normal group, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS group were significantly increased, the mRNA and protein expressions of AQP5 were significantly decreased. After overexpression of AQP5, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS+pc group were significantly decreased, the mRNA and protein expressions of AQP5 were significantly increased. The differences were statistically significant (all P < 0.05). CONCLUSION The expression of AQP5 is involved in the progression of SS. Increasing the expression of AQP5 can significantly inhibit inflammatory stress and reduce the pathological damage of submandibular gland tissue. This may be related to the inhibition of TLR4/MyD88/NF-κB conduction.
Animals ; Toll-Like Receptor 4/genetics* ; Myeloid Differentiation Factor 88/genetics* ; Aquaporin 5/metabolism* ; Sjogren's Syndrome/genetics* ; Signal Transduction ; NF-kappa B/metabolism* ; Rats ; Rats, Sprague-Dawley ; Interleukin-1beta/metabolism* ; Female

OBJECTIVES: To investigate the mechanism mediating the regulatory effect of miR-155-5p on proliferation of human submandibular gland epithelial cells (HSGECs) in primary Sjogren's syndrome (pSS). METHODS: Dual luciferase reporter assay was used to verify the targeting relationship between miR-155-5p and the PI3K/AKT pathway. In a HSGEC model of pSS induced by simulation with TRAIL and INF-γ, the effects of miR-155-inhibitor-NC or miR-155 inhibitor on cell viability, cell cycle, apoptosis and proliferation were evaluated using CKK8 assay, flow cytometry and colony formation assay. ELISA and RT-PCR were used to detect the expressions of inflammatory cytokines and miR-155-5p mRNA in the cells; Western blotting was performed to detect the expressions of proteins in the PI3K/AKT signaling pathway. RESULTS: Dual luciferase assay showed that miR-155-5p targets the PI3K/AKT pathway via PIK3R1 mRNA. The HSGEC model of pSS showed significantly decreased cell viability, cell clone formation ability and expressions IL-10 and IL-4 and increased cell apoptosis, cell percentage in G2 phase, expressions of TNF‑α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-Akt/AKT ratio, and PIK3R1 protein expression. Treatment of the cell models with miR-155 inhibitor significantly increased the cell viability, G1 phase cell percentage, colony formation ability, and expressions of IL-10 and IL-4 levels, and obviously reduced cell apoptosis rate, G2 phase cell percentage, expressions of TNF-α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-AKT/AKT ratio, and PIK3R1 protein expression. CONCLUSIONS In HSGEC model of pSS, inhibition of miR-155-5p can promote cell proliferation and reduced cell apoptosis by targeting PI3K1 mRNA to negatively regulate the overexpression of PI3K/AKT signaling pathway.
Humans ; MicroRNAs/genetics* ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Sjogren's Syndrome/pathology* ; Epithelial Cells/cytology* ; Submandibular Gland/cytology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Apoptosis ; Class Ia Phosphatidylinositol 3-Kinase ; Cells, Cultured

Tricellulin, a key tricellular tight junction (TJ) protein, is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands. This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren's syndrome (SS). Employing a multifaceted approach involving patient biopsies, non-obese diabetic (NOD) mice as a SS model, salivary gland acinar cell-specific tricellulin conditional knockout (Tric^CKO) mice, and IFN-γ-stimulated salivary gland epithelial cells, we investigated the role of tricellulin in SS-related hyposalivation. Our data revealed diminished levels of tricellulin in salivary glands of SS patients. Similarly, NOD mice displayed a reduction in tricellulin expression from the onset of the disease, concomitant with hyposecretion and an increase in salivary albumin content. Consistent with these findings, Tric^CKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals. Mechanistically, the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin. Treatment with AT1001, a TJ sealer, ameliorated epithelial barrier dysfunction, restored tricellulin expression, and consequently alleviated hyposalivation in NOD mice. Importantly, treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage. Collectively, we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS. Our findings highlight tricellulin as a potential therapeutic target for hyposecretion, particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.
Sjogren's Syndrome/complications* ; Animals ; Xerostomia/etiology* ; Mice ; Mice, Inbred NOD ; MARVEL Domain Containing 2 Protein/metabolism* ; Humans ; Mice, Knockout ; Disease Models, Animal ; Interferon-gamma ; Salivary Glands/metabolism* ; Tight Junctions/metabolism* ; MicroRNAs/metabolism* ; Female

Sjögren's syndrome (SS) is an autoimmune disease characterized primarily by oral and periocular dryness. Astragalus-Salvia (AS) and Ophiopogon-Dendrobium (OD) represent two frequently utilized herb pairs in SS treatment. While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms, its underlying mechanism remains unclear. This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic (NOD)/Ltj mice with SS. The study utilized NOD/Ltj mice as SS models, administering AS-OD treatment for 10 weeks at doses of 113.1, 226.2, and 339.3 mg·d^-1·20 g^-1. Results demonstrated that AS-OD improved SS symptoms, evidenced by enhanced salivary flow rate, decreased anti-SSA/Ro and anti-SSB/La antibody levels, increased swimming duration, and reduced lactate (LA) and blood urea nitrogen (BUN) levels in NOD/Ltj mice. AS-OD reduced lymphocyte infiltration, enhanced Aquaporin-5 (AQP5) expression in the submandibular gland, decreased inflammatory cytokine levels in the submandibular gland, and reduced the T helper type 17/regulatory T lymphocyte (Th17/Treg) cell ratio in the spleen. Transcriptomic and proteomic analyses indicated AS-OD's involvement in regulating phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and Janus kinase 3/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways, with inhibitory effects validated in both NOD/Ltj mice submandibular gland and A-253 cells. Furthermore, AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway. In A-253 cells, AS-OD reduced inflammatory cytokine levels, CXC chemokine ligand 9/10 (CXCL9/10), and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway. AS-OD mitigates SS by suppressing inflammation and immune responses through the PI3K/AKT and JAK1/STAT3 pathways.
Animals ; STAT3 Transcription Factor/genetics* ; Sjogren's Syndrome/immunology* ; Mice, Inbred NOD ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Janus Kinase 1/genetics* ; Humans ; Female ; Astragalus Plant/chemistry* ; Male

Dry eye disease (DED), currently and, perhaps, at long last a widely accepted prevalent ocular disorder, poses significant challenges, particularly in the developing world, including the Philippines. It disrupts the tear film, leading to discomfort and visual impairment, thereby affecting not only quality of life but economic productivity as well. The ubiquitousness of computer screen use and the evolution of cataract surgery into refractive surgery are only two causative factors of a complex, multivariate problem. Despite its global prevalence, a stark contrast exists in the awareness, diagnosis, and treatment of DED between developed and developing regions. This editorial aims to underscore these disparities, focusing on the crucial roles of healthcare awareness, diagnostic advancements, accessible treatment options, prioritization of governmental policies, and the ethical engagement of the pharmaceutical industry to enhance DED management in under-resourced settings.
Dry Eye Syndromes