Lacrimal Gland Research Articles

Assessment of Vidian canal morphology in axial section and its associated structures using cone beam computed tomography: A descriptive study

The Vidian Nerve (VN), a branch of the trigeminal nerve, passes by the Vidian Canal (VC), located at the base of the skull. The VC branches into the greater petrosal nerve and the VN in the pterygopalatine fossa, where the greater petrosal nerve carries parasympathetic fibers to the lacrimal glands and nasal mucosa, and the VN carries sensory fibers from the nasopharynx, nasal cavity, and palate. In this study, 60 subjects of both sexes who underwent cone beam computed tomography (CBCT) were selected by a convenient sampling technique. The data were subjected to statistical analysis following the examination of the various parameters in the axial sections. Among the various morphological characteristics appraised in the axial section, there was no significant sexual dimorphism, except for the angle between the VC and the medial wall of the maxillary sinus, which shows statistical significance. The present study aims to investigate morphometric analysis and its associated structures, offering insightful information about the complex structure of the Vidian canal (VC), which provides adequate knowledge for surgeons to plan with more caution complex skull base procedures, and eventually to lower the therapeutical risks associated with it.

Lacrimal gland enlargement in thyroid eye disease.

This study aimed to investigate lacrimal gland (LG) enlargement in thyroid eye disease (TED) patients on magnetic resonance imaging (MRI). A retrospective review was conducted on TED patients who had undergone fat-suppressed contrast-enhanced T1-weighted MRI of the orbits. The lacrimal gland was segmented on OsiriX in consecutive axial and coronal slices to determine its volume. Enlargement was defined as a volume greater than 1100mm3, based on previous normative data. Asymmetric enlargement was defined if one side was enlarged but the contralateral side was not. Clinical data including presentation (active/inactive) and presence or absence of dysthyroid optic neuropathy was evaluated. The study population consisted of 88 orbits from forty-four patients with a mean age of 53 ± 15years, with 29 (65%) being female. Twelve patients (27%) had LG enlargement, with eight (18%) having bilateral enlargement and four (9%) having asymmetric enlargement. There was no significant difference in age (p = 0.17) or sex (p = 0.44) between the LG enlarged and non-enlarged groups. There was also no significant difference in the clinical activity (p = 0.46) or prevalence of dysthyroid optic neuropathy (p = 0.63) between the LG enlarged orbits and non-LG enlarged orbits. Lacrimal gland enlargement may be observed in approximately thirty percent of TED patients, with asymmetric enlargement in approximately ten percent of cases.

Morphological aberration of corneal nerves in hyposecretory dry eye guinea pigs.

Dry eye, a common ocular surface disease associated with tear film instability and corneal impairment, is frequently accompanied by ocular discomfort and pain. Recent research has shown that corneal nerve dysfunction may play a role in certain pathologies of dry eye; however, the details remain unclear. To clarify the aberration in corneal nerves underlying sensory abnormalities, in addition to corneal impairment in dry eye, we examined the morphological alterations of nerve fibers in the corneas excised from guinea pigs with dry eye, where the lacrimal glands were surgically excised. Guinea pigs with dry eye exhibited reduced tear volume, increased spontaneous blink frequency, and corneal epithelial damage. Simultaneously, the subbasal nerve plexus in the cornea visualized using an anti-tubulin βIII antibody partially outgrew and became convoluted. The morphology of peptidergic nerves containing calcitonin gene-related peptide, which may function as a polymodal nociceptor, was also altered. These results indicate that guinea pigs with excised lacrimal glands can serve as useful tools for investigating the neuronal mechanisms underlying corneal pathology in dry eyes. Additionally, chronic tear deficiency may considerably alter nerve structure, including peptidergic nerves in the cornea, accompanied by epithelial damage and increased blink frequency.

Advanced Biomaterials for Lacrimal Tissue Engineering: A Review

The lacrimal gland (LG) is vital for ocular health, producing tears that lubricate and protect the eye. Dysfunction of the LG leads to aqueous-deficient dry eye disease (DED), significantly impacting quality of life. Current treatments mainly address symptoms rather than the underlying LG dysfunction, highlighting the need for regenerative therapies. Tissue engineering offers a promising solution, with biomaterials playing crucial roles in scaffolding and supporting cell growth for LG regeneration. This review focuses on recent advances in biomaterials used for tissue engineering of the lacrimal gland. We discuss both natural and synthetic biomaterials that mimic the extracellular matrix and provide structural support for cell proliferation and differentiation. Natural biomaterials, such as Matrigel, decellularized extracellular matrices, chitosan, silk fibroin hydrogels, and human amniotic membrane are evaluated for their biocompatibility and ability to support lacrimal gland cells. Synthetic biomaterials, like polyethersulfone, polyesters, and biodegradable polymers (PLLA and PLGA), are assessed for their mechanical properties and potential to create scaffolds that replicate the complex architecture of the LG. We also explore the integration of growth factors and stem cells with these biomaterials to enhance tissue regeneration. Challenges such as achieving proper vascularization, innervation, and long-term functionality of engineered tissues are discussed. Advances in 3D bioprinting and scaffold fabrication techniques are highlighted as promising avenues to overcome current limitations.

PINK1/Parkin-Mediated Mitophagy Ameliorates Mitochondrial Dysfunction in Lacrimal Gland Acinar Cells During Aging.

Aging alters the function of the lacrimal gland and disrupts the balance of the microenvironment on the ocular surface, eventually leading to aqueous-tear-deficient dry eye. Mitophagy has been reported to play an important role in aging, but the underlying mechanism remains unclear. The young (6 weeks) and middle-aged (12months) male C57BL/6J mice were used in this study, and mitophagy agonist rapamycin and inhibitor Mdivi-1 were used in in vivo experiments. Hematoxylin and eosin, Masson, Oil Red O, and reactive oxygen species (ROS) staining were used to detect histological changes and lipids in lacrimal gland. Changes in the expression of proteins were identified by Western blotting of lacrimal gland lysates. Transmission electron microscopy and immunofluorescence staining were used to assess mitophagy. The single-cell RNA sequencing (scRNA-seq) and bioinformatics analyses were used to detect transcription signature changes during aging. In this study, we discovered that aging increased oxidative stress, which increased apoptosis, and generated ROS in acinar epithelial cells. Furthermore, activation of PINK1/Parkin-mediated mitophagy by rapamycin reduced lacrimal gland ROS concentrations and prevented aging-induced apoptosis of acinar cells, thereby causing histological alterations, microstructural degradation, and increasing tear secretion associated with ROS accumulation. By contrast, Mdivi-1 aggregates mitochondrial function and thereafter leads to lacrimal gland function impairment by inhibiting mitochondrial fission and giving rise to mitophagy. Overall, our findings suggested that aging could impair mitochondrial function of acinar cells, and age-related alterations may be treated with therapeutic approaches that enhance mitophagy while maintaining mitochondrial function.

Clinicopathological features of lacrimal gland biopsy lesions in 582 Chinese patients

Background This study was conducted to assess the clinicopathological characteristics of biopsy lesions in the lacrimal gland, in response to evolving pathological technologies and the emergence of new diseases. A retrospective review of case notes was conducted for 582 patients with biopsied lacrimal gland lesions at West China Hospital of Sichuan University in China. This study, spanning from January 1, 2010, to December 31, 2021, recorded demographics, clinical features, imaging findings, histopathological diagnoses, and recurrence rates. In a cohort of 582 patients, the mean age was 47.5 years, with 318 being female. Bilateral disease was present in 127 patients. Common signs and symptoms included a palpable mass, lid swelling, proptosis, and decreased ocular movements or diplopia. The predominant pathologies identified were inflammation, epithelial tumors, and lymphoproliferative lesions. Patients with inflammation (mean 32.8 months) experienced symptoms for a longer period compared to those with lymphoproliferative lesions (mean 22.2 months) (95% confidence interval [CI] 1.53–19.27, P = 0.022). Younger patients tended to have structural lesions (mean 42.5 years) (95%CI 4.74–21.59, P = 0.003), inflammation (mean 42.9 years) (95%CI 0.46–6.57, P<0.001), or epithelial tumors (mean 46.4 years) (95%CI 6.21–12.38, P<0.001), while older patients more frequently had lymphoproliferative lesions (mean 55.7 years). The period from 2016 to 2021 saw a higher diagnosis rate of biopsied lacrimal gland lesions than from 2010 to 2015. During this later period, there was an increase in cases of immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and malignant epithelial tumors, while lymphoid hyperplasia cases declined. Adenoid cystic carcinoma showed the highest recurrence rate, with lesion extent and Ki-67 index identified as independent risk factors in our study. Inflammation, epithelial tumors, and lymphoproliferative lesions were the three primary causes of lacrimal gland lesions in our study group. Among the inflammatory conditions, IgG4-ROD was the most specific. The incidence of lacrimal gland lesions has risen, particularly for IgG4-ROD. Adenoid cystic carcinoma among the lacrimal gland lesions was prone to recurrence, with the extent of the lesion and Ki-67 index serving as independent risk factors.

In vivo lacrimal gland imaging artefact assessment based on swept-source optical coherence tomography for dry eye disease.

This study aimed to characterise imaging artefacts in the lacrimal gland using swept-source optical coherence tomography (SS-OCT) in patients with dry eye disease (DED) and healthy participants and identify risk factors for these artefacts. In total, 151 eyes, including 104 from patients with DED and 47 from non-DED participants, were analysed. Demographic data collection, comprehensive ocular examinations and SS-OCT imaging of the palpebral lobe of the lacrimal gland were performed. Artefacts were classified into distinct categories with different severities. Univariate and multivariate logistic regression analyses were performed to evaluate the association of age, gender, best-corrected visual acuity, intraocular pressure (IOP) and the presence of DED with the presence of artefacts. Eight artefact types and severity grading were defined by analysing 1208 lacrimal SS-OCT images. The three most prevalent artefacts were defocus (75.83%), cliff (67.47%) and Z-off (58.44%). The presence of artefacts was significantly associated with the presence of DED (OR=9.13; 95% CI, 2.39 to 34.88; p=0.001) and higher IOP (OR=1.34; 95% CI, 1.14 to 1.58; p<0.001). Furthermore, multivariate logistic analyses showed that lower tear film breakup time (OR=0.71; 95% CI, 0.55 to 0.92; p=0.009) and higher meibum quality score (OR=2.86; 95% CI, 1.49 to 5.48; p=0.002) were significantly associated with higher odds for the presence of artefacts. DED eyes had more SS-OCT image artefacts than normal eyes. Stringent standardised image quality control should be implemented before further image analysis when using SS-OCT to assess lacrimal gland image.

A Stratification Approach Based on Salivary Gland Ultrasonography for Assessing Secretory Function in Sjögren's Disease.

Our aim was to develop an ultrasonographic scoring model for staging hypofunction of salivary gland (SG) in patients suffering from Sjögren's disease (SjD). The assessment of SG secretory hypofunction was conducted by measuring whole salivary flows. B-mode ultrasonography was performed bilaterally on the parotid and submandibular glands to evaluate the Gland score and OMERACT score quantitatively. The correlation between these scores and SG secretory function in SjD patients was analyzed, leading to the development of an ultrasonographic scoring model for staging SG hypofunction. A one-center derivation cohort comprising 164 SjD patients and a double-center validation cohort consisting of 107 SjD patients were included. Both ultrasonographic scores demonstrated excellent discriminatory ability between SjD patients with hypofunction and those with normal function (both AUC>0.8, p<0.001). A novel ultrasonographic scoring model revealed that low total OMERACT scores (<5) indicated initial-stage SG hypofunction, while high scores (>9) suggested end-stage hypofunction. Conversely, patients with moderate-level total OMERACT scores (5~9) require further stratification using total Gland scores. The incidence of SG hypofunction among all 271 SjD patients was found to be 18% in the initial stage, 58% in the progressive stage, and 100% in the end stage (p<0.001). Furthermore, the incidence of lacrimal gland involvement and hyperglobulinemia (IgG>16 IU/mL) was significantly lower in the initial-stage patients compared to those at other stages (all p<0.001). The novel ultrasonographic scoring model incorporates precise definitions for each stage, providing a robust and clinically significant approach to stratify salivary gland secretory hypofunction in SjD.

Possible involvement of Toll-like receptor 8-positive monocytes/macrophages in the pathogenesis of Sjögren's disease.

Sjögren's disease (SjD) is an autoimmune disease marked by lymphocytic infiltration of salivary and lacrimal glands, leading to glandular dysfunction, where CD4-positive helper T (Th) cells and their cytokines are crucial in the pathogenesis. Recent studies have demonstrated that Toll-like receptors (TLRs), particularly those recognizing immune complexes containing DNA and RNA, contribute to Th cell activation in various autoimmune diseases. This study explores the expression and function of these TLRs in SjD. DNA microarray analysis of salivary gland tissue from six SjD patients and real-time PCR (n = 32) was used to identify overexpressed TLRs. Single-cell RNA sequencing (scRNA-seq) was performed using tissue lesions and integrated with published scRNA-seq data from tissues and peripheral blood mononuclear cells to examine gene expression in macrophages and monocytes. Finally, multi-color immunofluorescence staining was conducted to confirm TLR8 expression and function in SjD lesions (n = 19). DNA microarray analysis revealed the up-regulation of TLR8, along with other TLRs and innate immune response genes in SjD. Real-time PCR showed significant up-regulation of TLR7 and TLR8. TLR8 up-regulated in both analyses. In scRNA-seq analysis, the TLR8-expressing cluster comprised macrophages and monocytes, which also produced T cell activation genes like CD86. TLR8-positive macrophages infiltrated inflammatory sites and frequently expressed CD86 in quantitative imaging approaches. These results suggest that infiltrating monocytes and macrophages may produce cytokines and chemokines through TLR8 stimulation, potentially enhancing B7 molecule expression, promoting the adaptive immune response, and contributing to SjD pathogenesis.

Screening of pathologically significant diagnostic biomarkers in tears of thyroid eye disease based on bioinformatic analysis and machine learning.

Lacrimal gland enlargement is a common pathological change in patients with thyroid eye disease (TED). Tear fluid has emerged as a new source of diagnostic biomarkers, but tear-based diagnostic biomarkers for TED with high efficacy are still lacking. We aim to investigate genes associated with TED-associated lacrimal gland lesions. Additionally, we seek to identify potential biomarkers for diagnosing TED in tear fluid. We obtained two expression profiling datasets related to TED lacrimal gland samples from the Gene Expression Omnibus (GEO). Subsequently, we combined the two separate datasets and conducted differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) on the obtained integrated dataset. The genes were employed for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The genes were intersected with the secretory proteins profile to get the potential proteins in the tear fluid. Machine learning techniques were then employed to identify optimal biomarkers and develop a diagnostic nomogram for predicting TED. Finally, gene set enrichment analysis (GSEA) and immune infiltration analysis were conducted on screened hub genes to further elucidate their potential mechanisms in TED. In our analysis of the integrated TED dataset, we identified 2,918 key module genes and 157 differentially expressed genes and finally obtained 84 lacrimal-associated key genes. Enrichment analysis disclosed that these 84 genes primarily pertain to endoplasmic reticulum organization. After intersecting with the secretory proteins, 13 lacrimal gland-associated secretory protein genes (LaSGs) were identified. The results from machine learning indicated the substantial diagnostic value of dyslexia associated gene (KIAA0319) and peroxiredoxin4 (PRDX4) in TED-associated lacrimal gland lesions. The two hub genes were chosen as candidate biomarkers in tear fluid and employed to establish a diagnostic nomogram. Furthermore, single-gene GSEA results and immune cell infiltration analysis unveiled immune dysregulation in the lacrimal gland of TED, with KIAA0319 and PRDX4 showing significant associations with infiltrating immune cells. We uncovered the distinct pathophysiology of TED-associated lacrimal gland enlargement compared to TED-associated orbital adipose tissue enlargement. We have demonstrated the endoplasmic reticulum-related pathways involved in TED-associated lacrimal gland lesions and established a diagnostic nomogram for TED utilizing KIAA0319 and PRDX4 through integrated bioinformatics analysis. This contribution offers novel insights for non-invasive, prospective diagnostic approaches in the context of TED.

Removable dental prostheses for patients with Sjögren's syndrome

Sjögren's syndrome (SS) is a chronic autoimmune condition primarily affecting the salivary and lacrimal glands, leading to pronounced dry mouth (xerostomia) and dry eyes. These symptoms create unique challenges for SS patients requiring removable dental prostheses, as the lack of saliva significantly impacts the retention, comfort, and overall effectiveness of these devices. Without adequate saliva, prosthetic retention diminishes, and patients frequently experience issues such as mucosal irritation and increased susceptibility to infections. To address these issues, tailored material choices are critical in designing effective prosthetic solutions. Soft liners, moisture-retentive acrylics, and antimicrobial coatings are among the innovations improving both retention and comfort for SS patients. The aesthetic and functional outcomes of prosthetic solutions are also essential considerations. Enhanced retention mechanisms, such as implant-supported overdentures, not only improve masticatory performance but also aid in preserving the patient’s facial profile and lip support. Advanced materials offering translucency and color stability contribute to a more natural appearance, which is critical for patient satisfaction. The maintenance of these prostheses requires specific care routines to mitigate microbial buildup and tissue irritation. Specialized cleaning agents and salivary substitutes help maintain hygiene and reduce discomfort, while regular follow-up visits enable timely adjustments to accommodate tissue changes and extend the prosthesis lifespan. Implementing a comprehensive approach that considers material selection, functional and aesthetic outcomes, and maintenance strategies can greatly enhance the quality of life for SS patients. By understanding and addressing the specific needs associated with xerostomic conditions, dental professionals can provide prosthetic solutions that offer both reliability and comfort in this challenging context. Regular patient education and diligent care routines remain essential to ensure the long-term success and durability of removable dental prostheses for individuals with SS.

IgG4-related Breast Disease: Review of the Literature.

IgG4-related disease (IgG4-RD) is a rare illness with inflammatory and fibrotic changes in affected organs such as pancreas, thyroid, salivary or lacrimal glands, and retroperitoneal space; rarely other organs may be involved. IgG4-related breast disease (IgG4-BD) is very rare and generally presents as a lump or mastitis. IgG4-BD as a presenting feature of IgG4-RD is extremely rare. Hence, this paper reviews the known (n=48) IgG-BD cases reported in the literature to date. The majority of cases were diagnosed on routine mammography or during assessment for other clinically significant features. The absence of a lump border, and especially the absence of calcifications on ultrasonography, mammography, or computed tomography, is typical for IgG4-BD. Characteristic IgG4-BD pathological findings were dense lymphoplasmacytic infiltration with stromal fibrosis, and more than 10% IgG4+ plasma cells/high-power field (HPF); the mean percentage of IgG4+/IgG+ plasma cells was 54.2%, and only one-third of the patients had all "classical" signs of IgG4-BD including storiform fibrosis and obliterative phlebitis. Most of the cases had a benign course and responded to surgical excision with or without steroid therapy.

Molecular Mechanisms Responsible for Mesenchymal Stem Cell-Dependent Attenuation of Tear Hyperosmolarity and Immune Cell-Driven Inflammation in the Eyes of Patients with Dry Eye Disease

Background: Dry eye disease (DED) is a chronic condition characterized by a decrease in tear production or an increase in tear evaporation, leading to inflammation and damage of the ocular surface. Dysfunction of ion channels, tear hyperosmolarity and immune cell-driven inflammation create a vicious circle responsible for the pathological changes in the eyes of DED patients. Mesenchymal stem cells (MSCs) are adult, rapidly proliferating stem cells that produce a large number of immunoregulatory, angiomodulatory, and growth factors that efficiently reduce tear hyperosmolarity-induced pathological changes, inhibit harmful immune response, and provide trophic support to the injured corneal and conjuctival epithelial cells, goblet cells and acinar cells in lacrimal glands of DED patients. Methods: An extensive research in the literature was implemented in order to elucidate the role of MSCs in the attenuation of tear hyperosmolarity and eye inflammation in patients suffering from DED. Results: Findings obtained in preclinical and pilot clinical studies demonstrated that MSCs reduced tear hyperomsolaity-induced pathological changes and suppressed immune cell-driven eye inflammation. Additionally, MSC-based therapy managed to successfully address the most severe DED-related conditions and complications. Conclusions: MSCs should be considered as potentially new therapeutic agents for the treatment of severe DED.

Granulomatosis with polyangiitis with lacrimal gland enlargement and pancreatic swelling: case report and literature review.

A 62-year-old man had bilateral eyelid swelling for 4 months. Two months before admission, he developed fatigue and lost 5 kg of bodyweight. Further examination revealed elevated serum C-reactive protein, normal angiotensin-converting enzyme, elevated proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA), and normal IgG4 concentration. Chest X-ray and computed tomography showed no enlarged hilar lymph nodes, but positron emission tomography-computed tomography showed fluorodeoxyglucose accumulation in both lacrimal glands, in lung nodules, and in the pancreas. Tissue biopsies of the lacrimal glands and pulmonary nodules showed granuloma with giant cells, but no IgG4-positive cells or fibrosis. Pancreatic tissue showed no findings of autoimmune pancreatitis. In the 2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis, the total score was 10 points. Final comprehensive diagnosis was granulomatosis with polyangiitis, based on the negative results of differential diseases, such as IgG4-related diseases and sarcoidosis. Prednisolone 60 mg/day was started on day 8, and rituximab 500 mg/body/week on day 12. After beginning treatment, general malaise and lacrimal gland enlargement were resolved, PR3-ANCA and C-reactive protein became negative, and the nodular shadow in the lungs disappeared. This is the first report of granulomatosis with polyangiitis presenting both lacrimal gland and pancreatic lesions.

Non-invasive miRNAs for early detection and diagnosis of lacrimal adenoid cystic carcinoma.

Lacrimal adenoid cystic carcinoma (LACC) is one of the most common malignant epithelial tumors of the lacrimal gland, characterized by high rates of local recurrence, distant metastases, and tumor-related mortality. This malignancy impairs the lacrimal gland's ability to secret tears, thereby disrupting the normal function of the ocular surface. Due to ineffective diagnostic approaches and the complex anatomical location of the lacrimal gland within the orbit, many LACC patients are often diagnosed at the later stages. Therefore, it is urgent to develop a simple and convenient method for early detection of LACC through biomarker analysis by liquid biopsies, such as blood or tears. Various microRNAs (miRNAs) derived from liquid biopsies have been shown to serve as biomarkers for early diagnosis of tumors. In the present study, we screened LACC-specific miRNAs using miRNA microarray analysis in both primary and recurrent patient groups. We then validate their expression by qPCR experiments conducted in tissues, cell lines, tear fluid and serum to explore the association between these miRNAs and LACC development and prognosis. Our findings reveal that hsa-miR-200b-3p, hsa-miR-200c-3p and hsa-miR-141-3p are significantly upregulated in LACC, and the microarray data showed that these three miRNAs were significantly elevated in the recurrence group compared to the primary group. In conclusion, detecting miRNA expression in tear fluid and serum provides non-invasive biomarkers for the early diagnosis of LACC and may facilitate monitoring outcomes related to lacrimal gland diseases.

Optimizing surgical approaches for lacrimal gland adenoid cystic carcinoma to minimize cross-organ invasion.

To evaluate the outcomes of eye-sparing surgery for lacrimal gland adenoid cystic carcinoma and the impact on tumor recurrence and orbital integrity. The study enrolled four patients with recurrent lacrimal gland adenoid cystic carcinoma. The outcome focused on the relevance of the integrity of the lateral orbital wall to the occurrence of extraorbital metastasis in the local recurrence of lacrimal gland adenoid cystic carcinoma. Three patients underwent eye-sparing surgery via lateral orbitotomy without postoperative radiotherapy, and one patient who underwent eye-sparing surgery via sub-brow approach. These four patients all demonstrated a recurrence involving the invasion of extraorbital tissues as metastatic form through surgical bone seams. Preserving intact orbital bone tissue is crucial for mitigating direct cross-organ metastasis of lacrimal gland adenoid cystic carcinoma. The findings suggest avoiding the lateral orbitotomy approach with no or limited orbital bone wall invasion.

Psychological resilience in patients with primary Sjögren's syndrome: effect of involvement of major salivary and lacrimal glands.

The aim of this study was to assess whether the involvement of major salivary and lacrimal glands in primary Sjögren's syndrome (pSS) affected the psychological resilience of patients. This cross-sectional study included 116 patients with pSS. Data were collected through clinical examinations, measurement of salivary flow rates (SFRs), and from Schirmer's test, as well as from patient-reported outcome measures (PROMs), such as the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index (ESSPRI), Brief Resilience Scale (BRS), Work Productivity and Activity Impairment (WPAI), Oral Health Impact Profile-14 (OHIP-14), and the Hospital Anxiety and Depression Scale (HADS). Hyposalivation was defined as an unstimulated SFR of≤0.1mL/min. The BRS score (mean±SD=2.60±0.69) was lower in patients with recurrent parotitis (2.11±0.37) than in those without recurrent parotitis (2.67±0.86), in the whole group. In patients with an unacceptable symptom state (ESSPRI score≥5 points), a lower BRS score was observed in patients with both hyposalivation and ocular dryness (2.59±0.69) than in patients with isolated hyposalivation (2.84±0.84). The BRS score was also negatively associated with the WPAI-Daily Impairment and OHIP-14 scores in patients with hyposalivation as well as with HADS-A (the seven items of HADS relating to the anxiety dimension) and HADS-D (the seven items of HADS relating to the depression dimension) in the whole group. The results suggest that psychological resilience in pSS may be affected by recurrent parotitis, the levels of anxiety and depression, as well as hyposalivation with ocular dryness.

Axis "microbiota – gut – eye": a review

Every organ in the human body has its own microbiota, and the eye, a complex multi-component organ, is no exception. Due to the limitations of traditional methods, detailed study of the ocular microbiome began only in 2010 as part of the Eye Microbiome Project, when advances in research methods made it possible to obtain detailed data, although there had been debate previously about whether microorganisms were even able to attach to the ocular surface due to the layers of the tear film, which have antibacterial properties. The cornea, conjunctiva, lacrimal glands and tear film, meibomian glands and microbiome form the microenvironment of the ocular surface, interacting together and resisting irritants, allergens and pathogens. Homeostasis of the ocular microbiota is critical for maintaining the health of the visual organ. Most microorganisms are found on the cornea and conjunctiva, and modern research methods, including 16S rRNA sequencing, have allowed us to establish the "core" of the ocular surface microbiota, identifying the most common types: Staphylococcus, Corynebacterium, Propionibacterium, and Streptococcus, although the exact composition of the “core” remains debatable. Many factors can influence the composition of the microbiome, including age, contact lens wear, ophthalmic medications, and antibiotics. Like the microbiome of many other organs, the ocular surface microbiome is influenced by the gut microbiome: this relationship has been called the "microbiota – gut – eye" axis. Within the "gut – eye" axis, healthy gut microbiota produce short-chain fatty acids, indoles, polyamines, and other substances that have a beneficial effect on the immune system and retinal health. The state of dysbiosis leads to disruption of homeostasis, and the increasing inflammatory reaction can contribute to damage to the optic nerve and progression of eye disease. Some ophthalmologic diseases, such as diabetic retinopathy, age-related macular degradation, choroidal neovascularization, uveitis, primary open-angle glaucoma, Sjogren's syndrome, dry eye syndrome are associated with dysbiosis of the intestinal microbial composition. Correction of intestinal dysbiosis using various methods can lead to a decrease in the risk of eye diseases, although additional research is needed to discover new methods for treating ophthalmologic pathologies along the "microbiota – gut – eye" axis.

Immune and non-immune mediators in the fibrosis pathogenesis of salivary gland in Sjögren's syndrome.

Sjögren's syndrome (SS) or Sjögren's disease (SjD) is a systemic autoimmune disease clinically manifested as sicca symptoms. This disease primarily impacts the functionality of exocrine glands, specifically the lacrimal and salivary glands (SG). SG fibrosis, an irreversible morphological change, is a severe consequence that occurs in the later stages of the disease due to sustained inflammation. However, the mechanism underlying SG fibrosis in SS remains under-investigated. Glandular fibrosis may arise from chronic sialadenitis, in which the interactions between infiltrating lymphocytes and epithelial cells potentially contributes to fibrotic pathogenesis. Thus, both immune and non-immune cells are closely involved in this process, while their interplays are not fully understood. The molecular mechanism of tissue fibrosis is partly associated with an imbalance of immune responses, in which the transforming growth factor-beta (TGF-β)-dependent epithelial-mesenchymal transition (EMT) and extracellular matrix remodeling are recently investigated. In addition, viral infection has been implicated in the pathogenesis of SS. Viral-specific innate immune response could exacerbate the autoimmune progression, resulting in overt inflammation in SG. Notably, post-COVID patients exhibit typical SS symptoms and severe inflammatory sialadenitis, which are positively correlated with SG damage. In this review, we discuss the immune and non-immune risk factors in SG fibrosis and summarize the evidence to understand the mechanisms upon autoimmune progression in SS.

Single-Cell Transcriptomics Reveals a Pivotal Role of DOCK2 in Sjögren Disease.

Sjögren disease (SjD) is an autoimmune condition characterized by the dysfunction of the salivary and lacrimal glands. The study aimed to decipher the pathogenic cell populations and their immunologic pathways in the salivary glands. We further determined the therapeutic effect of inhibiting dedicator of cytokinesis 2 (DOCK2) shared by novel clusters of CD8+ T cells in an SjD mouse model. This study employed single-cell RNA sequencing to examine the composition and dynamics of immune cells in the salivary glands of SjD mice. By analyzing the transcriptomic data and employing clustering analysis, a specific target was identified, leading to the treatment of mice with a targeted inhibitor. The results showed diverse immune cell types, including B cells, CD4+ T cells, CD8+ T cells, macrophages, and natural killer cells. We identified specific clusters possessing phenotypic characteristics of immune cell subpopulations, thereby showing specific genes/pathways associated with the disease. The most striking finding was the elevated expression of DOCK2 in CD8+ T cells in the SjD model. This discovery is significant because subsequent treatment with a DOCK2 inhibitor 4-[3-(2-Chlorophenyl)-2-propen-1-ylidene]-1-phenyl-3,5-pyrazolidinedione (CPYPP) led to a marked amelioration of SjD signs. The effectiveness of DOCK2 inhibition in alleviating SjD signs highlights the potential of DOCK2 as a therapeutic target, opening new avenues for treatment strategies that could modulate the immune response more effectively in SjD.