Search Results (254)

Dry eye disease (DED) is a complex ocular surface disorder characterized by tear film instability, chronic inflammation, and epithelial damage, for which current treatments remain limited. Marine-derived bioactive oligosaccharides have attracted increasing interest due to their diverse pharmacological activities and favorable safety profiles. In this study, we investigated the therapeutic potential of neoagarotetraose (NA4), a marine oligosaccharide derived from red algal agar, in a murine model of DED. DED was induced in eight-week-old female C57BL/6 mice by topical instillation of 0.2% benzalkonium chloride for seven consecutive days. NA4 was administered topically at concentrations of 125, 250, and 500 mg/L. Therapeutic outcomes were evaluated by tear secretion, corneal fluorescein staining, histopathological analysis, immunofluorescence staining for Ki67, F4/80, IL-1β, IL-6, and TNF-α, TUNEL assay for apoptosis, and ELISA for cytokine levels. NA4 treatment significantly improved tear secretion and reduced corneal fluorescein staining scores. Histological analysis revealed that NA4 preserved corneal epithelial thickness and restored conjunctival goblet cell density. Immunofluorescence analysis revealed that NA4 reversed inflammation-associated epithelial hyperproliferation and attenuated macrophage infiltration. Moreover, NA4 markedly suppressed the expression and tissue levels of IL-1β, IL-6, and TNF-α, and attenuated corneal epithelial apoptosis, with the 500 mg/L NA4 group showing no significant difference in efficacy compared to the positive control 0.1% sodium hyaluronate. These findings demonstrate that NA4, a marine-derived oligosaccharide, exerts multi-targeted protective effects against DED by improving tear film stability, preserving ocular surface integrity, suppressing inflammation, and reducing apoptosis. Our study highlights the potential of marine oligosaccharides such as NA4 as promising candidates for ocular surface disease management and supports the further exploration of marine resources for ophthalmic therapeutic applications. Full article

Background: Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability, inflammation, and neurosensory abnormalities. Current therapies remain limited by slow onset and suboptimal efficacy. Teriflunomide, an immunomodulatory agent approved for multiple sclerosis, has shown therapeutic potential in DED, but its multi-target mechanisms remain unclear. Methods: We employed an integrated computational and transcriptomic framework combining ADMET profiling, multi-dataset transcriptomic integration, and single-cell RNA sequencing (scRNA-seq) to identify disease-relevant targets. Candidate genes were further refined through molecular docking and 50 ns molecular dynamics (MD) simulations. The AetherCell virtual cell model was applied to evaluate both the concordance between target perturbation and drug-induced responses and the potential mechanistic roles of candidate targets. Results: Transcriptomic integration identified 16 consensus genes across heterogeneous DED models, which were further localized to disease-relevant epithelial and immune cell populations by scRNA-seq. Molecular simulations prioritized three core targets—CTSS, STAT1, and PTGS1—based on binding stability and affinity. AetherCell simulations demonstrated that perturbation of these targets not only recapitulated teriflunomide-induced transcriptional and pathway changes but also revealed their distinct mechanistic contributions, including epithelial barrier regulation (CTSS), microvascular and lipid homeostasis (PTGS1), and inflammation suppression coupled with tissue repair (STAT1). Conclusions: Teriflunomide exerts therapeutic effects in DED through coordinated multi-target regulation involving inflammation control, barrier restoration, and tissue repair. This study provides a rationale for novel therapeutic targets in dry eye disease, establishes a paradigm for applying virtual cell modeling to elucidate drug mechanisms, and offers a bioinformatics framework for validating drug repositioning outcomes. Full article

The gut microbiome regulates host metabolism, barrier integrity, and immune homeostasis through microbe–host signaling and bioactive metabolites. Growing evidence suggests that dysbiosis may also influence ocular immune privilege and blood–retinal barrier stability, supporting the emerging concept of the gut–eye axis. This narrative review aimed to integrate retinal, uveal, and ocular surface disorders within a shared functional framework, with emphasis on recurring mechanistic pathways and their translational relevance rather than on single diseases or isolated taxonomic findings. The review was based on a literature search of PubMed and Scopus and primarily included English-language studies published between 2015 and 2025, with earlier seminal papers included when needed. The search was last updated in March 2026, and 101 sources were included in the final narrative synthesis. Across age-related macular degeneration, diabetic retinopathy, glaucoma, uveitis, dry eye disease, and Sjögren’s syndrome, the most consistent microbiome-related signals were functional rather than taxonomic. Recurrent mechanistic themes included Th17/Treg immune programming, barrier dysfunction with microbial product translocation, and systemic metabolite signaling, particularly involving short-chain fatty acids, bile acid receptor pathways, and tryptophan-derived metabolites. Age-related macular degeneration and diabetic retinopathy showed the strongest multi-layered support, whereas uveitis provided a compelling immune-centered biological model that remains limited by treatment-related confounding in human studies. In glaucoma and ocular surface disease, evidence supports biological plausibility, especially in relation to neuroinflammation, mucosal immune dysregulation, and metabolite-dependent anti-inflammatory pathways, although much of the available human literature remains associative. Overall, current evidence supports dysbiosis as a disease modifier that may influence ocular inflammation, angiogenesis, neurodegeneration, and barrier stability. However, clinical translation remains limited by cohort heterogeneity, methodological variability, and incomplete control of confounding factors. Further progress will depend on longitudinal multi-omics cohorts and controlled intervention trials focused on actionable microbial functions. Full article

Dry eye disease (DED) is a common ocular surface disorder characterized by instability of the tear film, inflammatory responses, and epithelial damage, and therapeutic interventions directed at these fundamental pathogenetic processes are still insufficient. This research aimed to evaluate the medicinal efficacy of glycyrrhizic acid (GA) and to unravel the underlying molecular pathways through which it exerts its protective role in DED. A benzalkonium chloride-induced mouse model and a hyperosmolarity-induced human corneal epithelial cell model were established. Corneal epithelial injury, tear secretion, and goblet cell density were evaluated in vivo, while cellular responses and related signaling pathways were examined using RT-qPCR, Western blotting, flow cytometry, and immunofluorescence. GA treatment alleviated corneal epithelial damage, increased tear secretion, and improved goblet cell density in mice. In vitro, GA reduced inflammatory responses, as evidenced by decreased tumor necrosis factor-α (TNF-α) expression, and helped preserve epithelial barrier integrity, accompanied by reduced matrix metalloprotease 9 (MMP9) levels. Further analysis suggested that GA suppressed pyroptosis through regulation of the high mobility group box 1 (HMGB1)/lysosomal membrane permeabilization (LMP)/cathepsin B (CTSB) pathway and attenuated oxidative stress via activation of the nuclear factor erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD (P)H:quinone oxidoreductase 1 (NQO1) axis. In addition, GA improved mitochondrial function, as indicated by decreased reactive oxygen species levels, restored membrane potential, and enhanced adenosine triphosphate (ATP) production. Taken together, these findings indicate that GA may alleviate hyperosmolarity-induced DED by modulating inflammation, oxidative stress, mitochondrial dysfunction, and epithelial barrier damage, underscoring its viability as a remedial candidate. Full article

Rheumatoid arthritis (RA) is a systemic autoimmune disease that can involve the ocular surface and deeper ocular tissues, leading to a spectrum of ophthalmic manifestations ranging from dry eye disease to vision-threatening inflammation, such as scleritis and peripheral ulcerative keratitis (PUK). This paper presents the results of a narrative review conducted using PubMed and Google Scholar from database inception to March 2026. Eligible publications describing clinical features and management of RA-associated ocular disease were synthesized, and no unpublished data were included. According to the literature, dry eye disease (DED) is the most frequent ocular manifestation of RA, and it is primarily managed with lubrication and topical anti-inflammatory therapies, including cyclosporine and lifitegrast. Additional options for refractory disease include neurostimulation and evaporation-targeted therapy. Scleritis and PUK are less common but represent severe inflammatory complications that generally require systemic immunosuppression. Conventional management includes systemic corticosteroids and steroid-sparing agents such as methotrexate (MTX), azathioprine (AZA), cyclophosphamide (CYC), and mycophenolate mofetil (MMF) in aggressive cases. Escalation to biologic disease-modifying antirheumatic drugs (bDMARDs), specifically tumor necrosis factor-alpha (TNF-α) inhibitors and rituximab (RTX), is supported for refractory scleritis and corneal melt, although evidence is largely observational. Among anti-TNF agents, monoclonal antibodies, such as infliximab and adalimumab, appear more effective than etanercept for ocular inflammation. Rituximab is preferred for vasculitis-associated or refractory disease, and Janus Kinase (JAK) inhibitors represent an emerging option requiring careful safety monitoring. Evidence for DED therapies includes randomized controlled trials (RCTs), whereas data for RA-associated scleritis and PUK are largely derived from registries, case series, and case reports. Prospective studies with standardized ocular outcomes are needed to refine treatment algorithms and compare the effectiveness of biologic versus targeted synthetic agents. Full article

Background/Objectives: As scleral lens (SL) use continues to expand, particularly for medically necessary management of corneal irregularity and ocular surface disease, it is important to determine if wear of these lenses is associated with eyelid disease. This study evaluated habitual SL wearers for meibomian gland obstruction, meibum quality, and signs of lid margin inflammation. Methods: Eligible participants wore scleral lenses in one or both eyes for any indication and had been wearing their current lens design(s) for at least six months, with habitual wear of ≥5 h per day, six days per week. Eyelid inflammation metrics were specifically assessed. Results: Forty-nine scleral lens wearers (32 females) were enrolled. Upper lid wiper epitheliopathy (LWE) was present in 21 eyes (43%), and lower LWE was present in 15 eyes (31%). Thirty-nine eyes (80%) had expressible meibomian glands. Eyes with no expressible meibum were significantly higher in ocular surface disease (39%, 7/18) than corneal irregularity (11%, 3/27) (p = 0.03). Lid margin telangiectasia was present in wearers with ocular surface disease (61%, 11/18) and corneal irregularity (19%, 5/26) (p = 0.005). Conclusions: Eyelid disease was common among habitual scleral wearers regardless of indication for lens use. Eyes with ocular surface disease demonstrated a higher prevalence of meibomian gland obstruction and lid margin telangiectasia compared to those with corneal irregularity. Full article

Corneal alkali burn induces severe inflammation and tissue damage, leading to loss of corneal transparency and vision impairment. In this study, we evaluated the therapeutic potential of rapamycin (RAPA) compared with cyclosporine A (CsA) in a mouse model of corneal alkali burn, focusing on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)–mediated inflammatory signaling and its impact on corneal wound healing and repair. Notably, RAPA robustly suppressed NF-κB activation, reduced infiltration of F4/80 macrophages and MPO neutrophils, and downregulated pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. RAPA also markedly inhibited corneal neovascularization, as evidenced by decreased VEGF expression, reduced CD31 vessel formation, and suppression of Ang-2. RAPA substantially inhibited pathological fibrotic remodeling by reducing TGF-β1 expression, attenuating myofibroblast activation (α-SMA), decreasing collagen III deposition, and modulating matrix remodeling through suppression of MMP-9. Crucially, RAPA preserved epithelial barrier integrity by maintaining occludin expression, supported proper epithelial differentiation through sustained expression of CK12, and enhanced mucin layer stability by increasing MUC1 expression. It also restored tear production, reduced apoptotic cell death (TUNEL), and decreased dysregulated epithelial proliferation (Ki67). In conclusion, RAPA showed superior efficacy compared with CsA, primarily by enhancing corneal wound healing and facilitating structural and functional outcomes in the burned cornea. These findings underscore RAPA as a promising therapeutic candidate for ocular surface repair and vision restoration in extensive corneal injury. Full article

Corneal neovascularization (CNV) in dogs causes chronic ocular surface inflammation, which may disrupt tear film stability and meibomian gland function. As bevacizumab inhibits abnormal vessel growth and affects tear composition, it may benefit dogs with ocular surface disorders. The aim of this pilot study was to evaluate the effects of bevacizumab eye drops on the ocular surface in dogs with chronic CNV. Fourteen eyes from nine client-owned dogs were included. Dogs received either preserved (B_BAC-group) or unpreserved (B-group) 0.25% bevacizumab eye drops twice daily for 28 days. Re-examinations occurred one week after treatment initiation, at the end of treatment, and three months later. An ocular surface analyzer was used to assess tear composition and meibomian glands via interferometry, tear meniscus height, and meibography. Ocular and systemic toxicities were monitored, and clinical signs were scored. Serum VEGF levels were measured via ELISA before and after treatment. No statistically significant changes in intraocular pressure, tear production, or systemic VEGF levels were observed. Statistically significant improvements were noted in conjunctival hyperemia and chemosis in both groups, ocular discharge in the B_BAC-group, and fluorescein uptake in the B-group. Both formulations were safe and well tolerated. These preliminary findings suggest that topical bevacizumab may have potential benefits for CNV and ocular surface disorders in dogs, although larger studies are needed. Full article

Background/Objectives: To evaluate the relationships between meibomian gland dysfunction (MGD), ocular surface parameters, and matrix metalloproteinase-9 (MMP-9)-mediated inflammation in glaucoma patients, we specifically assessed the impact of prostaglandin analogue use, preservative exposure, and number of medications. Methods: This retrospective cross-sectional study included patients treated with topical antiglaucoma medications for at least six months. Meibomian gland expressibility, meibum quality, and MGD grade were assessed along with tear film break-up time (TBUT), Schirmer I test, and Oxford staining score. Tear MMP-9 levels were measured using a Point-of-Care immunoassay (InflammaDry^®) and graded on a 0 to 4 scale. Results: Elevated MMP-9 grades were significantly correlated with worsening meibum expressibility, meibum quality, and MGD grade (all p < 0.001), whereas no significant associations were found with traditional parameters such as TBUT and Schirmer I test. Prostaglandin analogue use was associated with worse meibomian gland parameters and higher MMP-9 levels compared to non-use. Patients receiving preservative-containing medications exhibited poorer meibomian gland parameters and MMP-9 levels, as well as worse corneal staining scores. An increased number of medications was associated with a stepwise deterioration in meibomian gland function and elevated MMP-9 levels. Conclusions: Prostaglandin analogue use, preservative exposure, and increased number of medications are significant factors associated with the exacerbation of MGD and ocular surface inflammation. Semi-quantitative grading of tear MMP-9 revealed a stepwise association with meibomian gland dysfunction severity that was not detected by conventional dry eye metrics, indicating that MMP-9 may be considered a potential indicator of subclinical ocular surface inflammation in glaucoma patients. Full article

Corneal alkali burns represent one of the most severe forms of ocular surface injury and frequently result in persistent inflammation, corneal neovascularization, stromal remodeling, and permanent visual impairment. Current therapeutic approaches incompletely control the inflammatory mechanisms that sustain pathological angiogenesis and tissue disorganization. In this study, we evaluated the effects of a transglutaminase-binding fusion protein (FP) in a rat model of alkali-induced corneal injury. Following standardized alkali burns, animals were treated topically with FP, secretory leukocyte protease inhibitor (SLPI), or Buffer. Corneal epithelial healing, opacity, and neovascularization were assessed clinically and by digital image-based quantification, while histological and immunofluorescence analyses were used to evaluate stromal organization and vascular invasion. Molecular mechanisms were investigated by RT-qPCR and Western blot analysis of key inflammatory, angiogenic, and signaling mediators. FP treatment significantly accelerated corneal re-epithelialization, reduced corneal opacity, and markedly attenuated corneal neovascularization compared to SLPI and Buffer controls. These effects were associated with coordinated downregulation of pro-inflammatory cytokines and angiogenic mediators, including TNF-α, IL-17, VEGF, and cPLA₂. Notably, FP suppressed transglutaminase 2 expression and induced early and sustained downregulation of NF-κB pathway components, identifying modulation of an upstream inflammatory pathway central to corneal angiogenesis and stromal remodeling. Collectively, these findings demonstrate that FP effectively limits inflammation-driven corneal neovascularization and tissue remodeling following alkali injury, supporting its potential as a disease-modifying therapeutic strategy for inflammatory ocular surface disorders. Full article

At present, the clinical management of ocular inflammatory diseases predominantly relies on chemically synthesized therapeutic agents. Although these therapies demonstrate established efficacy, their long-term use is associated with substantial economic burden. In addition, they may cause ocular side effects and systemic adverse reactions involving the cardiovascular, hepatic, and renal systems. In contrast, natural products have attracted increasing attention in recent years because many are accessible, relatively cost-effective, and potentially well tolerated. Studies indicate that various natural products exert anti-inflammatory and immunomodulatory effects by inhibiting inflammatory signaling pathways such as NF-κB and MAPK, regulating immune cell function and alleviating oxidative stress responses. These multifunctional properties support their potential therapeutic value in various inflammatory diseases. Notably, several natural products have shown potential benefits in clinical trials; however, their investigation and application in ocular diseases remain relatively limited. In this review, we focus on uveitis and dry eye disease (DED) as representative ocular disease models and systematically summarize the current research progress on four natural products—Paeonia lactiflora extracts, resveratrol and its derivatives, curcumin, and boswellic acids in experimental studies of ocular diseases. We particularly focus on their effects in alleviating ocular surface inflammation and intraocular inflammatory responses through their immunomodulatory mechanisms. This review aims to provide a mechanistic framework for understanding the potential role of natural products as complementary or alternative strategies to current therapeutic approaches, while informing the development of novel therapeutics and future research directions in ocular diseases. Full article

Thyroid eye disease (TED) is an autoimmune inflammatory disorder primarily affecting orbital tissues, but ocular surface and adnexal involvement represent a frequent and clinically significant component of disease burden. Beyond mechanical exposure resulting from eyelid retraction and proptosis, TED-associated ocular surface disease arises from complex interactions between immune activation, epithelial stress, glandular dysfunction, and altered neuro-epithelial signaling. Increasing use of systemic immunomodulatory therapies, biologics, and orbital radiotherapy has improved control of orbital inflammation; however, their molecular and cellular effects on ocular surface homeostasis remain incompletely defined. This review summarizes current evidence on the cellular and molecular mechanisms underlying ocular surface dysfunction in TED and examines how disease-modifying therapies influence epithelial integrity, tear film stability, meibomian and lacrimal gland function, and local immune signaling. Key pathways discussed include cytokine-mediated inflammation, thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor crosstalk, pro-fibrotic signaling, neuro-inflammatory mechanisms, and epithelial stress responses involving mitogen-activated protein kinase and nuclear factor kappa B pathways. We further highlight the challenge of disentangling therapy-induced molecular effects from persistent exposure-related mechanical stress. Understanding how TED therapies modulate ocular surface and adnexal homeostasis is essential for optimizing integrated management strategies that address both orbital inflammation and long-term ocular surface stability. Full article

The ocular surface system, essential for maintaining visual function, is highly susceptible to a range of ocular surface diseases (OSDs) that significantly impair patients’ quality of life. Current treatments for OSDs often face limitations including low bioavailability, A lack of targeted delivery, and an inadequate capacity to fully address the complex pathophysiology involving inflammation, oxidative stress, and impaired tissue repair. In recent years, exosomes have emerged as promising cell-free therapeutic platforms for OSDs. This review evaluates their therapeutic potential across the OSD spectrum, focusing on three key aspects: mechanisms—modulation of inflammation, oxidative stress, and tissue repair via bioactive cargo; applications—preclinical therapeutic effects in dry eye disease, corneal injury, keratitis, and transplant rejection; and optimization strategies—engineering approaches and biomaterial integration to enhance stability, targeting, and ocular retention. We also discuss critical challenges in standardization, scalable production, and clinical translation, highlighting future directions for exosome-based OSD therapies. Full article

Dry eye disease (DED) is a complex, multifactorial, progressive disease that has consequences both for individuals and society. Symptoms reported by patients include discomfort in the eye and periodic blurred vision, while in the broader perspective, the disease is associated with economic burdens and challenges for healthcare systems. Globally, dry eye disease remains a growing problem observed in many countries. It is estimated that symptoms of dry eye syndrome occur in approximately 10 to 20 per cent of people over the age of 40. This prevalence is on the rise, which is associated with both the aging population and increased incidence among younger adults. In this group, factors such as contact lens wear and prolonged use of digital devices are considered to be contributing factors. Further epidemiological studies, conducted in different regions of the world, covering diverse populations and a wide range of age groups, with a particular focus on younger cohorts, may contribute to a more accurate understanding of the prevalence of dry eye disease. There are more and more methods of diagnosing DED. In addition to well-known procedures like the Schirmer test or tear break-up time, there are also methods that focus on the evaluation of the tear film or imaging of the ocular surface. Moreover, usage of artificial intelligence is also playing a significant role in it. However, the key issue in individual cases is introducing the most effective treatment based on combining available substances, including corticosteroids, antibiotics and supplements, which leads to a reduction in inflammation and improvement in visual comfort. Full article

Dry eye disease (DED) is an ocular surface disorder characterized by tear film instability, inflammation, epithelial damage, and neurosensory abnormalities. Due to its multifactorial etiology and pathophysiology, conventional therapies that focus on lubrication and immunosuppression often fall short in addressing the neuropathic component of ocular pain experienced by a growing subset of patients. Recent developments in sensory neuroscience have highlighted the pivotal role of ion channels in mediating ocular surface homeostasis, pain signaling, and inflammation. This review examines the role of the following major ion channel families in the pathophysiology of DED and neuropathic ocular pain: transient receptor potential (TRP) channels, voltage-gated sodium (Nav) channels, and purinergic P2X receptors. The review details their anatomical distribution, molecular function, and responses to environmental stimuli such as heat, cold, osmolarity, and injury. Current treatments, such as artificial tears, anti-inflammatory drops, and systemic neuromodulators, are also reviewed in relation to their effects on ion channel modulation. Additionally, emerging therapies that directly target sensory transduction pathways are introduced. This review highlights the therapeutic potential of ion channel modulation in personalizing treatment for patients with ocular surface pain, particularly those with neuropathic features unresponsive to standard care. Full article