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1.
Medicina (Kaunas) ; 60(5)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38792893

ABSTRACT

Background and Objectives: The risks of uveitis development among pediatric patients with Down syndrome (DS) remain unclear. Therefore, we aimed to determine the risk of uveitis following a diagnosis of DS. Materials and Methods: This multi-institutional retrospective cohort study utilized the TriNetX database to identify individuals aged 18 years and younger with and without a diagnosis of DS between 1 January 2000 and 31 December 2023. The non-DS cohort consisted of randomly selected control patients matched by selected variables. This included gender, age, ethnicity, and certain comorbidities. The main outcome is the incidence of new-onset uveitis. Statistical analysis of the uveitis risk was reported using hazard ratios (HRs) and 95% confidence intervals (CIs). Separate analyses of the uveitis risk among DS patients based on age groups and gender were also performed. Results: A total of 53,993 individuals with DS (46.83% female, 58.26% white, mean age at index 5.21 ± 5.76 years) and 53,993 non-DS individuals (45.56% female, 58.28% white, mean age at index 5.21 ± 5.76 years) were recruited from the TriNetX database. Our analysis also showed no overall increased risk of uveitis among DS patients (HR: 1.33 [CI: 0.89-1.99]) compared to the non-DS cohort across the 23-year study period. Subgroup analyses based on different age groups showed that those aged 0-1 year (HR: 1.36 [CI: 0.68-2.72]), 0-5 years (HR: 1.34 [CI: 0.75-2.39]), and 6-18 years (HR: 1.15 [CI: 0.67-1.96]) were found to have no association with uveitis risk compared to their respective non-DS comparators. There was also no increased risk of uveitis among females (HR: 1.49 [CI: 0.87-2.56]) or males (HR: 0.82 [CI: 0.48-1.41]) with DS compared to their respective non-DS comparators. Conclusions: Our study found no overall increased risk of uveitis following a diagnosis of DS compared to a matched control population.


Subject(s)
Down Syndrome , Uveitis , Humans , Down Syndrome/complications , Male , Female , Uveitis/epidemiology , Uveitis/diagnosis , Uveitis/etiology , Child , Retrospective Studies , Child, Preschool , Adolescent , Infant , Databases, Factual , Incidence , Cohort Studies , Risk Factors , Risk Assessment/methods , Risk Assessment/statistics & numerical data
2.
J Neuroinflammation ; 21(1): 133, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778397

ABSTRACT

Behcet's disease (BD) is a rare but globally distributed vasculitis that primarily affects populations in the Mediterranean and Asian regions. Behcet's uveitis (BU) is a common manifestation of BD, occurring in over two-thirds of the patients. BU is characterized by bilateral, chronic, recurrent, non-granulomatous uveitis in association with complications such as retinal ischemia and atrophy, optic atrophy, macular ischemia, macular edema, and further neovascular complications (vitreous hemorrhage, neovascular glaucoma). Although the etiology and pathogenesis of BU remain unclear, numerous studies reveal that genetic factors (such as HLA-B51), dysregulated immune responses of both the innate and adaptive immune systems, infections (such as streptococcus), and environmental factors (such as GDP) are all involved in its development. Innate immunity, including hyperactivity of neutrophils and γδT cells and elevated NK1/NK2 ratios, has been shown to play an essential role in this disease. Adaptive immune system disturbance, including homeostatic perturbations, Th1, Th17 overaction, and Treg cell dysfunction, is thought to be involved in BU pathogenesis. Treatment of BU requires a tailored approach based on the location, severity of inflammation, and systemic manifestations. The therapy aims to achieve rapid inflammation suppression, preservation of vision, and prevention of recurrence. Systemic corticosteroids combined with other immunosuppressive agents have been widely used to treat BU, and beneficial effects are observed in most patients. Recently, biologics have been shown to be effective in treating refractory BU cases. Novel therapeutic targets for treating BU include the LCK gene, Th17/Treg balance, JAK pathway inhibition, and cytokines such as IL-17 and RORγt. This article summarizes the recent studies on BU, especially in terms of pathogenesis, diagnostic criteria and classification, auxiliary examination, and treatment options. A better understanding of the significance of microbiome composition, genetic basis, and persistent immune mechanisms, as well as advancements in identifying new biomarkers and implementing objective quantitative detection of BU, may greatly contribute to improving the adequate management of BU patients.


Subject(s)
Behcet Syndrome , Uveitis , Humans , Behcet Syndrome/immunology , Behcet Syndrome/therapy , Uveitis/immunology , Uveitis/therapy , Uveitis/etiology , Animals
3.
BMC Ophthalmol ; 24(1): 217, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773506

ABSTRACT

BACKGROUND: Only seven cases of ocular Spiroplasma infection have been reported to date, all presenting as congenital cataracts with concomitant intraocular inflammation. We describe the first case of Spiroplasma infection initially presenting as a corneal infiltrate. CASE PRESENTATION: A 1-month-old girl was referred for a corneal infiltrate in the left eye. She presented in our hospital with unilateral keratouveitis. Examination showed a stromal corneal infiltrate and dense white keratic precipitates in the left eye. Herpetic keratouveitis was suspected and intravenous acyclovir therapy was initiated. Two weeks later, the inflammation in the left eye persisted and was also noticed in the right eye. Acute angle-closure glaucoma and a cataract with dilated iris vessels extending onto the anterior lens capsule developed in the left eye. The inflammation resolved after treatment with azithromycin. Iridectomy, synechiolysis and lensectomy were performed. Bacterial metagenomic sequencing (16 S rRNA) and transmission electron microscopy revealed Spiroplasma ixodetis species in lens aspirates and biopsy. Consequently, a diagnosis of bilateral Spiroplasma uveitis was made. CONCLUSIONS: In cases of congenital cataract with concomitant intraocular inflammation, Spiroplasma infection should be considered. The purpose of this case report is to raise awareness of congenital Spiroplasma infection as a cause of severe keratouveitis, cataract and angle-closure glaucoma in newborns. Performing molecular testing on lens aspirates is essential to confirm diagnosis. Systemic macrolides are suggested as the mainstay of treatment.


Subject(s)
Cataract , Eye Infections, Bacterial , Spiroplasma , Uveitis , Humans , Female , Eye Infections, Bacterial/diagnosis , Eye Infections, Bacterial/microbiology , Eye Infections, Bacterial/complications , Cataract/congenital , Cataract/diagnosis , Cataract/complications , Uveitis/diagnosis , Uveitis/microbiology , Uveitis/complications , Spiroplasma/isolation & purification , Keratitis/diagnosis , Keratitis/microbiology , Infant, Newborn , Anti-Bacterial Agents/therapeutic use , Infant
4.
Int J Pharm ; 657: 124178, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38692499

ABSTRACT

Noninfective uveitis is a major cause of vision impairment, and corticosteroid medication is a mainstay clinical strategy that causes severe side effects. Rapamycin (RAPA), a potent immunomodulator, is a promising treatment for noninfective uveitis. However, because high and frequent dosages are required, it is a great challenge to implement its clinical translation for noninfective uveitis therapy owing to its serious toxicity. In the present study, we engineered an injectable microparticulate drug delivery system based on biodegradable block polymers (i.e., polycaprolactone-poly (ethylene glycol)-polycaprolactone, PCEC) for efficient ocular delivery of RAPA via a subconjunctival injection route and investigated its therapeutic efficacy in an experimental autoimmune uveitis (EAU) rat model. RAPA-PCEC microparticles were fabricated using the emulsion-evaporation method and thoroughly characterized using scanning electron microscopy, fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The formed microparticles exhibited slow in vitro degradation over 28 days, and provided both in vitro and in vivo sustained release of RAPA over 4 weeks. Additionally, a single subconjunctival injection of PCEC microparticles resulted in high ocular tolerance. More importantly, subconjunctival injection of RAPA-PCEC microparticles significantly attenuated the clinical signs of EAU in a dose-dependent manner by reducing inflammatory cell infiltration (i.e., CD45+ cells and Th17 cells) and inhibiting microglial activation. Overall, this injectable microparticulate system may be promising vehicle for intraocular delivery of RAPA for the treatment of noninfective uveitis.


Subject(s)
Polyesters , Polyethylene Glycols , Sirolimus , Uveitis , Animals , Uveitis/drug therapy , Sirolimus/administration & dosage , Polyethylene Glycols/chemistry , Polyethylene Glycols/administration & dosage , Polyesters/chemistry , Polyesters/administration & dosage , Rats, Inbred Lew , Rats , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/chemistry , Female , Drug Liberation , Delayed-Action Preparations , Microspheres , Disease Models, Animal , Drug Delivery Systems , Conjunctiva/drug effects , Autoimmune Diseases/drug therapy , Drug Carriers/chemistry , Injections, Intraocular
6.
Pediatr Rheumatol Online J ; 22(1): 50, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693550

ABSTRACT

BACKGROUND: This study investigates the incidence of ocular involvement in Kawasaki disease (KD) and evaluates the relationship between ocular manifestations, laboratory findings, echocardiographic findings, and intravenous immunoglobulin (IVIG) resistance. METHODS: We conducted a cross-sectional study with 58 KD patients from June 2021 to March 2023. For all patients, a complete ophthalmologic examination and echocardiography were performed in the acute phase before starting the treatment. We analyzed the age, sex, mean of white blood cell (WBC) count, platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), echocardiographic findings and IVIG responses for all patients and compared the group with ocular involvement with the group without involvement. RESULTS: The incidence of bilateral acute conjunctivitis was 70.7%, while that of acute uveitis was 30%. Patients with uveitis had significantly higher rates of Coronary artery dilatation and IVIG resistance, as well as higher mean levels of WBC, platelet, and CRP compared to those without uveitis. (P < 0.05). Additionally, the age of patients with uveitis involvement was lower than those without involvement. No significant relationships existed between ESR, AST, or ALT values and uveitis (P > 0.05). Furthermore, no significant correlations existed between any examined items and acute bilateral conjunctivitis. CONCLUSION: Uveitis in KD is significantly associated with coronary artery dilatation, IVIG resistance, higher WBC count, platelet count, and CRP level.


Subject(s)
Drug Resistance , Echocardiography , Immunoglobulins, Intravenous , Mucocutaneous Lymph Node Syndrome , Humans , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/physiopathology , Immunoglobulins, Intravenous/therapeutic use , Male , Female , Cross-Sectional Studies , Echocardiography/methods , Child, Preschool , Infant , Child , Uveitis/etiology , Uveitis/epidemiology , Conjunctivitis/etiology , Conjunctivitis/epidemiology , Incidence , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Blood Sedimentation , Leukocyte Count , Immunologic Factors/therapeutic use , Platelet Count
7.
Med Sci Monit ; 30: e943240, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38711247

ABSTRACT

Behçet uveitis poses significant management challenges, owing to its intricate pathogenesis and the severe prognosis it harbors, frequently culminating in irreversible visual impairment and an elevated risk of blindness. This review synthesizes contemporary insights into personalized immunosuppressive strategies for Behçet uveitis, emphasizing the necessity for a customized approach in recognition of the disease's heterogeneity and the variable responsiveness to treatment. This discourse elaborates on the application, efficacy, and safety profiles of traditional immunosuppressants, highlighting a paradigm shift toward integrative combination therapies aimed at diminishing reliance on glucocorticoids and mitigating their associated adverse effects. This thorough evaluation seeks to enlighten clinical practices and spearhead future investigations aimed at refining the management of Behçet uveitis, championing a personalized, multidisciplinary strategy to amplify therapeutic efficacy and enhance patient quality of life.


Subject(s)
Behcet Syndrome , Immunosuppressive Agents , Uveitis , Humans , Behcet Syndrome/drug therapy , Behcet Syndrome/therapy , Behcet Syndrome/immunology , Uveitis/immunology , Uveitis/drug therapy , Uveitis/therapy , Immunosuppressive Agents/therapeutic use , Precision Medicine/methods , Quality of Life
8.
J Neuroinflammation ; 21(1): 136, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802924

ABSTRACT

Autoimmune uveitis is a leading cause of severe vision loss, and animal models provide unique opportunities for studying its pathogenesis and therapeutic strategies. Here we employ scRNA-seq, RNA-seq and various molecular and cellular approaches to characterize mouse models of classical experimental autoimmune uveitis (EAU), revealing that EAU causes broad retinal neuron degeneration and marker downregulation, and that Müller glia may act as antigen-presenting cells. Moreover, EAU immune response is primarily driven by Th1 cells, and results in dramatic upregulation of CC chemokines, especially CCL5, in the EAU retina. Accordingly, overexpression of CCR5, a CCL5 receptor, in mesenchymal stem cells (MSCs) enhances their homing capacity and improves their immunomodulatory outcomes in preventing EAU, by reducing infiltrating T cells and activated microglia and suppressing Nlrp3 inflammasome activation. Taken together, our data not only provide valuable insights into the molecular characteristics of EAU but also open an avenue for innovative MSC-based therapy.


Subject(s)
Mesenchymal Stem Cells , Mice, Inbred C57BL , Receptors, CCR5 , Single-Cell Analysis , Uveitis , Animals , Mice , Mesenchymal Stem Cells/metabolism , Uveitis/immunology , Receptors, CCR5/metabolism , Receptors, CCR5/genetics , Autoimmune Diseases/therapy , Gene Expression Profiling , Disease Models, Animal , Female , Single-Cell Gene Expression Analysis
9.
Indian J Ophthalmol ; 72(6): 869-877, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38804803

ABSTRACT

PURPOSE: Leptospirosis is a waterborne zoonotic disease prevalent in tropical regions, causing significant morbidity and mortality. It can involve any organ in its primary stage, and uveitis is its late complication. While advanced laboratory diagnosis is available only in tertiary care centers globally, a cost-effective bedside assessment of clinical signs and their scoring could offer a provisional diagnosis. AIM: To analyze the diagnostic potential of demographic and clinical signs in a large cohort of serologically confirmed leptospiral uveitis patients. METHODS: In this retrospective study, demographic and clinical parameters of 876 seropositive leptospiral uveitis patients and 1042 nonleptospiral uveitis controls were studied. Multivariable logistic regression analysis with bootstrap confidence interval (CI) characterized the diagnostic predictors. The performance of the model was evaluated using the area under the receiver operating curve (AUROC). RESULTS: Presence of nongranulomatous uveitis (odds ratio [OR] = 6.9), hypopyon (OR = 4.6), vitreous infiltration with membranous opacities (OR = 4.3), bilateral involvement (OR = 4), panuveitis (OR = 3.3), vasculitis (OR = 1.9), disc hyperemia (OR = 1.6), absence of retinochoroiditis (OR = 15), and absence of cystoid macular edema (OR = 8.9) emerged as predictive parameters. The AUROC value was 0.86 with 95% CI of 0.846-0.874. At a cut-off score of 40, the sensitivity and specificity were 79.5 and 78.4, respectively. CONCLUSION: The study demonstrates that ocular signs can serve as diagnostic predictors for leptospiral uveitis, enabling primary care ophthalmologists to make bedside diagnosis. This can be further confirmed by laboratory methods available at tertiary care centers.


Subject(s)
Eye Infections, Bacterial , Leptospira , Leptospirosis , Uveitis , Humans , Retrospective Studies , Leptospirosis/diagnosis , Leptospirosis/epidemiology , Male , Female , Eye Infections, Bacterial/diagnosis , Eye Infections, Bacterial/epidemiology , Eye Infections, Bacterial/microbiology , Uveitis/diagnosis , Uveitis/microbiology , Uveitis/epidemiology , Adult , Leptospira/isolation & purification , Middle Aged , ROC Curve , Young Adult , Adolescent
10.
Harefuah ; 163(5): 305-309, 2024 May.
Article in Hebrew | MEDLINE | ID: mdl-38734944

ABSTRACT

INTRODUCTION: Ocular inflammation, uveitis, represents over 40 distinct diseases, caused by infectious or non-infectious etiologies. Non-infectious uveitis may be related to systemic autoimmune diseases. Most uveitis patients are of working age, and prolonged disease may affect their independence and ability to work. Uveitis has various clinical manifestations and may result in the development of ocular complications and vision loss. Uveitis accounts for 10-15% of blindness in the developed world. Autoimmune diseases are increasing globally and often involve the eyes. Most cases occur in young active people and therefore any ocular changes have a longer effect. Symptoms may be mild but they might be severe, even blindness. It accounts for 10% to 15% of all causes of blindness among people of working age in the developed world. OBJECTIVES: To describe the ocular manifestation of uveitis related to systemic autoimmune diseases. We will describe ocular signs related to the disease and discuss the treatment approach to prevent the development of ocular complications and vision loss. METHODS: Review of clinical findings and treatment approach to non-infectious uveitis. CONCLUSIONS: Ocular involvement is commonly found in many autoimmune diseases. The severity of ocular disease varies between cases and complications may result in vision loss. Early diagnosis and treatment may prevent the development of ocular complications, maintaining visual acuity and patient independence.


Subject(s)
Autoimmune Diseases , Uveitis , Visual Acuity , Humans , Autoimmune Diseases/diagnosis , Uveitis/etiology , Uveitis/diagnosis , Blindness/etiology , Severity of Illness Index , Early Diagnosis
11.
Ann Med ; 56(1): 2352019, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38747459

ABSTRACT

PURPOSE: To offer consensus on the utilization of corticosteroids (CS) for treating non-infectious uveitis in the context of clinical practice in Taiwan. This entails examining the different administration methods, their advantages and disadvantages, and considering alternative treatments according to the prevailing evidence and health policies. METHODS: Ten ophthalmologists and one rheumatologist convened on December 11, 2022, to review and discuss literature on the topic. The databases explored were the Central Cochrane library, EMBASE, Medline, PUBMED, and Web of Science using relevant keywords. The search spanned from January 1996 to June 2023. After the initial results of the literature review were presented, open voting determined the final statements, with a statement being accepted if it secured more than 70% agreement. This consensus was then presented at significant meetings for further discussions before the final version was established. RESULTS: A flow chart and nine statements emerged from the deliberations. They address the importance of CS in uveitis management, guidelines for using topical CS, indications for both periocular or intravitreal and systemic therapies, and tapering and discontinuation methods for both topical and systemic CS. CONCLUSION: While CS are a cornerstone for non-infectious uveitis treatment, their administration requires careful consideration, depending on the clinical situation and the specific type of uveitis. The consensus generated from this article provides a guideline for practitioners in Taiwan, taking into account local health policies and the latest research on the subject. It emphasizes the significance of strategic tapering, the potential for alternative therapies, and the importance of patient-centric care.


Subject(s)
Adrenal Cortex Hormones , Consensus , Uveitis , Humans , Uveitis/drug therapy , Taiwan , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/administration & dosage
12.
BMJ Open Ophthalmol ; 9(1)2024 May 15.
Article in English | MEDLINE | ID: mdl-38754892

ABSTRACT

BACKGROUND/AIMS: Lipid profiles have been changed in numerous chronic conditions. The impact of uveitis on lipid metabolism remains unclear. METHODS: This is a cross-sectional study included 416 patients with non-infectious uveitis (NIU) and 416 healthy subjects. Standard techniques were used to measure total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDLc), low-density lipoprotein-cholesterol (LDLc) levels. Quantitative optical coherence tomography angiography (OCTA) parameters were obtained from 500 eyes in each group. Correlation analysis examined the relationship between lipid profile and OCTA parameters. RESULTS: Patients with NIU exhibited significantly elevated TC, TG and LDLc levels compared with controls (p=0.003; p<0.001; p<0.001, respectively). Subgroup analysis revealed that HDLc was significantly lower in Behçet's disease (p=0.024) compared with controls. Vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris and optic disk were significantly decreased in NIU eyes (p<0.05, respectively) compared with controls. HDLc exhibited a significant negative correlation with VDs in the whole and parafovea SCP (r=-0.489, p=0.008; r=-0.480, p=0.0026, respectively), while LDLc showed a significant positive correlation with VDs in the whole and parafovea DCP in NIU patients (r=0.576, p=0.032; r=0.267, p=0.034, respectively). CONCLUSIONS: The lipid profile is altered in NIU, and there are correlations between HDLc and LDLc levels and VD as measured by OCTA. Lipid profile analysis may offer valuable insights into evaluating vascular and metabolic aspects of NIU.


Subject(s)
Fluorescein Angiography , Lipids , Tomography, Optical Coherence , Uveitis , Humans , Cross-Sectional Studies , Male , Uveitis/diagnostic imaging , Uveitis/blood , Female , Adult , Fluorescein Angiography/methods , Lipids/blood , Middle Aged , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Fundus Oculi , Lipid Metabolism , Triglycerides/blood
13.
Wiad Lek ; 77(3): 445-449, 2024.
Article in English | MEDLINE | ID: mdl-38691785

ABSTRACT

OBJECTIVE: Aim: To analyze the data and evaluate the prevalence of ocular lesions in patients with moderate ulcerative colitis. PATIENTS AND METHODS: Materials and Methods: We observed 112 patients aged 18-75 years old with clinically, endoscopically and histologically confirmed moderate ulcerative colitis which lasted at least 6 months. An ophthalmologic exam was performed to determine the presence of ocular symptoms. RESULTS: Results: Of the 112 patients with moderate ulcerative colitis, 21 (18,75%) had the following ocular lesions: episcleritis - 7 patients (6,25%), keratopathy - 5 patients (4,46%), uveitis - 5 patients (4,46%), cataract - 2 (1,78%) and scleritis - 2 (1.78%). CONCLUSION: Conclusions: Because ocular symptoms in patients with UC are often nonspecific, it may be beneficial to perform ophthalmologic examinations as a routine follow-up component of in such patients.


Subject(s)
Colitis, Ulcerative , Humans , Colitis, Ulcerative/complications , Colitis, Ulcerative/epidemiology , Adult , Middle Aged , Male , Female , Aged , Young Adult , Adolescent , Prevalence , Scleritis/etiology , Scleritis/epidemiology , Uveitis/etiology , Uveitis/epidemiology , Eye Diseases/etiology , Eye Diseases/epidemiology
14.
Stem Cell Res Ther ; 15(1): 149, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783393

ABSTRACT

BACKGROUND: Autoimmune uveitis is an inflammatory disease triggered by an aberrant immune response. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) are emerging as potential therapeutic agents for this condition. CD73, an ectoenzyme present on MSC-sEVs, is involved in mitigating inflammation by converting extracellular adenosine monophosphate into adenosine. We hypothesize that the inhibitory effect of MSC-sEVs on experimental autoimmune uveitis (EAU) could be partially attributed to the surface expression of CD73. METHODS: To investigate novel therapeutic approaches for autoimmune uveitis, we performed lentiviral transduction to overexpress CD73 on the surface of MSC-sEVs, yielding CD73-enriched MSC-sEVs (sEVs-CD73). Mice with interphotoreceptor retinoid-binding protein (IRBP)-induced EAU were grouped randomly and treated with 50 µg MSC-sEVs, vector infected MSC-sEVs, sEVs-CD73 or PBS via single tail vein injection. We evaluated the clinical and histological features of the induced mice and analyzed the proportion and functional capabilities of T helper cells. Furthermore, T-cells were co-cultured with various MSC-sEVs in vitro, and we quantified the resulting inflammatory response to assess the potential therapeutic benefits of sEVs-CD73. RESULTS: Compared to MSC-sEVs, sEVs-CD73 significantly alleviates EAU, leading to reduced inflammation and diminished tissue damage. Treatment with sEVs-CD73 results in a decreased proportion of Th1 cells in the spleen, draining lymph nodes, and eyes, accompanied by an increased proportion of regulatory T-cells (Treg cells). In vitro assays further reveal that sEVs-CD73 inhibits T-cell proliferation, suppresses Th1 cells differentiation, and enhances Treg cells proportion. CONCLUSION: Over-expression of CD73 on MSC-sEVs enhances their immunosuppressive effects in EAU, indicating that sEVs-CD73 has the potential as an efficient immunotherapeutic agent for autoimmune uveitis.


Subject(s)
5'-Nucleotidase , Autoimmune Diseases , Extracellular Vesicles , Mesenchymal Stem Cells , Uveitis , Animals , Uveitis/pathology , Uveitis/therapy , Uveitis/metabolism , Uveitis/immunology , 5'-Nucleotidase/metabolism , 5'-Nucleotidase/genetics , Extracellular Vesicles/metabolism , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/immunology , Mice , Autoimmune Diseases/therapy , Autoimmune Diseases/pathology , Autoimmune Diseases/immunology , Mice, Inbred C57BL , Disease Models, Animal , Female , Retinol-Binding Proteins , Humans
15.
Biomaterials ; 309: 122617, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38788457

ABSTRACT

Effectively addressing retinal issues represents a pivotal aspect of blindness-related diseases. Novel approaches involving reducing inflammation and rebalancing the immune response are paramount in the treatment of these conditions. This study delves into the potential of a nanogel system comprising polyethylenimine-benzene boric acid-hyaluronic acid (PEI-PBA-HA). We have evaluated the collaborative impact of cerium oxide nanozyme and chemokine CX3CL1 protein for targeted immunomodulation and retinal protection in uveitis models. Our nanogel system specifically targets the posterior segment of the eyes. The synergistic effect in this area reduces oxidative stress and hampers the activation of microglia, thereby alleviating the pathological immune microenvironment. This multifaceted drug delivery system disrupts the cycle of oxidative stress, inflammation, and immune response, suppressing initial immune cells and limiting local retinal structural damage induced by excessive immune reactions. Our research sheds light on interactions within retinal target cells, providing a promising avenue for the development of efficient and innovative drug delivery platforms.


Subject(s)
Cerium , Chemokine CX3CL1 , Nanogels , Uveitis , Animals , Cerium/chemistry , Cerium/pharmacology , Uveitis/drug therapy , Nanogels/chemistry , Chemokine CX3CL1/metabolism , Rats , Retina/drug effects , Retina/metabolism , Immunomodulation/drug effects , Disease Models, Animal , Polyethyleneimine/chemistry , Oxidative Stress/drug effects , Hyaluronic Acid/chemistry , Male , Polyethylene Glycols
16.
Transl Vis Sci Technol ; 13(5): 15, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38767904

ABSTRACT

Purpose: To highlight the utility of en face swept-source optical coherence tomography angiography (SS-OCTA) in assessing vitreoretinal interface cells (VRICs) of patients with active uveitis and their dynamics. Methods: In this prospective, single-center study, 20 eyes from patients with active uveitis were analyzed using six 6 × 6-mm macular scans at three time points: active inflammation (baseline), clinically improving (T1), and resolved inflammation (T2). VRICs were visualized using 3-µm en face OCT slabs on the inner limiting membrane. The variation of VRIC number, density, and size over time was assessed, and VRIC measurements were compared with clinical grading. Results: At baseline, the VRIC count was significantly higher (552.5 VRICs) than that of the healthy controls (478.2 VRICs), with a density of 15.3 cells/mm2. VRIC number decreased significantly to 394.8 (P = 0.007) at T1, with a density of 10.9 cells/mm2 (P = 0.007). VRIC size reduced from 6.8 µm to 6.3 µm at T1 (P = 0.009) and remained stable at T2 (P = 0.3). Correlation coefficients between inflammatory parameters (anterior chamber cells and National Eye Institute vitreous haze), and VRIC count indicated a positive correlation at baseline (r = 0.53), weakening at T1 (r = 0.36), and becoming negative at T2 (r = -0.24). Conclusions: En face SS-OCTA revealed increased VRIC number and size in active uveitis, likely due to monocyte recruitment. Post-inflammation control, VRIC number, size, and density significantly decreased, returning to normal despite residual anterior chamber cells or vitreous haze. Translational Relevance: Visualization of VRICs by in vivo OCT opens up new opportunities for therapeutic targets.


Subject(s)
Tomography, Optical Coherence , Uveitis , Vitreous Body , Humans , Male , Prospective Studies , Female , Uveitis/drug therapy , Uveitis/pathology , Middle Aged , Adult , Vitreous Body/pathology , Vitreous Body/diagnostic imaging , Fluorescein Angiography/methods , Aged , Retina/pathology , Retina/diagnostic imaging , Young Adult , Cell Count , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/administration & dosage
17.
J Med Virol ; 96(5): e29653, 2024 May.
Article in English | MEDLINE | ID: mdl-38712746

ABSTRACT

The magnitude of the effect of human T-lymphotropic virus 1 (HTLV-1) infection on uveitis remains unclear. We conducted a cross-sectional study in a highly endemic area of HTLV-1 in Japan. The study included 4265 residents (men, 39.2%), mostly middle-aged and older individuals with a mean age of 69.9 years, who participated in our surveys between April 2016 and September 2022. We identified HTLV-1 carriers by screening using chemiluminescent enzyme immunoassays and confirmatory tests, and the proportion of carriers was 16.1%. Participants with uveitis were determined from the medical records of all hospitals and clinics where certified ophthalmologists practiced. We conducted logistic regression analyses in an age- and sex-adjusted model to compute the odds ratio (OR) and 95% confidence interval (CI) of uveitis according to HTLV-1 infection status. Thirty-two (0.8%) participants had uveitis. For HTLV-1 carriers, the age- and sex-adjusted OR (95% CI) of uveitis was 3.27 (1.57-6.72) compared with noncarriers. In conclusion, HTLV-1 infection was associated with a higher risk of uveitis among mostly middle-aged and older Japanese residents in a highly endemic HTLV-1 area. Our findings suggest that physicians who treat HTLV-1 carriers should assess ocular symptoms, and those who diagnose patients with uveitis should consider HTLV-1 infection.


Subject(s)
Carrier State , HTLV-I Infections , Human T-lymphotropic virus 1 , Uveitis , Humans , Female , Male , Japan/epidemiology , Uveitis/epidemiology , Uveitis/virology , HTLV-I Infections/epidemiology , Cross-Sectional Studies , Aged , Middle Aged , Prevalence , Human T-lymphotropic virus 1/isolation & purification , Carrier State/epidemiology , Carrier State/virology , Adult , Aged, 80 and over , Endemic Diseases , Young Adult
18.
FASEB J ; 38(7): e23607, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38581245

ABSTRACT

Pathogenic Th17 cells play a crucial role in autoimmune diseases like uveitis and its animal model, experimental autoimmune uveitis (EAU). Dimethyl itaconate (DMI) possesses potent anti-inflammatory effects. However, there is still a lack of knowledge about the role of DMI in regulating pathogenic Th17 cells and EAU. Here, we reported that intraperitoneal administration of DMI significantly inhibited the severity of EAU via selectively suppressing Th17 cell responses. In vitro antigen stimulation studies revealed that DMI dramatically decreased the frequencies and function of antigen-specific Th17, but not Th1, cells. Moreover, DMI hampered the differentiation of naive CD4+ T cells toward pathogenic Th17 cells. DMI-treated DCs produced less IL-1ß, IL-6, and IL-23, and displayed an impaired ability to stimulate antigen-specific Th17 activation. Mechanistically, DMI activated the NRF2/HO-1 pathway and suppressed STAT3 signaling, which subsequently restrains p-STAT3 nuclear translocation, leading to decreased pathogenic Th17 cell responses. Thus, we have identified an important role for DMI in regulating pathogenic Th17 cells, supporting DMI as a promising therapy in Th17 cell-driven autoimmune diseases including uveitis.


Subject(s)
Autoimmune Diseases , Succinates , Uveitis , Animals , Mice , Th17 Cells , NF-E2-Related Factor 2/metabolism , Inflammation/metabolism , Autoimmune Diseases/metabolism , Disease Models, Animal , Mice, Inbred C57BL , Th1 Cells
19.
Zhonghua Yan Ke Za Zhi ; 60(4): 359-369, 2024 Apr 11.
Article in Chinese | MEDLINE | ID: mdl-38583060

ABSTRACT

Objective: To analyze the current research status of uveitis in China. Methods: It was a bibliometric analysis study. Using search formulas covering uveitis and its multiple subtypes, uveitis-related literature in English with publication dates from 2013 to 2022 was retrieved in Web of Science core databases through certain search strategies. This study used the latent Dirichlet allocation (LDA) algorithm to build topic models and analyzed the trends of research topics in recent years. Bibliometric analysis was used to analyze and visualize the bibliometric indicators (e.g., number of publications, citations, and H-index) of the included literature using tools such as VOSviewer software. Results: Over the past decade, China has published 1 657 papers on uveitis, ranking second globally. However, there is still room for improvement in terms of the H-index (58) and citation (12.28 per publication). Countries such as the USA (43.04%) and the United Kingdom (62.54%) were engaged in more international collaboration. We identified ten optimal LDA topics for uveitis literature in China such as immunotherapy, Behçet's disease, and Vogt-Koyanagi-Harada syndrome. Research on uveitis in China was mostly published in Ocular Immunology and Inflammation (92). Conclusions: China has made remarkable progress in uveitis research. Nonetheless, there is still untapped potential to enhance our global academic influence. It is encouraged to promote international collaborations, harness our expertise in areas like Behçet's disease and VKH syndrome, and publish our scientific achievements in high-impact journals.


Subject(s)
Behcet Syndrome , Uveitis , Uveomeningoencephalitic Syndrome , Humans , Bibliometrics , China
20.
PLoS One ; 19(4): e0302295, 2024.
Article in English | MEDLINE | ID: mdl-38635732

ABSTRACT

PURPOSE: This study investigates the visual outcomes of neovascular age-related macular degeneration (nAMD) patients who developed intraocular inflammation (IOI) after intravitreal brolucizumab injection (IVBr). METHODS: We studied 285 eyes of 279 cases diagnosed with nAMD and focused on 18 eyes (6.3%) of 17 cases which developed IOI after IVBr. IVBr was performed either on the initial treatment or for switching of other anti-vascular endothelial growth factor agents during January 2020 to December 2021. We evaluated clinical features and the course of treatment of a 6-month follow-up after IOI occurred. RESULTS: Of 17 cases, 9 cases were male, 8 cases were female. Baseline logarithm of the minimum angle of resolution(logMAR) best-corrected visual acuity (BCVA) was 0.36, BCVA before IOI occurred was 0.30, and BCVA when IOI occurred was 0.43. 16 eyes (88.9%) had symptoms such as visual loss or floaters when IOI occurred. On the other hand, the remaining 2 eyes (11.1%) had no symptoms. 11 eyes (61.1%) had only IOI, while the remaining 7 eyes (38.9%) had IOI and perivascular sheathing. Steroid sub-tenon injection was performed on 1 eye (5.6%), steroid eye drops were used in 11 eyes (61.1%), and 6 eyes (33.3%) were followed-up without treatment. Neovascular AMD recurred in 16 eyes (88.9%) after IOI occurred and were treated with aflibercept. VA at 3 and 6 months after IOI occurred were significantly improved to 0.34 and 0.30, respectively (P = 0.09 at 3 months and P = 0.02 at 6 months). The symptoms of patients were improved in all cases. We were able to stop steroid treatment in all cases. CONCLUSIONS: IOI occurred in 6.3% of nAMD patients after IVBr treatment. All of which showed significant improvement from logMAR of 0.43 to 0.30 with steroid treatment or without any treatment. We should consider the possibility of IOI after IVBr as a complication, however, they have a relatively good prognosis if treated at an early stage.


Subject(s)
Antibodies, Monoclonal, Humanized , Uveitis , Wet Macular Degeneration , Humans , Female , Male , Angiogenesis Inhibitors/adverse effects , Japan , Vascular Endothelial Growth Factor A , Visual Acuity , Wet Macular Degeneration/drug therapy , Inflammation/drug therapy , Intravitreal Injections , Steroids , Receptors, Vascular Endothelial Growth Factor
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