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1.
Stem Cell Res Ther ; 15(1): 149, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783393

RESUMO

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.


Assuntos
5'-Nucleotidase , Doenças Autoimunes , Vesículas Extracelulares , Células-Tronco Mesenquimais , Uveíte , Animais , Uveíte/patologia , Uveíte/terapia , Uveíte/metabolismo , Uveíte/imunologia , 5'-Nucleotidase/metabolismo , 5'-Nucleotidase/genética , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/imunologia , Camundongos , Doenças Autoimunes/terapia , Doenças Autoimunes/patologia , Doenças Autoimunes/imunologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Feminino , Proteínas de Ligação ao Retinol , Humanos
2.
J Neuroinflammation ; 21(1): 133, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778397

RESUMO

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.


Assuntos
Síndrome de Behçet , Uveíte , Humanos , Síndrome de Behçet/imunologia , Síndrome de Behçet/terapia , Uveíte/imunologia , Uveíte/terapia , Uveíte/etiologia , Animais
3.
Expert Rev Mol Med ; 26: e9, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618935

RESUMO

Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and mechanisms but share a multifactorial and complex nature, making their management challenging and burdensome for patients and clinicians. Furthermore, the lack of symptoms in the early stages of glaucoma and the diverse aetiology of uveitis hinder timely and accurate diagnoses, which are a cause of poor visual outcomes under both conditions. Although current treatment is effective in most cases, it is often associated with low patient adherence and adverse events, which directly impact the overall therapeutic success. Therefore, long-lasting alternatives with improved safety and efficacy are needed. Gene therapy, particularly utilising adeno-associated virus (AAV) vectors, has emerged as a promising approach to address unmet needs in these diseases. Engineered capsids with enhanced tropism and lower immunogenicity have been proposed, along with constructs designed for targeted and controlled expression. Additionally, several pathways implicated in the pathogenesis of these conditions have been targeted with single or multigene expression cassettes, gene editing and silencing approaches. This review discusses strategies employed in AAV-based gene therapies for glaucoma and non-infectious uveitis and provides an overview of current progress and future directions.


Assuntos
Glaucoma , Uveíte , Humanos , Glaucoma/genética , Glaucoma/terapia , Uveíte/genética , Uveíte/terapia , Olho , Cegueira , Terapia Genética
4.
Indian J Ophthalmol ; 72(6): 809-815, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38454865

RESUMO

Uveitis and its complications are more common in the developing world, in which the condition occurs in up to 714 per 100,000 in the population and accounts for up to 25% of all blindness. In India, the ophthalmic sub speciality of uveitis greatly evolved in the last four decades. In the early decades most of the studies were epidemiological studies. In recent years, more research has been published due to tremendous advancements in clinical diagnosis, laboratory investigations and ancillary test and treatment modalities. In this review article, we did a medline search with key words 'uveitis' and 'India', and selectively incorporated articles showing the evolution of this sub-speciality in India.


Assuntos
Uveíte , Humanos , Índia/epidemiologia , Uveíte/diagnóstico , Uveíte/epidemiologia , Uveíte/terapia , Pesquisa Biomédica/tendências , Gerenciamento Clínico , Oftalmologia
5.
Zhonghua Yan Ke Za Zhi ; 60(3): 289-295, 2024 Mar 11.
Artigo em Chinês | MEDLINE | ID: mdl-38462380

RESUMO

Adeno-associated virus (AAV) vectors have been widely employed in gene therapy for ocular and systemic diseases. However, clinical trial outcomes have indicated that gene therapy may trigger severe adverse events associated with immune-inflammatory reactions, thereby impacting the safety and efficacy of gene therapy. The immune-inflammatory reaction induced after gene therapy in the eye is referred to as gene therapy-associated uveitis, which has become a major obstacle limiting the long-term and effective use of ocular gene therapy. This review comprehensively explores four aspects: the immune response mechanisms of gene therapy, ocular manifestations of associated uveitis, factors influencing immune inflammation, and preventive and therapeutic strategies. The aim is to provide insights for the development of safer and more effective ocular gene therapy.


Assuntos
Dependovirus , Uveíte , Humanos , Dependovirus/genética , Vetores Genéticos , Terapia Genética , Uveíte/terapia , Imunidade
6.
Artigo em Inglês | MEDLINE | ID: mdl-37037600

RESUMO

The underlying immune state of inherited retinal degenerations (IRDs) and retinitis pigmentosa (RP) has been an emerging area of interest, wherein the consequences have never been greater given the widespread recognition of gene therapy-associated uveitis (GTU) in gene therapy clinical trials. Whereas some evidence suggests that the adaptive immune system may play a role, the majority of studies indicate that the innate immune system is likely the primary driver of neuroinflammation in RP. During retinal degeneration, discrete mechanisms activate resident microglia and promote infiltrating macrophages that can either be protective or detrimental to photoreceptor cell death. This persistent stimulation of innate immunity, overlaid by the introduction of viral antigens as part of gene therapy, has the potential to trigger a complex microglia/macrophage-driven proinflammatory state. A better understanding of the immune pathophysiology in IRD and GTU will be necessary to improve the success of developing novel treatments for IRDs.


Assuntos
Degeneração Retiniana , Retinose Pigmentar , Uveíte , Humanos , Retinose Pigmentar/genética , Retinose Pigmentar/terapia , Macrófagos , Terapia Genética , Uveíte/genética , Uveíte/terapia
7.
Eur J Pharmacol ; 960: 176139, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38059448

RESUMO

Autoimmune uveitis is an intraocular inflammatory disease with a high blindness rate in developed countries such as the United States. It is pressing to comprehend the pathogenesis of autoimmune uveitis and develop novel schemes for its treatment. In the present research, we demonstrated that the Notch signaling pathway was activated, and the level of miR-223-3p was significantly reduced in rats with experimental autoimmune uveitis (EAU) compared with the level of normal rats. To investigate the relationship between miR-223-3p and Notch signaling, EAU rats received miR-223-3p-carrying lentivirus, miR-223-3p vector-carrying lentivirus (miR-223-3p-N), and γ-secretase inhibitor (DAPT), respectively. The results of Q-PCR, immunological experiments, and flow cytometry analysis all support the hypothesis that both miR-223-3p and DAPT, a Notch signaling pathway inhibitor, had similar inhibitory effects on the EAU pathological process. That is to say, they could both inhibit the activation of the Notch signaling pathway via modulating recombination signal binding protein-Jκ (RBPJ) to restore the polarization imbalance of M/M2 macrophages in EAU rats. In addition, miR-223-3p could also inhibit NLRP3 inflammasome activation and inflammasome-induced pyroptosis in ocular tissues. Taken together, our findings indicate that miR-223-3p serves as an important regulator in M1 macrophage polarization and pyroptosis, thereby alleviating the inflammatory response in uveitis.


Assuntos
MicroRNAs , Uveíte , Ratos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Inflamassomos , Piroptose , Uveíte/metabolismo , Uveíte/terapia , Macrófagos/metabolismo , MicroRNAs/genética , Transdução de Sinais
8.
Reumatol Clin (Engl Ed) ; 19(9): 465-477, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37839964

RESUMO

OBJECTIVE: To develop evidence-based expert-consensus recommendations for the management of non-infectious, non-neoplastic, non-demyelinating disease associated uveitis. METHODS: Clinical research questions relevant to the objective of the document were identified, and reformulated into PICO format (patient, intervention, comparison, outcome) by a panel of experts selected based on their experience in the field. A systematic review of the available evidence was conducted, and evidence was graded according to GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. Subsequently, recommendations were developed. RESULTS: Three PICO questions were constructed referring to uveitis anterior, non-anterior and complicated with macular edema. A total of 19 recommendations were formulated, based on the evidence found and/or expert consensus. CONCLUSIONS: Here we present the first official recommendations of the Spanish Society of Rheumatology for the treatment of non-infectious and non-demyelinating disease associated uveitis. They can be directly applied to the Spanish healthcare system as a tool for assistance and therapeutic homogenisation.


Assuntos
Edema Macular , Uveíte , Humanos , Edema Macular/complicações , Uveíte/complicações , Uveíte/terapia , Revisões Sistemáticas como Assunto , Guias de Prática Clínica como Assunto
9.
Vet Clin North Am Equine Pract ; 39(3): 541-552, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37442730

RESUMO

Regenerative therapy and biologics have the promise to treat equine ocular surface diseases, including corneal ulceration or immune-mediated keratitis, or intraocular diseases such as uveitis. The use of blood-derived products such as serum or platelet-rich plasma, mesenchymal stem cells, or amniotic membrane grafts may be beneficial for the treatment of ulcerative and chronic keratitis in horses. Furthermore, the use of stem cells or gene therapy has promise for the treatment of Intraocular diseases such as equine recurrent uveitis by providing efficacious, practical, and long-term therapy for these blinding diseases.


Assuntos
Produtos Biológicos , Doenças dos Cavalos , Ceratite , Oftalmologia , Uveíte , Animais , Cavalos , Produtos Biológicos/uso terapêutico , Doenças dos Cavalos/terapia , Ceratite/veterinária , Uveíte/terapia , Uveíte/veterinária , Células-Tronco
10.
Am J Vet Res ; 83(11)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36201404

RESUMO

This review, which is part of the "Currents in One Health" series, describes the importance of the study of immune-mediated ocular disease in the development of innovative therapeutics, such as cell and gene therapy for the eye. Recent examples of cell and gene therapy studies from the author's laboratory are reviewed to emphasize the importance of One Health initiatives in developing innovative therapies for ocular diseases. Spontaneous immune-mediated corneal disease is common in horses, cats, dogs, and humans. Autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) injected subconjunctivally resulted in the resolution of naturally occurring immune-mediated keratitis (IMMK) without adverse effects. These results support that autologous subconjunctival BM-MSC therapy may be a viable treatment alternative for IMMK. Furthermore, the use of subconjunctival MSCs may be an effective method to treat ocular surface immune-mediated diseases in humans and other species, including herpetic stromal keratitis and immunologic dry eye disease. Furthermore, the use of adeno-associated viral (AAV) vectors to deliver the immunosuppressive transgene cDNA of equine interleukin 10 (eqIL-10) or human leukocyte antigen G injected intravitreally was shown to be safe and inhibited the development of uveitis in the experimental autoimmune uveitis rat model. Efficacy and safety studies of ocular gene therapy in models will pave the way for clinical trials in animals with naturally occurring immune-mediated diseases, such as a therapeutic clinical trial for AAV-eqIL-10 in horses with equine recurrent uveitis.


Assuntos
Doenças do Gato , Doenças do Cão , Doenças dos Cavalos , Ceratite , Células-Tronco Mesenquimais , Doenças dos Roedores , Uveíte , Cavalos , Animais , Humanos , Ratos , Gatos , Cães , Animais Domésticos , Olho , Ceratite/metabolismo , Ceratite/veterinária , Uveíte/terapia , Uveíte/veterinária , Doenças do Cão/metabolismo , Doenças dos Cavalos/terapia , Doenças dos Cavalos/metabolismo , Doenças dos Roedores/metabolismo
11.
Zhonghua Yan Ke Za Zhi ; 58(7): 500-505, 2022 Jul 11.
Artigo em Chinês | MEDLINE | ID: mdl-35796122

RESUMO

Fuchs uveitis syndrome is a chronic, non-granulomatous, and unilateral anterior uveitis. It is one of the most under-diagnosed or misdiagnosed uveitis entities. A number of factors are involved in its etiology, which has not been completely understood. Misdiagnosis of this disease may result in over-treatment and facilitate the development of complicated cataract and secondary glaucoma. An extensive investigation and literature review on this disease have been performed by the experts in the Ocular Immunology Group of Ophthalmology Society of Chinese Medical Association and the Uveitis and Ocular Immunology Group of Chinese Ophthalmologist Association. Consensus opinions on Fuchs uveitis syndrome have been developed in an attempt to provide general guidance and reference in the diagnosis and treatment of this disease.


Assuntos
Iridociclite , Uveíte Anterior , Uveíte , China , Consenso , Humanos , Uveíte/complicações , Uveíte/diagnóstico , Uveíte/terapia
12.
Int J Mol Sci ; 23(13)2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35806031

RESUMO

In the last decades, personalized medicine has been increasing its presence in different fields of medicine, including ophthalmology. A new factor that can help us direct medicine towards the challenge of personalized treatments is the microbiome. The gut microbiome plays an important role in controlling immune response, and dysbiosis has been associated with immune-mediated diseases such as non-infectious uveitis (NIU). In this review, we gather the published evidence, both in the pre-clinical and clinical studies, that support the possible role of intestinal dysbiosis in the pathogenesis of NIU, as well as the modulation of the gut microbiota as a new possible therapeutic target. We describe the different mechanisms that have been proposed to involve dysbiosis in the causality of NIU, as well as the potential pharmacological tools that could be used to modify the microbiome (dietary supplementation, antibiotics, fecal microbiota transplantation, immunomodulators, or biologic drugs) and, consequently, in the control of the NIU. Furthermore, there is increasing scientific evidence suggesting that the treatment with anti-TNF not only restores the composition of the gut microbiota but also that the study of the composition of the gut microbiome will help predict the response of each patient to anti-TNF treatment.


Assuntos
Microbioma Gastrointestinal , Microbiota , Uveíte , Disbiose , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/fisiologia , Humanos , Microbiota/fisiologia , Inibidores do Fator de Necrose Tumoral , Uveíte/terapia
14.
Graefes Arch Clin Exp Ophthalmol ; 260(7): 2079-2086, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35175410

RESUMO

OBJECTIVE: We conducted a systematic review to evaluate the outcome of macular hole (MH) treatment in eyes with uveitis. DATA SOURCE: We searched PubMed and Embase databases from inception through August 15, 2021. STUDY SELECTION: We included eyes with MHs secondary to uveitis that were managed medically or underwent pars plana vitrectomy (PPV). We excluded eyes with idiopathic MH and those secondary to causes other than uveitis. RESULTS: Of 27 articles, we identified 86 eyes with MH secondary to uveitis that received either conservative medical treatment alone or PPV with adequate follow-up. The mean (± SD) age of patients included in this review was 46.6 (± 16.8) years; 60.5% were males. The most common etiology of uveitis was Behçet's disease (34.6%) and toxoplasmosis (19.7%). The most common anatomical location of uveitis was posterior (59.3%) followed by panuveitis (35.2%). The mean (± SD) baseline LogMAR vision was 1.1 (± 0.5). Conservative medical treatment was employed in 34.9%, while PPV was performed in 65.1% of eyes. Overall, the mean (SD) LogMAR vision improved from 1.1 (± 0.5) at baseline to 0.7 (± 0.5) after treatment. Inflammation-related MHs were closed in 40% of eyes after conservative therapy and in 87.5% of eyes after PPV. Visual improvement occurred in most eyes (83.9%) that had successful closure of their MH. CONCLUSIONS: Visual improvement occurs in most eyes that had successful closure of their inflammation-related MH. Conservative medical control of uveitis may lead to closure of inflammation-related MHs and is an important step prior to surgery, if required. Surgical intervention for inflammation-related MHs is associated with good functional and anatomical results.


Assuntos
Perfurações Retinianas , Uveíte , Adulto , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/etiologia , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Uveíte/complicações , Uveíte/diagnóstico , Uveíte/terapia , Acuidade Visual , Vitrectomia/métodos
15.
J Tissue Eng Regen Med ; 16(1): 26-35, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34674378

RESUMO

Mesenchymal stem cells (MSCs) are adult stem cells from mesoderm with multi potential differentiation, and are being widely studied as a promising treatment for autoimmune diseases. The main inflammatory factors of experimental autoimmune uveitis (EAU) are T helper type 1 (Th1) and Th17. Regulatory B cells (Bregs) are a newly designated B cell subgroup, which has been proved to play a key role in regulating inflammation, autoimmunity and cancer. In this regard, we establish the EAU model by injecting interphotoreceptor retinoid-binding protein combined with complete Freund's adjuvant into the tail vein and bilateral thighs of rats, and inject MSCs or equal volume of phosphate buffer saline intraperitoneally on the day of immunization. Dynamic changes of cell subsets and cytokine expression are tested at different time periods to explore the relationship between MSCs treatment and disease prognosis during EAU course. Our results suggest that compared with the model control group, MSCs treatment can significantly reduce the production of Th1 and Th17 cytokines during EAU, while the production of regulatory B cells (Bregs) cytokines is significantly increased. At the same time, MSCs can reduce the proportion of Th17 in lymphocytes while the proportion of Bregs is elevated, thus inhibiting the differentiation and activity of interleukin in EAU rats. All this results provide more powerful evidence for cell therapy of autoimmune uveitis.


Assuntos
Linfócitos B Reguladores , Células-Tronco Mesenquimais , Uveíte , Animais , Linfócitos B Reguladores/metabolismo , Modelos Animais de Doenças , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Células Th1 , Uveíte/metabolismo , Uveíte/terapia
16.
Pediatr Rheumatol Online J ; 19(1): 139, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479590

RESUMO

BACKGROUND: Surgeries for idiopathic uveitis and juvenile idiopathic arthritis-associated uveitis in children are complex because of the high risk of inflammatory postoperative complications. There is no consensus about treatment adaptation during the perioperative period. The objectives of this study are to report the therapeutic changes made in France and to determine whether maintaining or stopping immunosuppressive therapies is associated with an increased risk of surgical site infection or an increased risk of uveitis or arthritis flare-up. METHODS: We conducted a retrospective cohort study between January 1, 2006 and December 31, 2018 in six large University Hospitals in France. Inclusion criteria were chronic idiopathic uveitis or chronic uveitis associated with juvenile idiopathic arthritis under immunosuppressive therapies at the time of the surgical procedure, operated before the age of 16. Data on perioperative treatments, inflammatory relapses and post-operative infections were collected. RESULTS: A total of 76 surgeries (42% cataract surgeries, 30% glaucoma surgeries and 16% posterior capsule opacification surgeries) were performed on 37 children. Adaptation protocols were different in the six hospitals. Immunosuppressive therapies were discontinued in five cases (7%) before surgery. All the children in the discontinuation group had an inflammatory relapse within 3 months after surgery compared to only 25% in the other group. There were no postoperative infections. CONCLUSIONS: The results of this study show varying practices between centres. The benefit-risk balance seems to favour maintaining immunosuppressive therapies during surgery. Further studies are needed to determine the optimal perioperative treatments required to limit post-operative inflammatory relapses.


Assuntos
Artrite Juvenil/complicações , Imunomodulação , Uveíte/etiologia , Uveíte/terapia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , França , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Recidiva , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Exacerbação dos Sintomas , Uveíte/cirurgia
17.
Gac Med Mex ; 157(2): 140-146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34270526

RESUMO

OBJECTIVE: To determine the psychosocial and economic impact suffered by patients diagnosed with uveitis in Mexico. METHODS: Survey in uveitis-diagnosed patients. Demographic data and socioeconomic level were recorded. Symptoms, time to diagnosis, type of treatment, behavior, attitudes and feelings towards the disease were identified. RESULTS: One hundred surveys were conducted in patients with uveitis, who had a mean age of 45 ± 17.08 years, and socioeconomic level ≤ D; 54 were females. Diagnostic delay was 1.87 ± 2.73 years. Annually, patients attend 2.1 ± 2.14 appointments per month, and are admitted once to the emergency department and remain hospitalized for 3.7 days. Patients use systemic treatment with steroidal anti-inflammatory drugs (53 %), immunosuppressant agents (31 %), biological therapy (7 %), topical treatment with lubricants (44 %) or steroids (26 %) and undergo surgery (39 %). Observed comorbidities include hypertension, diabetes mellitus, rheumatoid arthritis (18 %), Sjögren's syndrome, systemic lupus erythematosus, and nonspecific chronic ulcerative colitis. Complications: visual impairment, cataracts and blindness. Uveitis affects their life in 83 % of cases, in 41 % does it daily, and 49 % need care from another person. Seventy-nine percent receive private care and 43 % have social security, with $ 3,590 ± $ 2,730.65 pesos being spent monthly on medicines, transportation, medical appointments and studies. Annually, work absenteeism is 8.5 ± 14.56 days, plus 7.0 days of disability or hospitalization; 51% refer lack of support to learn about the disease. CONCLUSIONS: This is the first national study to portray the condition of patients with uveitis and the shortcomings they go through, including the economic and biopsychosocial fields.


OBJETIVO: Conocer el impacto psicosocial y económico quede la uveítis en México. MÉTODOS: Encuesta en pacientes diagnosticados con uveítis. Se registraron datos demográficos y nivel socioeconómico. Se identificaron síntomas, tiempo al diagnóstico, tratamiento, comportamiento, actitudes y sentimientos ante la enfermedad. RESULTADOS: Se realizaron 100 encuestas a pacientes con uveítis, con edad media de 45 ± 17.08 años, nivel socioeconómico ≤ D; 54 eran mujeres. El diagnóstico se realizó al 1.87 ± 2.73 años. Acuden anualmente a cita 2.1 ± 2.14 mes, más de 1 a urgencias y son hospitalizados 3.7 días. Utilizan tratamiento sistémico con antiinflamatorios esteroideos (53 %), inmunosupresor (31 %), terapia biológica (7 %), tratamiento tópico con lubricantes (44 %), esteroides (26 %) y cirugías (39 %). Comorbilidades observadas: hipertensión arterial, diabetes mellitus, artritis reumatoide (18 %), síndrome de Sjögren, lupus y colitis ulcerativa crónica inespecífica. Complicaciones: deterioro visual, cataratas y ceguera. La uveítis afecta su vida en el 83 % de los casos, en el 41 % a diario y el 49 % necesitan cuidados de otra persona. El 79 % reciben atención privada, el 43 % cuenta con seguridad social, gastando mensualmente $3,590 ± $2,730.65 pesos en medicamentos, transporte, consulta médicas y estudios. Anualmente con ausentismo laboral de 8.5 ± 14.56 días, más 7.0 días de incapacidad u hospitalización. El 51 % refieren falta de apoyo para conocer la enfermedad. CONCLUSIONES: Se trata del primer estudio nacional que escenifica la condición de los pacientes con uveítis y las insuficiencias por las que atraviesan, incluyendo el ámbito económico y biopsicosocial.


Assuntos
Uveíte/economia , Uveíte/psicologia , Atividades Cotidianas , Adulto , Comorbidade , Efeitos Psicossociais da Doença , Diagnóstico Tardio , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Hospitalização , Humanos , Tempo de Internação , Masculino , México , Pessoa de Meia-Idade , Fatores Socioeconômicos , Fatores de Tempo , Uveíte/diagnóstico , Uveíte/terapia
18.
EBioMedicine ; 70: 103496, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34280776

RESUMO

BACKGROUND: Induction of autoantigen-specific Treg cells that suppress tissue-specific autoimmunity without compromising beneficial immune responses is the holy-grail for immunotherapy to autoimmune diseases. METHODS: In a model of experimental autoimmune uveitis (EAU) that mimics human uveitis, ocular inflammation was induced by immunization with retinal antigen interphotoreceptor retinoid-binding protein (IRBP). Mice were given intraperitoneal injection of αCD4 antibody (Ab) after the onset of disease, followed by administration of IRBP. EAU was evaluated clinically and functionally. Splenocytes, CD4+CD25- and CD4+CD25+ T cells were sorted and cultured with IRBP or αCD3 Ab. T cell proliferation and cytokine production were assessed. FINDINGS: The experimental approach resulted in remission of ocular inflammation and rescue of visual function in mice with established EAU. Mechanistically, the therapeutic effect was mediated by induction of antigen-specific Treg cells that inhibited IRBP-driven Th17 response in TGF-ß and IL-10 dependent fashion. Importantly, the Ab-mediated immune tolerance could be achieved in EAU mice by administration of retinal autoantigens, arrestin but not limited to IRBP only, in an antigen-nonspecific bystander manner. Further, these EAU-suppressed tolerized mice did not compromise their anti-tumor T immunity in melanoma model. INTERPRETATION: We successfully addressed a specific immunotherapy of EAU by in vivo induction of autoantigen-specific Treg cells without compromising host overall T cell immunity, which should have potential implication for patients with autoimmune uveitis. FUNDING: This study was supported by the Natural Science Foundation of Guangdong Province and the Fundamental Research Fund of the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center.


Assuntos
Doenças Autoimunes/terapia , Efeito Espectador , Terapia de Imunossupressão/métodos , Linfócitos T Reguladores/imunologia , Uveíte/terapia , Animais , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Linhagem Celular Tumoral , Células Cultivadas , Proteínas do Olho/imunologia , Interleucina-10/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Ligação ao Retinol/imunologia , Fator de Crescimento Transformador beta/metabolismo , Uveíte/imunologia
19.
Gac. méd. Méx ; 157(2): 147-153, mar.-abr. 2021. tab
Artigo em Espanhol | LILACS | ID: biblio-1279094

RESUMO

Resumen Objetivo: Conocer el impacto psicosocial y económico quede la uveítis en México. Métodos: Encuesta en pacientes diagnosticados con uveítis. Se registraron datos demográficos y nivel socioeconómico. Se identificaron síntomas, tiempo al diagnóstico, tratamiento, comportamiento, actitudes y sentimientos ante la enfermedad. Resultados: Se realizaron 100 encuestas a pacientes con uveítis, con edad media de 45 ± 17.08 años, nivel socioeconómico ≤ D; 54 eran mujeres. El diagnóstico se realizó al 1.87 ± 2.73 años. Acuden anualmente a cita 2.1 ± 2.14 mes, más de 1 a urgencias y son hospitalizados 3.7 días. Utilizan tratamiento sistémico con antiinflamatorios esteroideos (53 %), inmunosupresor (31 %), terapia biológica (7 %), tratamiento tópico con lubricantes (44 %), esteroides (26 %) y cirugías (39 %). Comorbilidades observadas: hipertensión arterial, diabetes mellitus, artritis reumatoide (18 %), síndrome de Sjögren, lupus y colitis ulcerativa crónica inespecífica. Complicaciones: deterioro visual, cataratas y ceguera. La uveítis afecta su vida en el 83 % de los casos, en el 41 % a diario y el 49 % necesitan cuidados de otra persona. El 79 % reciben atención privada, el 43 % cuenta con seguridad social, gastando mensualmente $3,590 ± $2,730.65 pesos en medicamentos, transporte, consulta médicas y estudios. Anualmente con ausentismo laboral de 8.5 ± 14.56 días, más 7.0 días de incapacidad u hospitalización. El 51 % refieren falta de apoyo para conocer la enfermedad. Conclusiones: Se trata del primer estudio nacional que escenifica la condición de los pacientes con uveítis y las insuficiencias por las que atraviesan, incluyendo el ámbito económico y biopsicosocial.


Abstract Objective: Determine the psychosocial and economic impact suffered by patients diagnosed with uveitis in Mexico. Methods: Survey in uveitis-diagnosed patients. Demographic data and socioeconomic level were recorded. Symptoms, time to diagnosis, type of treatment, behavior, attitudes and feelings towards the disease were identified. Results: One hundred surveys were conducted in patients with uveitis, who had a mean age of 45 ± 17.08 years, and socioeconomic level ≤ D; 54 were females. Diagnostic delay was 1.87 ± 2.73 years. Annually, patients attend 2.1 ± 2.14 appointments per month, and are admitted once to the emergency department and remain hospitalized for 3.7 days. Patients use systemic treatment with steroidal anti-inflammatory drugs (53 %), immunosuppressant agents (31 %), biological therapy (7 %), topical treatment with lubricants (44 %) or steroids (26 %) and undergo surgery (39 %). Observed comorbidities include hypertension, diabetes mellitus, rheumatoid arthritis (18 %), Sjögren’s syndrome, systemic lupus erythematosus, and nonspecific chronic ulcerative colitis. Complications: visual impairment, cataracts and blindness. Uveitis affects their life in 83 % of cases, in 41 % does it daily, and 49 % need care from another person. Seventy-nine percent receive private care and 43 % have social security, with $ 3,590 ± $ 2,730.65 pesos being spent monthly on medicines, transportation, medical appointments and studies. Annually, work absenteeism is 8.5 ± 14.56 days, plus 7.0 days of disability or hospitalization; 51% refer lack of support to learn about the disease. Conclusions: This is the first national study to portray the condition of patients with uveitis and the shortcomings they go through, including the economic and biopsychosocial fields.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Uveíte/economia , Uveíte/psicologia , Fatores Socioeconômicos , Fatores de Tempo , Uveíte/diagnóstico , Uveíte/terapia , Atividades Cotidianas , Comorbidade , Conhecimentos, Atitudes e Prática em Saúde , Efeitos Psicossociais da Doença , Diagnóstico Tardio , Hospitalização , Tempo de Internação , México
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