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1.
Int Ophthalmol ; 44(1): 149, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502258

RESUMO

PURPOSE: This review aims to summarize the current knowledge concerning the clinical features, diagnostic work-up, and therapeutic approach of bilateral diffuse uveal melanocytic proliferation (BDUMP). METHODS: A meticulous literature search was performed in the PubMed database. A supplementary search was made in Google Scholar to complete the collected items. Our search strategy utilized the following keywords: "bilateral diffuse uveal melanocytic proliferation", "BDUMP", and "Paraneoplastic Syndrome". Articles were considered based on their relevance, with the search spanning publications up to 2023. Studies were excluded if they did not contribute pertinent information or lacked methodological rigor. A critical appraisal of included studies was conducted, assessing study design, sample size, methodology, and potential bias, ensuring a thorough and transparent review process. RESULTS: BDUMP is a rare and potentially sight-threatening condition characterized by the bilateral proliferation of melanocytes within the uvea. BDUMP is typically observed in middle-aged or elderly individuals and is often associated with an underlying malignancy, most commonly of gastrointestinal origin. BDUMP is frequently misdiagnosed as a benign nevus or choroidal metastasis, leading to delayed diagnosis and treatment. The ophthalmic symptoms and signs typically precede the diagnosis of a systemic malignancy, emphasizing the crucial role of ophthalmologists in the recognition of BDUMP. Several diagnostic modalities can aid in the diagnosis of BDUMP, including ophthalmic examination, imaging studies such as optical coherence tomography, fluorescein angiography, and indocyanine green angiography, and biopsy of the uveal tissue. Treatment of BDUMP is directed towards the underlying malignancy and may include chemotherapy, radiotherapy, or surgical resection. Additionally, strict monitoring with regular follow-ups may contribute to the detection of new lesions and the reduction in the size of existing ones. CONCLUSIONS: BDUMP can be considered a potential biomarker in the management of malignancies, especially when the primary underlying tumor has not been detected. Further research is needed to better understand the pathogenesis of BDUMP and its association with malignancy.


Assuntos
Neoplasias da Retina , Úvea , Pessoa de Meia-Idade , Idoso , Humanos , Úvea/patologia , Melanócitos/patologia , Neoplasias da Retina/patologia , Corioide , Proliferação de Células
2.
Clin Lymphoma Myeloma Leuk ; 24(2): e40-e49.e3, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37996265

RESUMO

BACKGROUND: In multiple myeloma (MM), improving our understanding of routine clinical practice and the effectiveness of agents outside of clinical trials is important. TOURMALINE-MM1 data resulted in approval of ixazomib for MM patients who have received ≥ 1 prior therapy. PATIENTS AND METHODS: UVEA-IXA comprised a retrospective chart review in the early access program, and a prospective 1-year follow-up period. Eligible patients had had a biochemical and/or symptomatic relapse after 1-3 prior lines of therapy; no anti-MM therapy for > 3 cycles at the start of ixazomib therapy; and an Eastern Cooperative Oncology Group performance score of 0-2. Lenalidomide- or proteasome inhibitor (PI)-refractory patients were ineligible. Primary endpoints were response and progression-free survival (PFS). RESULTS: Of 357 enrolled patients, 309 were evaluable; most patients received ixazomib alongside lenalidomide (98%) and dexamethasone (97%); 61% had received 2-3 prior lines of therapy. Median PFS was 15.6 months (95% confidence interval [CI]: 12.0-20.6) in all evaluable patients, and 19.6 (95% CI: 12.1-27.0) and 13.9 (95% CI: 10.1-18.1) months in patients who received 1 and ≥ 2 prior lines of therapy, respectively. The overall response rate was 67% in all evaluable patients, and 72% and 63%, respectively, in patients who received 1 and ≥ 2 prior lines of therapy. Median overall survival was 35.5 months. The ixazomib safety profile was consistent with previous reports. CONCLUSION: This study supports ixazomib-based therapy as an effective and tolerable treatment in the real-world. Outcomes were favorable in patients with 1 or ≥ 2 prior lines of therapy who were not lenalidomide- or PI-refractory.


Assuntos
Compostos de Boro , Glicina/análogos & derivados , Mieloma Múltiplo , Humanos , Lenalidomida/uso terapêutico , Estudos Retrospectivos , Estudos Prospectivos , Dexametasona/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Úvea
4.
Eye (Lond) ; 37(13): 2590-2616, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37142776

RESUMO

The uveal vascular bed is the largest vascular system in the eye and has a role in supplying almost every tissue in the eyeball. This makes it the most important ocular vascular system. This is an up-to-date review of the literature of the entire uveal vascular bed in health based on detailed anatomy of the posterior ciliary arteries (PCAs), anterior ciliary arteries, cilioretinal arteries, and vortex veins. Although postmortem injection cast preparations gave us useful information on the morphology of the choroidal vascular bed; in vivo studies showed that they misled us for centuries about the in vivo situation. According to the postmortem cast studies, the uveal vascular bed has no segmental distribution, the uveal vessels anastomose freely with one another, there are inter-arterial and arteriovenous anastomoses in the choroid, and the choriocapillaris form a freely communicating and an uninterrupted vascular bed in the entire choroid.


Assuntos
Corioide , Úvea , Humanos , Corioide/irrigação sanguínea , Capilares , Vasos Retinianos , Microcirculação
5.
Eye (Lond) ; 37(13): 2617-2648, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37185956

RESUMO

From studies on postmortem anatomical descriptions of the uveal vascular bed, it was generally concluded that occlusion of PCA or its branches should not produce an ischemic lesion. However, in vivo studies have recorded that the PCAs and their branches, right down to the terminal choroidal arterioles, and the choriocapillaris, have a segmental distribution in the choroid, and that PCAs and choroidal arteries function as end-arteries. This explains the basis of the occurrence of isolated inflammatory, ischemic, metastatic, and degenerative choroidal lesions, which are usually localized. Thus, in vivo studies have completely revolutionized our concept of the uveal vascular bed in disease.


Assuntos
Corioide , Úvea , Humanos , Corioide/patologia , Isquemia , Arteríolas
6.
Graefes Arch Clin Exp Ophthalmol ; 261(8): 2383-2394, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36933009

RESUMO

PURPOSE: To investigate the ultrasonographic features in patients with primary uveal mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: Medical records of 12 patients (13 eyes) diagnosed with primary uveal MALT lymphoma between September 2014 and September 2021 were retrospectively reviewed. Ultrasonography, B-scan ultrasonography, color Doppler flow imaging, and ultrasound biomicroscopy findings were retrieved from the medical records. RESULTS: Mean age of the included patients was 59.4 ± 8.6 years. Typical ultrasonographic features of the choroidal infiltrates were flat, diffuse, and thickened, with low and homogenous internal reflectivity and with rich arterial blood flow from posterior ciliary arterioles. The mean thickness of the choroidal infiltrates was 1.34 ± 0.68 mm (n = 13). Most of the affected eyes had posterior episcleral extensions, with a mean thickness of 1.66 ± 1.21 mm (n = 12). Typical crescent-like posterior episcleral extensions were detected in nine eyes (69.2%). In six eyes, the blood flow from the choroidal infiltrates communicated with the episcleral extensions. In the ciliary body, the mean thickness of the infiltrates was 1.08 ± 0.43 mm (n = 9), and seven eyes (77.8%) had 360° ring-like infiltrations. The initial best-corrected visual acuity (BCVA) was significantly correlated with the final BCVA after treatment (p < 0.001). CONCLUSION: Multipurpose ultrasonographic imaging revealed the unique characteristics of the primary uveal MALT lymphoma and is helpful in the diagnosis of this rare disease.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Úvea/patologia , Corpo Ciliar/patologia , Ultrassonografia
7.
Surv Ophthalmol ; 68(4): 669-677, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36878360

RESUMO

Uveitis is a disease complex characterized by intraocular inflammation of the uvea that is an important cause of blindness and social morbidity. With the dawn of artificial intelligence (AI) and machine learning integration in health care, their application in uveitis creates an avenue to improve screening and diagnosis. Our review identified the use of artificial intelligence in studies of uveitis and classified them as diagnosis support, finding detection, screening, and standardization of uveitis nomenclature. The overall performance of models is poor, with limited datasets and a lack of validation studies and publicly available data and codes. We conclude that AI holds great promise to assist with the diagnosis and detection of ocular findings of uveitis, but further studies and large representative datasets are needed to guarantee generalizability and fairness.


Assuntos
Inteligência Artificial , Uveíte , Humanos , Aprendizado de Máquina , Uveíte/diagnóstico , Atenção à Saúde , Úvea
8.
Am J Ophthalmol ; 241: 1-8, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35358486

RESUMO

PURPOSE: To determine the visual outcomes and effectiveness of glaucoma surgeries in congenital ectropion uvea. DESIGN: Retrospective interventional case series. METHODS: Surgeries and examination findings were collected on 11 eyes of 8 patients with congenital ectropion uvea at 2 academic sites from 2001 to 2021. Visual outcomes, surgical success (intraocular pressure [IOP]: 5-20 mm Hg, no additional IOP-lowering surgery, no visually devastating complications), and survival rates of glaucoma surgeries were assessed. RESULTS: Glaucoma in bilateral congenital ectropion uvea was diagnosed at an earlier age (0.02 ± 0.01 years) than unilateral disease (8.9 ± 5.3 years, P = .002). All eyes required glaucoma surgery with 91% requiring multiple surgeries (3.5 ± 2.1, median 3 surgeries per eye). Trabeculotomy (8 eyes) showed 13% success rate. Although none of the 4 eyes that underwent trabeculectomy with mitomycin C needed repeat trabeculectomy, glaucoma drainage device placement, or cycloablation, 75% required bleb revision surgery. Glaucoma drainage devices (7 eyes) had a 57% success rate with 3 eyes requiring subsequent cycloablation (2) or trabeculectomy (1). At the final follow-up (8.5 ± 6.6 years, median: 7.9 years), all eyes achieved IOP control, and IOP was lower compared with presentation (13.2 ± 2.6 mm Hg vs 32.9 ± 9.9 mm Hg, P = .002). Best-corrected logarithm of the minimum angle of resolution visual acuity at the final follow-up was 0.2 ± 0.2. CONCLUSIONS: Bilateral congenital ectropion uvea presents with glaucoma earlier than unilateral cases. The majority of eyes required multiple glaucoma surgeries. Angle surgery was less effective than trabeculectomy or glaucoma drainage devices. IOP control was obtained in all eyes and affected individuals had good visual outcomes.


Assuntos
Ectrópio , Glaucoma , Trabeculectomia , Ectrópio/cirurgia , Seguimentos , Glaucoma/complicações , Glaucoma/congênito , Glaucoma/cirurgia , Humanos , Recém-Nascido , Pressão Intraocular , Estudos Retrospectivos , Resultado do Tratamento , Úvea
9.
Vet Med Sci ; 8(3): 1036-1048, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35122675

RESUMO

OBJECTIVE: Gross, histopathological, and immunohistochemical characteristics of uveal melanocytic neoplasms in dogs and cats were investigated. SAMPLES: Thirty-two enucleated globes with uveal melanocytic neoplasms, 27 from dogs and 5 from cats, were examined. PROCEDURES: Morphological characteristics of uveal melanocytic neoplasms in dogs and cats were evaluated with anti-PNL2, anti-Melan-A, anti-Ki-67, anti-caspase-3, and anti-BAP1 immunomarkers. Statistical analysis was performed to compare canine melanocytomas and melanomas. RESULTS: The 32 uveal neoplasms were classified as melanocytomas (19/27 in dogs) or melanomas (8/27 in dogs, 5/5 in cats). Most tumours (84%) were located in the anterior uvea. Neoplastic cells were classified as epithelioid, spindle-shaped, mixed, or special type (balloon and signet ring cells). The percentage of cells with melanin, melanin concentration within cells, anisocytosis and anisokaryosis, mitotic count, lymphocytic inflammation, necrosis, vascular invasion, and glaucoma were also characterized. Anisocytosis, percentage of neoplastic cells with melanin, mitotic count, and indices (proliferation and apoptotic) varied significantly between canine uveal melanomas and melanocytomas; in general, melanomas had greater cell variability, were less pigmented, and had a higher mitotic count. The melanocytic origin of the neoplasms was confirmed by positive anti-PNL2 immunolabelling (29/32) and positive anti-Melan-A immunolabelling (3/32). In canine uveal melanomas, anisocytosis and anisokaryosis correlated with less pigmentation and minimal pigmentation correlated with a high percentage of immunolabelling for caspase-3. CONCLUSIONS: Uveal melanocytomas were more common in dogs, and uveal melanomas were more frequent in cats. Anisocytosis, percentage of neoplastic cells with melanin, and mitotic count are important histologic characteristics of malignancy to evaluate in uveal melanocytic neoplasms. The proliferation and apoptotic indices are relevant when comparing malignant tumours with benign tumours.


Assuntos
Doenças do Gato , Doenças do Cão , Melanoma , Animais , Doenças do Gato/patologia , Gatos , Doenças do Cão/patologia , Cães , Melaninas , Melanoma/veterinária , Úvea/patologia
10.
Exp Eye Res ; 216: 108943, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35074346

RESUMO

Fibroblast-stimulating lipopeptide (FSL-1) can activate Toll-like receptor 2 and 6 (TLR2/6), which recognize relevant molecules from gram-positive pathogens, fungus, and mycoplasma, and elevates the expression of CXCL1 and CXCL2, neutrophil chemoattractants, in certain types of cells. This effect has not previously been reported in the uveal melanocytes (UM). This study was designed to test the hypothesis that FSL-1 can induce the expression and secretion of CXCL1 and CXCL2 via activation of TLR2/6 in cultured human UM and producing an acute non-infectious uveitis reaction in the mouse. Flow cytometry and fluorescent immunostaining were used to measure the effect of FSL-1 on the expression of TLR2/6 in UM. Real time PCR and ELISA analysis were used to assess the ability of FSL-1 to elevate CXCL1/CXCL2 levels in cell lysates and conditioned media of UM, respectively. Flow cytometry measured phosphorylated MAPK and activated NF-κB signals in UM, with and without FSL-1 treatment. ELISA analysis tested the impact of various signal inhibitors (NF-κB, p38 MAPK, JNK1/2 and ERK1/2) and TLR2/6 antagonists on FSL-1-induced CXCL1/CXCL2 levels in cultured UM. The effects of neutralizing antibodies to TLR2 on FSL-1-induced mouse uveitis were tested in an experimental animal model. FSL-1 induced the expression of TLR2/6 proteins in cultured UM. FSL-1 significantly elevated the CXCL1 and CXCL2 proteins and mRNA levels in cultured UM time- and dose-dependently. FSL-1 mainly activated NF-κB, JNK, and expression of TLR2. FSL-1-induced expression of CXCL1 and CXCL2 was blocked by NF-κB, JNK, ERK inhibitors and TLR2 antagonists. Intravitreal injection of FSL-1 induced acute non-infectious mouse uveitis, which was significantly reduced in severity by a TLR2 antagonist. These results suggest that UM may play a role in the immune reaction, which targets invading pathogens, especially gram-positive bacteria. On the other hand, an excessive reaction to molecules from gram-positive bacteria may promote an inflammatory state of non-infectious uveitis.


Assuntos
Quimiocina CXCL1/metabolismo , Quimiocina CXCL2/metabolismo , Diglicerídeos/farmacologia , Melanócitos/efeitos dos fármacos , Oligopeptídeos/farmacologia , Receptor 2 Toll-Like/agonistas , Receptor 6 Toll-Like/agonistas , Úvea/citologia , Animais , Anticorpos Neutralizantes/farmacologia , Células Cultivadas , Quimiocina CXCL1/genética , Quimiocina CXCL2/genética , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Injeções Intravítreas , Melanócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fosforilação , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Uveíte/induzido quimicamente , Uveíte/metabolismo
11.
Ophthalmic Plast Reconstr Surg ; 38(1): e19-e23, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34570046

RESUMO

We present an unusual case of a patient who acquired a pansinusitis and orbital cellulitis with necrotizing features, subsequently developing scleritis, keratitis, and anterior uveitis. To date, there are no reported cases of the simultaneous involvement of these ocular structures from a pansinusitis. Our patient was urgently taken to the operating room for drainage of the abscesses within his sinuses and the orbit. Intraoperative cultures were positive for Parvimonas micra, an odontogenic anaerobic bacteria. He was additionally found to have a central retinal artery occlusion. He was treated with systemic and topical antibiotics as well as topical dilute hypochlorous acid. The mechanisms of virulence of P. micra, including its synergistic relationship with other bacteria, ability to bind plasminogen, and its expression of proteases, contributed to this diffuse infection.


Assuntos
Panoftalmite , Córnea , Firmicutes , Humanos , Masculino , Órbita , Retina , Esclera , Úvea
12.
Surv Ophthalmol ; 67(3): 659-674, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34656556

RESUMO

The human eye has a unique immune architecture and behavior. While the conjunctiva is known to have a well-defined lymphatic drainage system, the cornea, sclera, and uveal tissues were historically considered "alymphatic" and thought to be immune privileged. The very fact that the aqueous outflow channels carry a clear fluid (aqueous humor) along the outflow pathway makes it hard to ignore its lymphatic-like characteristics. The development of novel lymphatic lineage markers and expression of these markers in aqueous outflow channels and improved imaging capabilities has sparked a renewed interest in the study of ocular lymphatics. Ophthalmic lymphatic research has had a directional shift over the last decade, offering an exciting new physiological platform that needs further in-depth understanding. The evidence of a presence of distinct lymphatic channels in the human ciliary body is gaining significant traction. The uveolymphatic pathway is an alternative new route for aqueous outflow and adds a new dimension to pathophysiology and management of glaucoma. Developing novel animal models, markers, and non-invasive imaging tools to delineate the core anatomical structure and physiological functions may help pave some crucial pathways to understand disease pathophysiology and help develop novel targeted therapeutic approaches for glaucoma.


Assuntos
Glaucoma , Vasos Linfáticos , Animais , Humor Aquoso/metabolismo , Humanos , Pressão Intraocular , Esclera , Malha Trabecular , Úvea
13.
BMC Cancer ; 21(1): 1068, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587931

RESUMO

BACKGROUND: Uveal melanoma (UVM) is the leading cause of eye-related mortality worldwide. This study aimed to explore the expression and prognostic value of matrix metalloproteinases (MMPs) in UVM. METHODS: Gene expression levels were obtained from the Gene Expression Omnibus (GEO) and Oncomine databases. Functional and pathway enrichment analyses were performed using the Metascape database. GeneMANIA was then applied to construct a protein-protein interaction network and identify the hub genes. Moreover, overall survival (OS) and disease-free survival (DFS) analysis for the hub genes was performed using the UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) online tool. Furthermore, TRRUST was used to predict the targets of the MMPs. RESULTS: Our results revealed that the transcriptional levels of MMP1, MMP9, MMP10, MMP11, MMP13, MMP14, and MMP17 were upregulated in UVM tissues compared to normal tissues. A protein-protein interaction (PPI) network was constructed and the top 50 hub genes were identified. The functions of MMPs and their neighboring proteins are mainly associated with ECM-receptor interaction, proteoglycans in cancer, the IL-17 signaling pathway, and microRNAs in cancer. Among the MMPs, MMP1/2/9/11/14/15/16/17/24 played significant roles in the progression of UVM from stage 3 to stage 4. We also found that the expression of MMP1, MMP2, MMP9, and MMP16 positively correlated with OS and DFS in patients with UVM. Additionally, 18 transcription factors associated with nine MMPs were identified. CONCLUSIONS: The results of this study may provide potential biomarkers and targets for UVM. However, further studies are required to confirm these results.


Assuntos
Biomarcadores Tumorais/metabolismo , Colagenases/metabolismo , Melanoma/enzimologia , Mapas de Interação de Proteínas/genética , Neoplasias Uveais/enzimologia , Biomarcadores Tumorais/genética , Colagenases/genética , Bases de Dados Genéticas , Progressão da Doença , Intervalo Livre de Doença , Perfilação da Expressão Gênica/métodos , Humanos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Melanoma/genética , Melanoma/mortalidade , Melanoma/patologia , Prognóstico , Fatores de Transcrição/metabolismo , Regulação para Cima , Úvea/enzimologia , Neoplasias Uveais/genética , Neoplasias Uveais/mortalidade , Neoplasias Uveais/patologia
14.
Invest Ophthalmol Vis Sci ; 62(10): 10, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34379096

RESUMO

Purpose: In spite of clear differences in tissue function and significance to ocular disease, little is known about how immune responses differ between the retina and uveal tract. To this end we compared the effects of acute systemic inflammation on myeloid cells within the mouse retina, iris-ciliary body, and choroid. Methods: Systemic inflammation was induced in Cx3cr1gfp/gfp and CD11c-eYFP Crb1wt/wtmice by intraperitoneal lipopolysaccharide (LPS). In vivo fundus imaging was performed at two, 24, and 48 hours after LPS, and ocular tissue wholemounts were immunostained and studied by confocal microscopy. Flow cytometry was used to investigate the expression of activation markers (MHC class II, CD80, CD86) on myeloid cell populations at 24 hours. For functional studies, retinal microglia were isolated from LPS-exposed mice and cocultured with naïve OT-II CD4+ T-cells and ovalbumin peptide. T-cell proliferation was measured by flow cytometry and cytokine assays. Results: Systemic LPS altered the density and morphology of retinal microglia; however, retinal microglia did not upregulate antigen presentation markers and failed to stimulate naïve CD4+ T-cell proliferation in vitro. In contrast, uveal tract myeloid cells displayed a phenotype consistent with late-activated antigen-presenting cells at 24 hours. Systemic LPS induced remodeling of myeloid populations within the uveal tract, particularly in the choroid, where dendritic cells were partially displaced by macrophages at 24 hours. Conclusions: The disparate myeloid cell responses in the retina and uveal tract after systemic LPS highlight differential regulation of innate immunity within these tissue environments, observations that underpin and advance our understanding of ocular immune privilege.


Assuntos
Células Dendríticas/patologia , Inflamação/patologia , Macrófagos/patologia , Células Mieloides/patologia , Retina/patologia , Úvea/patologia , Animais , Células Dendríticas/imunologia , Modelos Animais de Doenças , Citometria de Fluxo , Inflamação/imunologia , Inflamação/metabolismo , Macrófagos/imunologia , Camundongos Endogâmicos BALB C , Microscopia Confocal , Células Mieloides/imunologia , Retina/imunologia , Úvea/imunologia
15.
Front Immunol ; 12: 623725, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995347

RESUMO

The profound impact that vision loss has on human activities and quality of life necessitates understanding the etiology of potentially blinding diseases and their clinical management. The unique anatomic features of the eye and its sequestration from peripheral immune system also provides a framework for studying other diseases in immune privileged sites and validating basic immunological principles. Thus, early studies of intraocular inflammatory diseases (uveitis) were at the forefront of research on organ transplantation. These studies laid the groundwork for foundational discoveries on how immune system distinguishes self from non-self and established current concepts of acquired immune tolerance and autoimmunity. Our charge in this review is to examine how advances in molecular cell biology and immunology over the past 3 decades have contributed to the understanding of mechanisms that underlie immunopathogenesis of uveitis. Particular emphasis is on how advances in biotechnology have been leveraged in developing biologics and cell-based immunotherapies for uveitis and other neuroinflammatory diseases.


Assuntos
Anti-Inflamatórios/uso terapêutico , Autoimunidade/efeitos dos fármacos , Produtos Biológicos/uso terapêutico , Tolerância Imunológica/efeitos dos fármacos , Imunoterapia , Úvea/efeitos dos fármacos , Uveíte/terapia , Animais , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Terapia de Alvo Molecular , Transdução de Sinais , Úvea/imunologia , Úvea/metabolismo , Uveíte/imunologia , Uveíte/metabolismo
16.
Vet Ophthalmol ; 24(4): 354-360, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33977630

RESUMO

OBJECTIVE: To demonstrate the existence of lymphatics in the canine anterior uvea using lymphatic-specific markers Lyve-1, Prox-1, and podoplanin, the endothelial cell marker CD31, and basement membrane matrix marker collagen IV. DESIGN: Prospective Study. ANIMALS: Eight normal globes from animals euthanized for unrelated health problems. PROCEDURES: Sagittally cut serial sections of six normal canine eyes were immunofluorescence double-stained with Lyve-1 and CD31 and single-stained with colorimetric Prox-1 and collagen IV. Three serial sections from 2 additional eyes were cut in the coronal plane at the level of the ciliary body and immunofluorescence double-stained with Lyve-1 and CD31 to map lymphatic channel distribution. Lymphatics from normal canine lymph nodes were used for validation of podoplanin. RESULTS: Four of 6 of the sagitally sectioned eyes had Lyve-1-positive lymphatic-like structures that were distinct from CD31-positive blood vessels in the iris base and ciliary body. Both of the coronally sectioned globes had Lyve-1-positive lymphatic-like structures in the ciliary body. The location of these structures was evaluated and found to be diffusely present circumferentially around the ciliary body. CONCLUSION AND CLINICAL RELEVANCE: These results support the existence of lymphatic channels in the anterior uveal tract of the canine eye. This could indicate the presence of a novel uveolymphatic outflow pathway, which may play a role in aqueous humor outflow. Future studies are needed to confirm the existence and elucidate the role of this proposed uveolymphatic outflow pathway and potentially develop novel treatment options for managing glaucoma.


Assuntos
Cães/anatomia & histologia , Vasos Linfáticos/anatomia & histologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Úvea/anatomia & histologia , Proteínas de Transporte Vesicular/metabolismo , Animais , Antígenos de Diferenciação/metabolismo , Corpo Ciliar/anatomia & histologia , Imunofluorescência/veterinária , Glicoproteínas de Membrana/metabolismo , Estudos Prospectivos
17.
Australas J Dermatol ; 62(3): 386-389, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33974277

RESUMO

Bilateral diffuse uveal melanocytic proliferation (B-DUMP) is a rare paraneoplastic syndrome typically presenting with bilateral visual loss. B-DUMP is associated with extraocular systemic malignancies with the most common being lung cancer in males and uro-gynaecological cancer in females (mainly ovarian cancer). Cutaneous and/or mucosal involvement in patients with B-DUMP has been reported but it is not well characterised. Herein, we present a female in her 70s with diagnosis of stage IV vaginal clear-cell carcinoma and metastatic melanoma of unknown primary that developed progressive bilateral loss of visual acuity compatible with 'B-DUMP'. Simultaneously, she developed multifocal bilateral bluish-greyish patches on the skin that were shown to have a proliferation of dermal melanocytes. We propose that the clinical and histopathologic cutaneous findings seen in patients with B-DUMP be termed 'diffuse integumentary melanocytic proliferation (DIMP)'.


Assuntos
Adenocarcinoma de Células Claras/patologia , Síndromes Paraneoplásicas Oculares/patologia , Úvea/patologia , Neoplasias Vaginais/patologia , Adenocarcinoma de Células Claras/complicações , Idoso , Feminino , Humanos , Síndromes Paraneoplásicas Oculares/complicações , Neoplasias Vaginais/complicações
18.
Curr Eye Res ; 46(11): 1681-1694, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33979551

RESUMO

Purpose: Lipopolysaccharide (LPS) can activate Toll-like receptor 4 (TLR4) and increase the expression of CXCL1 and CXCL2, the potent neutrophils chemoattractants, in various cell types. These effects have not been previously reported in the uveal melanocytes. This study was designed to investigate the effects of LPS on the activation of TLR4 and expression of CXCL1/CXCL2 in cultured human uveal melanocytes and the relevant signal pathways.Methods: Effects of LPS on the expression of TLR4 were tested using real-time PCR, flow cytometry and fluorescence immunostaining. Effects of LPS-induced expression/secretion of CXCL1/CXCL2 were studied using real-time PCR in cell lysates and ELISA in conditioned media of cultured uveal melanocytes. Activated NF-κB and phosphorylated MAPK signals were tested in cells with and without LPS treatment using flow cytometry. Effects of various signal inhibitors on p38, ERK1/2, JNK1/2 and NF-κB on the secretion of CXCL1/CXCL2 were tested by ELISA. The effects of neutralized antibodies of CXCL1/CXCL2 on the severity of LPS-induced uveitis were tested in a mouse model.Results: LPS stimulation increased the expression of TLR4 mRNA and protein in culture uveal melanocytes. Constitutive secretion of CXCL1/CXCL2 was detected in uveal melanocytes and was significantly increased dose- and time-dependently by LPS stimulation. LPS mainly increased the activated NF-κB and phosphorylated JNK1/2. LPS-induced expression of CXCL1/CXCL2 was blocked by NF-κB and JNK1/2 inhibitors. The severity of LPS-induced uveitis was significantly inhibited by neutralizing antibody to CXCL1/CXCL2Conclusions: This is the first report on the LPS-induced expression of CXCL1 and CXCL2 by uveal melanocytes via the activation of TLR4. These results suggest that uveal melanocytes may play a role in the immune reaction that eliminates the invading pathogens. Conversely, an excessive LPS-induced inflammatory reaction may also lead to the development of inflammatory ocular disorders, such as non-infectious uveitis.


Assuntos
Quimiocina CXCL1/metabolismo , Lipopolissacarídeos/farmacologia , Melanócitos/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Úvea/citologia , Animais , Anticorpos Neutralizantes/farmacologia , Células Cultivadas , Quimiocina CXCL1/imunologia , Quimiocina CXCL2/imunologia , Quimiocina CXCL2/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Melanócitos/metabolismo , Melanoma/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Uveais/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Ocul Immunol Inflamm ; 29(4): 700-704, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-33856952

RESUMO

Purpose: To report bilateral anterior uveitis and corneal punctate epitheliopathy in children with multisystem inflammatory syndrome (MIS-C) secondary to coronavirus disease (COVID-19).Participants and methods: Five patients who were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies and diagnosed with MIS-C were evaluated. Ophthalmologic examinations were performed in order to reveal ocular findings in MIS-C disease.Results: Slit lamp examinations showed bilateral non-granulomatous acute anterior uveitis in all patients and severe corneal punctuate epitheliopathy in three of the patients. These ocular findings mostly disappeared with treatment in about one week.Conclusion: Bilateral non-granulomatous acute anterior uveitis and dry eye can be detected in patients diagnosed with MIS-C secondary to COVID-19. Even if generally, COVID-19 is not a life threatening disease in children by itself, inflammatory ocular manifestations can be detected in MIS-C secondary to COVID-19.


Assuntos
Anticorpos Antivirais/análise , COVID-19/complicações , Córnea/patologia , Doenças da Córnea/etiologia , Infecções Oculares Virais/etiologia , SARS-CoV-2/imunologia , Síndrome de Resposta Inflamatória Sistêmica/complicações , Uveíte Anterior/etiologia , Adolescente , COVID-19/diagnóstico , COVID-19/virologia , Criança , Córnea/virologia , Doenças da Córnea/diagnóstico , Doenças da Córnea/virologia , Infecções Oculares Virais/diagnóstico , Infecções Oculares Virais/virologia , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Microscopia com Lâmpada de Fenda , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/virologia , Úvea/patologia , Úvea/virologia , Uveíte Anterior/diagnóstico , Uveíte Anterior/virologia
20.
Ocul Immunol Inflamm ; 29(4): 681-683, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-33826479

RESUMO

Purpose: To present a a case study that aims to investigate the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the ocular tissue samples of a patient previously infected with COVID-19 and determine its transmissibility.Study Design: Case ReportResults: In this case study, SARS-CoV-2 was not detected in the vitreous and uveal tissue samples by RT-PCR for detection of three gene targets in a patient with a past COVID-19 infection 15 days prior to presention with a globe rupture.Conclusions: Our findings suggest that patients with long-term existence of SARS-CoV-2 at low detectable levels may not have active intraocular viral shedding. This is of particular importance as ophthalmic surgical procedures may potentiate virus spread from patients infected with SARS-CoV-2.


Assuntos
COVID-19/virologia , Infecções Oculares Virais/diagnóstico , RNA Viral/análise , SARS-CoV-2/genética , Úvea/virologia , Corpo Vítreo/virologia , Adulto , COVID-19/complicações , COVID-19/diagnóstico , Infecções Oculares Virais/etiologia , Infecções Oculares Virais/virologia , Feminino , Humanos , Manejo de Espécimes , Eliminação de Partículas Virais
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