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1.
Ocul Surf ; 24: 74-82, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35231640

RESUMO

INTRODUCTION: Ocular surface masqueraders encompass any ocular surface lesion masquerading as another ocular surface lesion. High resolution optical coherence tomography (HR-OCT) has emerged as an adjunctive tool to clinical acumen. This study's purpose is to evaluate the utility of HR-OCT images in guiding the diagnosis and management of those lesions. MATERIAL AND METHODS: 22 individuals with a clinically ambiguous ocular surface lesion with slit lamp photographs (SLP), HR-OCT images, and histopathological examination were included in the study. The presumptive clinical diagnosis based on SLP was compared to the diagnosis suggested by HR-OCT findings and to definitive diagnosis by histopathology. The main outcome of this study was the frequency in which HR-OCT findings guided the clinician to the correct diagnosis. RESULTS: 7 lesions were epithelial, 3 had an epithelial and a subepithelial component, and 12 were subepithelial. HR-OCT was most effective in discerning lesion location, successfully identifying the location in 100% of cases. Classic HR-OCT findings were detected in 68.2% of cases while suggestive features were detected in 31.8% of cases. The epithelial lesions' mean epithelial thickness was 265.4 ± 140.6 µm, the subepithelial lesions' mean was 58.0 ± 25.0 µm, and the combined lesions' mean was 140.0 ± 70.0 µm. The epithelium was significantly thicker in epithelial lesions compared to subepithelial and combined lesions. By ROC analysis we identified that using a cut off of 156 µm, the sensitivity was 86% and the specificity was 93%. DISCUSSION: HR-OCT can be a valuable diagnostic tool, assisting in the differentiation of ambiguous ocular surface pathologies by providing a cross-sectional, morphological image of the lesion.


Assuntos
Neoplasias Oculares , Tomografia de Coerência Óptica , Estudos Transversais , Olho/patologia , Neoplasias Oculares/diagnóstico , Humanos , Tomografia de Coerência Óptica/métodos
2.
Exp Cell Res ; 414(2): 113086, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35283101

RESUMO

In 2015, Brazil reported an outbreak identified as Zika virus (ZIKV) infection associated with congenital abnormalities. To date, a total of 86 countries and territories have described evidence of Zika infection and recently the appearance of the African ZIKV lineage in Brazil highlights the risk of a new epidemic. The spectrum of ZIKV infection-induced alterations at both cellular and molecular levels is not completely elucidated. Here, we present for the first time the gene expression responses associated with prenatal ZIKV infection from ocular cells. We applied a recently developed non-invasive method (impression cytology) which use eye cells as a model for ZIKV studies. The ocular profiling revealed significant differences between exposed and control groups, as well as a different pattern in ocular transcripts from Congenital Zika Syndrome (CZS) compared to ZIKV-exposed but asymptomatic infants. Our data showed pathways related to mismatch repair, cancer, and PI3K/AKT/mTOR signaling and genes probably causative or protective in the modulation of ZIKV infection. Ocular cells revealed the effects of ZIKV infection on primordial neuronal cell genes, evidenced by changes in genes associated with embryonic cells. The changes in gene expression support an association with the gestational period of the infection and provide evidence for the resulting clinical and ophthalmological pathologies. Additionally, the findings of cell death- and cancer-associated deregulated genes raise concerns about the early onset of other potential pathologies including the need for tumor surveillance. Our results thus provide direct evidence that infants exposed prenatally to the Zika virus, not only with CZS but also without clinical signs (asymptomatic) express cellular and molecular changes with potential clinical implications.


Assuntos
Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Olho/patologia , Feminino , Humanos , Lactente , Fosfatidilinositol 3-Quinases , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/genética , Zika virus/genética , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/genética
3.
J Control Release ; 344: 261-271, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35278493

RESUMO

In vivo self-assembly of small molecules offers an excellent opportunity for targeted and long-term accumulation of a therapeutic agent at the lesion site. Here we demonstrate the strategy of enzyme-instructed self-assembly (EISA) by designing a phosphorylated peptide-drug (IBF-HYD-GFFpY) precursor through the ester bond to release active drugs at the target site. Meanwhile, the in vivo assembly can be achieved by the catalysis of alkaline phosphatase (ALP) in the tear fluid for ocular drug delivery efficiently. The in vitro enzymatic experiments indicate that the dephosphorylation of IBF-HYD-GFFpY occurs firstly with the yield of IBF-HYD-GFFY which subsequently self-assembles into the supramolecular hydrogel to afford sustained drug release over 96 h. In the treatment of lipopolysaccharide (LPS)-activated Raw 264.7 macrophages, IBF-HYD-GFFpY exerts the more potent anti-inflammatory efficacy than that of free ibuprofen (IBF) at the concentration of 200 µM. Moreover, the aqueous solution of IBF-HYD-GFFpY via topical instillation hardly causes ocular irritation, and displays longer precorneal retention compared to the conventional eye drop formulation. In addition, in the in vivo study, a rabbit model of endotoxin-induced uveitis (EIU) evidences the comparable therapeutic efficacy of IBF-HYD-GFFpY eye drops with that of clinically used 0.1 wt% diclofenac (DIC) sodium eye drops by the reduction of macrophage and leukocyte influx. This work, in situ EISA in the tear microenvironment directing in vivo self-assembly of small molecules, may guide a powerful approach for developing enzymatic self-assembled molecules as an efficient delivery system of ocular drugs.


Assuntos
Sistemas de Liberação de Medicamentos , Uveíte , Animais , Olho/patologia , Hidrogéis/química , Peptídeos/química , Coelhos , Uveíte/patologia
4.
Int J Mol Sci ; 23(2)2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-35054783

RESUMO

Of increasing prevalence, diabetes is characterised by elevated blood glucose and chronic inflammation that precedes the onset of multiple secondary complications, including those of the kidney and the eye. As the leading cause of end stage renal disease and blindness in the working population, more than ever is there a demand to develop clinical interventions which can both delay and prevent disease progression. Connexins are membrane bound proteins that can form pores (hemichannels) in the cell membrane. Gated by cellular stress and injury, they open under pathophysiological conditions and in doing so release 'danger signals' including adenosine triphosphate into the extracellular environment. Linked to sterile inflammation via activation of the nod-like receptor protein 3 inflammasome, targeting aberrant hemichannel activity and the release of these danger signals has met with favourable outcomes in multiple models of disease, including secondary complications of diabetes. In this review, we provide a comprehensive update on those studies which document a role for aberrant connexin hemichannel activity in the pathogenesis of both diabetic eye and kidney disease, ahead of evaluating the efficacy of blocking connexin-43 specific hemichannels in these target tissues on tissue health and function.


Assuntos
Conexina 43/metabolismo , Complicações do Diabetes/terapia , Olho/patologia , Inflamação/metabolismo , Inflamação/terapia , Rim/patologia , Animais , Humanos , Microvasos/patologia
5.
PLoS One ; 17(1): e0263352, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35100315

RESUMO

PURPOSE: To examine the prevalence and risk factors of intraocular pathologies after mature cataract surgery. METHODS: The medical records of 115 patients (115 eyes) diagnosed with brunescent or white cataracts, who underwent surgery at a single primary center between January 2018 and August 2021 were retrospectively reviewed. Dense cataracts precluded preoperative fundus examination in all eyes; however, patients with fundus examination results within 3 months after cataract surgery were included. Logistic regression analyses were performed to identify factors associated with intraocular pathologies. RESULTS: Intraocular pathologies were observed in 37 eyes (32.2%) 11.8 ± 13.9 days postoperatively. The most common abnormalities were drusen (6.1%), myopic degeneration (5.2%) and diabetic retinopathy (4.3%). Intraocular pathology in the fellow eye was associated with posterior segment pathology in mature cataract eyes (odds ratio, 47.72; P < 0.001). CONCLUSIONS: The prevalence of each intraocular pathology found after mature cataract surgery was unremarkable. This study provides clinically useful evidence for clinicians to explain the risk of posterior segment pathology in patients with mature cataracts.


Assuntos
Extração de Catarata/efeitos adversos , Catarata/patologia , Olho/patologia , Complicações Pós-Operatórias/etiologia , Idoso , Catarata/diagnóstico por imagem , Olho/diagnóstico por imagem , Análise Fatorial , Feminino , Fundo de Olho , Humanos , Modelos Logísticos , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Tomografia de Coerência Óptica
6.
Mucosal Immunol ; 15(2): 351-361, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34775490

RESUMO

Autoimmune uveitis is a sight-threatening disease induced by pathogenic T cells that recognize retinal antigens; it is observed in disorders including Vogt-Koyanagi-Harada disease (VKH). The roles of specific T cell subsets and their therapeutic potential against autoimmune uveitis are not fully understood. Here we conducted multi-parametric single-cell protein quantification which shows that the frequency of CD161highTRAV1-2+ mucosal-associated invariant T (MAIT) cells that recognize vitamin B2 metabolite-based antigens is decreased in relapsing VKH patients compared to individuals without active ocular inflammation. An experimental autoimmune uveitis (EAU) mouse model revealed that genetic depletion of MAIT cells reduced the expression of interleukin (Il) 22 and exacerbated retinal pathology. Reduced IL-22 levels were commonly observed in patients with relapsing VKH compared to individuals without active ocular inflammation. Both mouse and human MAIT cells produced IL-22 upon stimulation with their antigenic metabolite in vitro. An intravitreal administration of the antigenic metabolite into EAU mice induced retinal MAIT cell expansion and enhanced the expressions of Il22, as well as its downstream genes related to anti-inflammatory and neuroprotective effects, leading to an improvement in both retinal pathology and visual function. Taken together, we demonstrate that a metabolite-driven approach targeting MAIT cells has therapeutic potential against autoimmune uveitis.


Assuntos
Células T Invariantes Associadas à Mucosa , Uveíte , Síndrome Uveomeningoencefálica , Animais , Autoimunidade , Olho/patologia , Humanos , Camundongos , Células T Invariantes Associadas à Mucosa/metabolismo , Uveíte/metabolismo , Uveíte/patologia
7.
Mol Genet Metab ; 135(2): 143-153, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34417096

RESUMO

Maroteaux - Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is a lysosomal storage disease resulting from insufficient enzymatic activity for degradation of the specific glycosaminoglycans (GAG) chondroitin sulphate (CS) and dermatan sulphate (DS). Among the most pronounced MPS VI clinical manifestations caused by cellular accumulation of excess CS and DS are eye disorders, in particular those that affect the cornea. Ocular manifestations are not treated by the current standard of care, enzyme replacement therapy (ERT), leaving patients with a significant unmet need. Using in vitro and in vivo models, we previously demonstrated the potential of the ß-D-xyloside, odiparcil, as an oral GAG clearance therapy for MPS VI. Here, we characterized the eye phenotypes in MPS VI arylsulfatase B deficient mice (Arsb-) and studied the effects of odiparcil treatment in early and established disease models. Severe levels of opacification and GAG accumulation were detected in the eyes of MPS VI Arsb- mice. Histological examination of MPS VI Arsb- eyes showed an aggregate of corneal phenotypes, including reduction in the corneal epithelium thickness and number of epithelial cell layers, and morphological malformations in the stroma. In addition, colloidal iron staining showed specifically GAG accumulation in the cornea. Orally administered odiparcil markedly reduced GAG accumulation in the eyes of MPS VI Arsb- mice in both disease models and restored the corneal morphology (epithelial layers and stromal structure). In the early disease model of MPS VI, odiparcil partially reduced corneal opacity area, but did not affect opacity area in the established model. Analysis of GAG types accumulating in the MPS VI Arsb- eyes demonstrated major contribution of DS and CS, with some increase in heparan sulphate (HS) as well and all were reduced with odiparcil treatment. Taken together, we further reveal the potential of odiparcil to be an effective therapy for eye phenotypes associated with MPS VI disease.


Assuntos
Oftalmopatias/tratamento farmacológico , Glicosídeos , Mucopolissacaridose VI , N-Acetilgalactosamina-4-Sulfatase , Animais , Modelos Animais de Doenças , Olho/patologia , Oftalmopatias/genética , Glicosídeos/uso terapêutico , Humanos , Camundongos , Mucopolissacaridose VI/tratamento farmacológico , Mucopolissacaridose VI/genética , N-Acetilgalactosamina-4-Sulfatase/genética , Fenótipo
10.
Int J Mol Sci ; 22(22)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34830007

RESUMO

Primary Open-Angle Glaucoma (POAG) is a neurodegenerative disease, and its clinical outcomes lead to visual field constriction and blindness. POAG's etiology is very complex and its pathogenesis is mainly explained through both mechanical and vascular theories. The trabecular meshwork (TM), the most sensitive tissue of the eye anterior segment to oxidative stress (OS), is the main tissue involved in early-stage POAG, characterized by an increase in pressure. Preclinical assessments of neuroprotective drugs on animal models have not always shown correspondence with human clinical studies. In addition, intra-ocular pressure management after a glaucoma diagnosis does not always prevent blindness. Recently, we have been developing an innovative in vitro 3Dadvanced human trabecular cell model on a millifluidicplatform as a tool to improve glaucoma studies. Herein, we analyze the effects of prolonged increased pressure alone and, in association with OS, on such in vitro platform. Moreover, we verify whethersuch damaged TM triggers apoptosis on neuron-like cells. The preliminary results show that TM cells are less sensitive to pressure elevation than OS, and OS-damaging effects were worsened by the pressure increase. The stressed TM releases harmful signals, which increase apoptosis stimuli on neuron-like cells, suggesting its pivotal role in the glaucoma cascade.


Assuntos
Glaucoma de Ângulo Aberto/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Malha Trabecular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular , Olho/metabolismo , Olho/patologia , Glaucoma de Ângulo Aberto/genética , Glaucoma de Ângulo Aberto/metabolismo , Glaucoma de Ângulo Aberto/patologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Malha Trabecular/metabolismo , Malha Trabecular/patologia
11.
Cells ; 10(11)2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34831393

RESUMO

Uveitis is one of the main causes of blindness worldwide, and therapeutic alternatives are worthy of study. We investigated the effects of piperlongumine (PL) and/or annexin A1 (AnxA1) mimetic peptide Ac2-26 on endotoxin-induced uveitis (EIU). Rats were inoculated with lipopolysaccharide (LPS) and intraperitoneally treated with Ac2-26 (200 µg), PL (200 and 400 µg), or Ac2-26 + PL after 15 min. Then, 24 h after LPS inoculation, leukocytes in aqueous humor, mononuclear cells, AnxA1, formyl peptide receptor (fpr)1, fpr2, and cyclooxygenase (COX)-2 were evaluated in the ocular tissues, along with inflammatory mediators in the blood and macerated supernatant. Decreased leukocyte influx, levels of inflammatory mediators, and COX-2 expression confirmed the anti-inflammatory actions of the peptide and pointed to the protective effects of PL at higher dosage. However, when PL and Ac2-26 were administered in combination, the inflammatory potential was lost. AnxA1 expression was elevated among groups treated with PL or Ac2-26 + PL but reduced after treatment with Ac2-26. Fpr2 expression was increased only in untreated EIU and Ac2-26 groups. The interaction between Ac2-26 and PL negatively affected the anti-inflammatory action of Ac2-26 or PL. We emphasize that the anti-inflammatory effects of PL can be used as a therapeutic strategy to protect against uveitis.


Assuntos
Anexina A1/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Dioxolanos/uso terapêutico , Peptídeos/uso terapêutico , Uveíte/induzido quimicamente , Uveíte/tratamento farmacológico , Animais , Anexina A1/administração & dosagem , Anexina A1/farmacologia , Anti-Inflamatórios/farmacologia , Cílios/enzimologia , Cílios/patologia , Ciclo-Oxigenase 2/metabolismo , Dioxolanos/administração & dosagem , Dioxolanos/farmacologia , Endotoxinas , Olho/efeitos dos fármacos , Olho/patologia , Mediadores da Inflamação/metabolismo , Masculino , Modelos Biológicos , Monócitos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Peptídeos/administração & dosagem , Peptídeos/farmacologia , Ratos Wistar , Receptores de Lipoxinas/metabolismo , Uveíte/sangue , Uveíte/patologia
12.
Sci Rep ; 11(1): 21663, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737335

RESUMO

This study aimed to validate and evaluate deep learning (DL) models for screening of high myopia using spectral-domain optical coherence tomography (OCT). This retrospective cross-sectional study included 690 eyes in 492 patients with OCT images and axial length measurement. Eyes were divided into three groups based on axial length: a "normal group," a "high myopia group," and an "other retinal disease" group. The researchers trained and validated three DL models to classify the three groups based on horizontal and vertical OCT images of the 600 eyes. For evaluation, OCT images of 90 eyes were used. Diagnostic agreements of human doctors and DL models were analyzed. The area under the receiver operating characteristic curve of the three DL models was evaluated. Absolute agreement of retina specialists was 99.11% (range: 97.78-100%). Absolute agreement of the DL models with multiple-column model was 100.0% (ResNet 50), 90.0% (Inception V3), and 72.22% (VGG 16). Areas under the receiver operating characteristic curves of the DL models with multiple-column model were 0.99 (ResNet 50), 0.97 (Inception V3), and 0.86 (VGG 16). The DL model based on ResNet 50 showed comparable diagnostic performance with retinal specialists. The DL model using OCT images demonstrated reliable diagnostic performance to identify high myopia.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Miopia/diagnóstico , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Estudos Transversais , Aprendizado Profundo , Olho/patologia , Feminino , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Fibras Nervosas , Curva ROC , República da Coreia , Retina , Doenças Retinianas , Células Ganglionares da Retina , Estudos Retrospectivos , Campos Visuais
14.
Am J Trop Med Hyg ; 106(1): 62-65, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34695789

RESUMO

Infants ages < 6 months do not receive azithromycin as part of trachoma control and thus may serve as an infection reservoir in persistently endemic districts. The aim of this study was to determine the population-based Chlamydia trachomatis infection prevalence and infectious load among infants ages 1-12 months in persistently trachoma endemic districts in Amhara, Ethiopia. Across six districts, 475 infants were enumerated, and of these 464 (97.7%) were swabbed for infection testing. The C. trachomatis infection prevalence in the study area among infants was 0.2% (95% CI: 0.0-1.5). Among children ages 0-5 years positive for C. trachomatis, the median load was 31 elementary bodies (EB) (Inter quartile range: 7-244 EB), and the infection-positive infant had a load of 7,755 EB. While it is worth reconsidering azithromycin treatment recommendations for the potential mortality benefits, these results do not support lowering the treatment age for trachoma control.


Assuntos
Tracoma/epidemiologia , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Pré-Escolar , Chlamydia trachomatis/isolamento & purificação , Etiópia/epidemiologia , Olho/microbiologia , Olho/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/tratamento farmacológico , Doenças do Recém-Nascido/epidemiologia , Masculino , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/epidemiologia , Prevalência , Tracoma/tratamento farmacológico
15.
Genes (Basel) ; 12(9)2021 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-34573385

RESUMO

This study investigated the phenotypic spectrum of PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and early-onset cataract) syndrome caused by biallelic variants in the ABHD12 gene. A total of 15 patients from 12 different families were included, with a mean age of 36.7 years (standard deviation [SD] ± 11.0; range from 17.5 to 53.9) at the most recent examination. The presence and onset of neurological, audiological and ophthalmic symptoms were variable, with no evident order of symptom appearance. The mean best-corrected visual acuity was 1.1 logMAR (SD ± 0.9; range from 0.1 to 2.8; equivalent to 20/250 Snellen) and showed a trend of progressive decline. Different types of cataract were observed in 13 out of 15 patients (87%), which also included congenital forms of cataract. Fundus examination revealed macular involvement in all patients, ranging from alterations of the retinal pigment epithelium to macular atrophy. Intraretinal spicular hyperpigmentation was observed in 7 out of 15 patients (47%). From an ophthalmic perspective, clinical manifestations in patients with PHARC demonstrate variability with regard to their onset and severity. Given the variable nature of PHARC, an early multidisciplinary assessment is recommended to assess disease severity.


Assuntos
Ataxia , Catarata , Olho/fisiopatologia , Monoacilglicerol Lipases/genética , Polineuropatias , Retinite Pigmentosa , Adolescente , Adulto , Ataxia/genética , Ataxia/patologia , Ataxia/fisiopatologia , Bélgica , Catarata/genética , Catarata/patologia , Catarata/fisiopatologia , Estudos de Coortes , Olho/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Fenótipo , Polineuropatias/genética , Polineuropatias/patologia , Polineuropatias/fisiopatologia , Pseudofacia/genética , Pseudofacia/patologia , Pseudofacia/fisiopatologia , Retinite Pigmentosa/genética , Retinite Pigmentosa/patologia , Retinite Pigmentosa/fisiopatologia , Estudos Retrospectivos , Reino Unido , Acuidade Visual/fisiologia , Adulto Jovem
16.
Biomed Pharmacother ; 143: 112145, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34507119

RESUMO

Lupeol is a pentacyclic triterpene with known anti-inflammatory effects. However, its role in the treatment of noninfectious uveitis has not been explored. This work investigated anti-inflammatory activity of lupeol in ocular tissues with in vitro and in vivo models. First, we evaluated the effect of lupeol (100 µM) on inflammatory response induced by lipopolysaccharide (LPS) in retinal pigment epithelium cells (ARPE-19) by measuring levels of released interleukins (IL-6 and IL-8). Then, we investigated the anti-inflammatory action of intravitreal lupeol in a rodent model of panuveitis induced by Mycobacterium bovis Calmette-Guérin Bacillus (BCG). Rats were submitted to electroretinography and clinical analyses on days 3, 7, and 15 after uveitis induction. In addition, histopathological analysis, and indirect quantification of myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) in the posterior segment were performed. Treatment with lupeol (100 µM) significantly decreased IL-6 and IL-8 levels in comparison to untreated LPS-activated ARPE-19 cells. This reduction was similar to that detected in ARPE-19 cells treated with dexamethasone. The results of the in vivo assay demonstrated that intravitreal lupeol is able to modulate inflammation in the anterior and posterior segment of the rat eyes, indicating that it should be further investigated as a novel potential candidate for management of uveitis.


Assuntos
Anti-Inflamatórios/administração & dosagem , Olho/efeitos dos fármacos , Triterpenos Pentacíclicos/administração & dosagem , Uveíte/tratamento farmacológico , Acetilglucosaminidase/metabolismo , Animais , Vacina BCG , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Olho/metabolismo , Olho/patologia , Humanos , Mediadores da Inflamação/metabolismo , Injeções Intravítreas , Lipopolissacarídeos/toxicidade , Masculino , Peroxidase/metabolismo , Ratos Wistar , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Uveíte/induzido quimicamente , Uveíte/metabolismo , Uveíte/patologia
17.
Front Immunol ; 12: 701295, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394095

RESUMO

The current pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has already become a global threat to the human population. Infection with SARS-CoV-2 leads to a wide spectrum of clinical manifestations. Ocular abnormalities have been reported in association with COVID-19, but the nature of the impairments was not specified. Here, we report a case of a female patient diagnosed with glaucoma on re-hospitalization for ocular complications two months after being discharged from the hospital upon recovery from COVID-19. Meanwhile, the patient was found re-positive for SARS-CoV-2 in the upper respiratory tract. The infection was also diagnosed in the aqueous humor through immunostaining with antibodies against the N protein and S protein of SARS-CoV-2. Considering the eye is an immune-privileged site, we speculate that SARS-CoV-2 survived in the eye and resulted in the patient testing re-positive for SARS-CoV-2.


Assuntos
Humor Aquoso/virologia , COVID-19/patologia , Glaucoma/patologia , Reinfecção/patologia , Idoso , COVID-19/complicações , Olho/patologia , Olho/virologia , Feminino , Glaucoma/complicações , Humanos , SARS-CoV-2/isolamento & purificação
18.
Biomolecules ; 11(8)2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34439800

RESUMO

The eye is at the forefront of developing therapies for genetic diseases. With the FDA approval of the first gene-therapy drug for a form of congenital blindness, numerous studies have been initiated to develop gene therapies for other forms of eye diseases. These examinations have revealed new information about the benefits as well as restrictions to using drug-delivery routes to the different parts of the eye. In this article, we will discuss a brief history of gene therapy and its importance to the eye and ocular delivery landscape that is currently being investigated, and provide insights into their advantages and disadvantages. Efficient delivery routes and vehicle are crucial for an effective, safe, and longer-lasting therapy.


Assuntos
Oftalmopatias/terapia , Técnicas de Transferência de Genes , Terapia Genética/métodos , Vetores Genéticos/metabolismo , Animais , Efusões Coroides , DNA/genética , DNA/metabolismo , DNA/uso terapêutico , Olho/metabolismo , Olho/patologia , Oftalmopatias/genética , Oftalmopatias/metabolismo , Oftalmopatias/patologia , Vetores Genéticos/administração & dosagem , Vetores Genéticos/química , Humanos , Injeções Intravítreas , Lipossomos/química , Lipossomos/metabolismo , Lipossomos/uso terapêutico , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Peptídeos/uso terapêutico , Líquido Sub-Retiniano , Vírus/genética , Vírus/metabolismo , Corpo Vítreo
19.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445590

RESUMO

Leucine-rich a-2-glycoprotein 1 (LRG1) is a candidate therapeutic target for treating the neovascular form of age-related macular degeneration (nvAMD). In this study we examined the expression of LRG1 in eyes of nvAMD patients. Choroidal neovascular membranes (CNVMs) from patients who underwent submacular surgery for retinal pigment epithelium-choroid graft transplantation were collected from 5 nvAMD patients without any prior intravitreal anti-VEGF injection, and from six patients who received intravitreal anti-VEGF injections before surgery. As controls free of nvAMD, retina sections were obtained from the eyes resected from a patient with lacrimal sac tumor and from a patient with neuroblastoma. CNVMs were immunostained for CD34, LRG1, and α-smooth muscle actin (α-SMA). Aqueous humor samples were collected from 58 untreated-naïve nvAMD patients prior to the intravitreal injection of anti-VEGF and 51 age-matched cataract control patients, and LRG1 concentration was measured by ELISA. The level of LRG1 immunostaining is frequently high in both the endothelial cells of the blood vessels, and myofibroblasts in the surrounding tissue of CNVMs of treatment-naïve nvAMD patients. Furthermore, the average concentration of LRG1 was significantly higher in the aqueous humor of nvAMD patients than in controls. These observations provide a strong experimental basis and scientific rationale for the progression of a therapeutic anti-LRG1 monoclonal antibody into clinical trials with patients with nvAMD.


Assuntos
Neovascularização de Coroide/diagnóstico , Olho/patologia , Glicoproteínas/metabolismo , Degeneração Macular/diagnóstico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neovascularização de Coroide/metabolismo , Olho/metabolismo , Feminino , Humanos , Degeneração Macular/metabolismo , Masculino , Pessoa de Meia-Idade
20.
Genes (Basel) ; 12(7)2021 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-34356055

RESUMO

Bilateral convergent strabismus with exophthalmos (BCSE) is a malformation of the eyes and is recognized as a mild but progressive disorder that affects cattle in the first two years of life. This most likely inherited disorder is rarely described in cattle resembling autosomal dominantly inherited forms of human progressive external ophthalmoplegia (PEO). In German Braunvieh cattle, two linked genome regions were found that could be responsible for the development and/or progression of BCSE. The goal of this study was to phenotypically characterize BCSE in Holstein cattle from Germany and Switzerland as well as to identify associated genome regions by GWAS. The clinicopathological phenotype of 52 BCSE-affected Holstein cattle was in accordance with the phenotype described in German Braunvieh cattle, but in addition, signs of degeneration and cellular infiltration in the eye muscles were found. By using imputed sequence level genotype data, three genome-wide significant GWAS hits were revealed on different chromosomes that were not detected by initial GWAS based on high density SNP array data highlighting the usefulness of this approach for mapping studies. The associated genome regions include the ABCC4 gene as well as markers adjacent to the NCOR2 and DNAJC3 genes all illustrating possible functional candidate genes. Our results challenge a monogenic mode of inheritance and indicate a more complex inheritance of BCSE in Holstein cattle. Furthermore, in comparison to previous results from German Braunvieh cattle, it illustrates an obvious genetic heterogeneity causing BSCE in cattle. Subsequent whole genome sequencing (WGS)-based analyses might elucidate pathogenic variants in the future.


Assuntos
Esotropia/genética , Esotropia/veterinária , Exoftalmia/genética , Exoftalmia/veterinária , Estudo de Associação Genômica Ampla/veterinária , Genótipo , Animais , Bovinos/genética , Doenças dos Bovinos/genética , Cromossomos , Esotropia/patologia , Exoftalmia/patologia , Olho/patologia , Feminino , Genoma , Alemanha , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Doenças Raras/genética , Suíça
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