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1.
J Clin Med ; 13(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38337442

RESUMO

Patient expectations for cataract surgery are continuously increasing, and dry eye disease (DED) represents a major cause of patient dissatisfaction in eye surgery. The present opinion paper aims to provide useful insights to improve the entire pathway of a patient undergoing cataract surgery, from the preoperative setting to the postoperative one. The available evidence from main clinical trials published on this topic is presented in association with experience-based points of view by the authors. Ocular surface disease (OSD) is common in patients presenting for cataract surgery, and more than half of these patients have DED and meibomian gland dysfunction (MGD), even in the absence of symptoms. Therefore, there is a need to encourage preoperative assessments for the risk of DED development or worsening in all patients as a routine approach to cataract surgery. New all-in-one diagnostic machines allow for fast and noninvasive screening of the ocular surface status. Once a preoperative diagnosis of DED/OSD is reached, ocular surface optimization should be obtained before surgery. In the case of unresolved OSD, the decision to delay surgery should be considered. The surgical procedure can be optimized by avoiding large incisions, limiting microscope light intensity and exposure, and avoiding an aspirating speculum or preserved eye drops. Postoperatively, the continued avoidance of preserved agents is advisable, as well as a limited exposure to epitheliotoxic antibiotics and nonsteroidal anti-inflammatory drugs. Short-term, preservative-free, soft corticosteroids may be useful for patients with extensive or persistent inflammation.

2.
Eur J Ophthalmol ; : 11206721231222947, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38153338

RESUMO

BACKGROUND: Diabetes mellitus is associated with increased risk of ocular surface diseases in elderly. We consider neutrophil CD15 as a potential marker of ocular surface damage in type II diabetes mellitus patients. AIM: We aimed to evaluate expression of neutrophil CD15 and correlate it with results of conjunctival impression cytology and routine objective anterior ocular surface tests (TMH, NIBUT, LLT, MGD) in T2DM patients. MATERIALS AND METHODS: We prospectively enrolled sixty type II diabetes mellitus patients (120 eyes) into a study group. The control group included forty (80 eyes) age- and sex-matched healthy individuals. All patients underwent comprehensive ophthalmological examination, and tear meniscus height test (TMH), noninvasive tear break-up time (NIBUT), lipid layer thickness measurement (LLT), Meibomian gland dysfunction evaluation (MGD), conjunctival impression cytology (CIC) and expression of CD15. RESULTS: Abnormal Nelson's grades of squamous metaplasia (grades 2 and 3) were observed in 50% (60 eyes) of the study group, and 13.8 (11 eyes) of the control group. Fifteen patients with type II diabetes mellitus suffered from grade 3 squamous metaplasia. Nelson's grades of squamous metaplasia have shown a positive correlation with the level of CD15 expression either in the study and control groups (rs = 0.628, p = <0.0001; rs = 0.746, p < 0.0001; respectively). CONCLUSIONS: The research shows significantly reduced values of routine objective ocular tests in type II diabetes mellitus patients in comparison to healthy participants older than 60 y.o. Increased CD15 in the peripheral blood is associated with the development of squamous metaplasia and may be used to evaluate the severity of ocular surface damage in type II diabetes mellitus patients.

3.
Ocul Surf ; 28: 165-199, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37062429

RESUMO

Societal factors associated with ocular surface diseases were mapped using a framework to characterize the relationship between the individual, their health and environment. The impact of the COVID-19 pandemic and mitigating factors on ocular surface diseases were considered in a systematic review. Age and sex effects were generally well-characterized for inflammatory, infectious, autoimmune and trauma-related conditions. Sex and gender, through biological, socio-economic, and cultural factors impact the prevalence and severity of disease, access to, and use of, care. Genetic factors, race, smoking and co-morbidities are generally well characterized, with interdependencies with geographical, employment and socioeconomic factors. Living and working conditions include employment, education, water and sanitation, poverty and socioeconomic class. Employment type and hobbies are associated with eye trauma and burns. Regional, global socio-economic, cultural and environmental conditions, include remoteness, geography, seasonality, availability of and access to services. Violence associated with war, acid attacks and domestic violence are associated with traumatic injuries. The impacts of conflict, pandemic and climate are exacerbated by decreased food security, access to health services and workers. Digital technology can impact diseases through physical and mental health effects and access to health information and services. The COVID-19 pandemic and related mitigating strategies are mostly associated with an increased risk of developing new or worsening existing ocular surface diseases. Societal factors impact the type and severity of ocular surface diseases, although there is considerable interdependence between factors. The overlay of the digital environment, natural disasters, conflict and the pandemic have modified access to services in some regions.


Assuntos
COVID-19 , Pandemias , Masculino , Feminino , Humanos , COVID-19/epidemiologia , Fatores Socioeconômicos , Pobreza , Estilo de Vida
4.
Ocul Immunol Inflamm ; 30(7-8): 1816-1824, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34379560

RESUMO

PURPOSE: To develop an in vitro model of severe immunocompetent-dry eye disease (ic-DED) and to investigate the mechanism of action of a T-lysial ocular surface modulator. MATERIALS AND METHODS: The reconstructed human corneal epithelium (HCE) was exposed to dryness stimuli. THP-1 cell infiltration into HCE was monitored at 4 h and 24 h from T-lysial application by immunohistochemistry (CD14, CD86, AQP3) and molecular biology (AQP3, TLR4 and TNF-α). RESULTS: A reduction of CD14, CD86 and AQP3 was observed after T-lysial treatment at 24 h. TLR4 was overexpressed in ic-DED model and downregulated by T-Lysial after 24 h. TNF-α expression was not modified. CONCLUSION: The ic-DED model can be used to monitor the migration and differentiation of THP-1 into HCE. T-lysial was found to exert anti-inflammatory activity. This experimental model is a promising tool to study the crosstalk between epithelial and immune cells, providing new insights on the mechanisms of DED onset.


Assuntos
Síndromes do Olho Seco , Fator de Necrose Tumoral alfa , Humanos , Biologia Molecular , Síndromes do Olho Seco/tratamento farmacológico
5.
Cornea ; 38(6): 698-705, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30844839

RESUMO

PURPOSE: To investigate the expression levels of inflammatory cytokines in the conjunctival epithelium and correlations with clinical parameters in dry eye disease (DED). METHODS: This study evaluated 28 patients with Sjögren syndrome (SS) DED, 28 patients with non-SS DED, and 10 controls. The messenger ribonucleic acid (mRNA) expression of inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, interferon (IFN)-γ, IL-17, and matrix metalloproteinase 9 (MMP9) from conjunctival epithelium was investigated by real-time polymerase chain reaction. Protein expression was confirmed by immunofluorescence staining. Correlations were evaluated between the mRNA expression of inflammatory cytokines and clinical DED parameters such as ocular surface disease index score, Schirmer I value, tear film breakup time, and corneal and conjunctival staining scores. RESULTS: Patients with non-SS DED expressed significantly more IFN-γ, IL-6, and MMP9 genes in the conjunctival epithelium than the controls (P < 0.05), and all cytokine gene expression was significantly higher in patients with SS DED than in the controls (P < 0.01). Tumor necrosis factor-α, IL-1ß, IL-6, and IL-17 gene expression was higher in patients with SS DED than in the non-SS DED group (P < 0.05). Immunofluorescence staining of conjunctival epithelium demonstrated that positive cells with IL-6 or MMP9 were significantly higher in non-SS DED than in controls (P < 0.01) and much higher in SS DED than in non-SS DED (P < 0.05). Conjunctival staining scores significantly correlated with the expression of IFN-γ, IL-6, IL-17, and MMP9 in both DED groups (P < 0.05 in non-SS DED and P < 0.01 in SS-DED). Interestingly, correlation coefficients of all cytokines were much higher in SS DED compared to non-SS DED. Corneal staining scores showed positive correlations with IFN-γ, IL-17, and MMP9 (P < 0.05), and correlation coefficients were lower than those of conjunctival staining scores. CONCLUSIONS: Conjunctival staining scores may be useful to measure ocular surface inflammation in SS and non-SS DED.


Assuntos
Túnica Conjuntiva/metabolismo , Edema da Córnea/metabolismo , Citocinas/metabolismo , Síndromes do Olho Seco/metabolismo , Síndrome de Sjogren/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Epitélio/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Ocul Immunol Inflamm ; 27(3): 507-512, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29308960

RESUMO

Increasing resistance to antimicrobial agents has contributed to an elevated risk of complications of infectious keratitis. Corneal collagen cross-linking (CXL) has been widely adopted for the management of keratoconus and post-refractive surgery corneal ectasia. It has recently been introduced as an option for treating keratitis due to multidrug resistant organisms. The purpose of this review is to discuss the rationale, safety, and evidence for CXL in infectious keratitis and its possible effect on ocular surface inflammation. Published data show that CXL is effective and safe as an adjunct to antibiotic treatment in selected cases of bacterial keratitis. The benefit of CXL probably varies according to the etiology of the infection.


Assuntos
Colágeno/farmacologia , Reagentes de Ligações Cruzadas/farmacologia , Infecções Oculares Bacterianas/tratamento farmacológico , Ceratite/tratamento farmacológico , Fotoquimioterapia/métodos , Infecções Oculares Bacterianas/microbiologia , Humanos , Ceratite/microbiologia , Fármacos Fotossensibilizantes/uso terapêutico , Raios Ultravioleta
7.
Ocul Surf ; 14(3): 365-76, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27224876

RESUMO

Dry eye disease (DED) is one of the most common reasons for patients (particularly those over the age of 50) to seek ophthalmic care. There is a wide array of causes for DED that can induce an alteration of the ocular surface system and determine the chronicity of the disease, including low blink rates (eg, computer use), systemic and topical drugs, autoimmune diseases, contact lens wear, and cataract and refractive surgery. Patients with dry eye experience numerous symptoms that can reduce their productivity and overall quality of life. This article presents the results of a roundtable focused on patients' symptoms. The goal was to better understand the symptoms reported by patients, the possible effects on visual function, the consequences on the quality of life, and the methodologies that can be used to measure and monitor symptoms in clinical practice and in clinical studies. The discrepancies between clinical signs and symptoms reported in some cases are considered in the context of the ocular surface system.


Assuntos
Síndromes do Olho Seco , Piscadela , Lentes de Contato , Humanos , Ceratoconjuntivite Seca , Qualidade de Vida
8.
Exp Eye Res ; 134: 80-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25817729

RESUMO

We aimed to determine if toll-like receptor (TLR) expression is modulated in response to dry eye-associated conditions and in dry eye syndrome (DES). Primary human corneal epithelial cells (HCEC), an SV40 HCEC cell line or a normal human conjunctival epithelial cell line (IOBA-NHC) were cultured under hyperosmolar stress (HOS) (400-500 mOsm/kg) or with DES associated cytokines (IL-1α/ß, TNFα or TGFß) at concentrations ranging from 1 to 1000 ng/ml for up to 24 h. Epithelial cells were harvested from a human cornea organ culture model following 24 h of desiccation. Conjunctival impression cytology samples were harvested from subjects with DES and age and gender-matched normal subjects. TLR4, TLR5 or TLR9 mRNA or protein was examined by quantitative RT-PCR, western blotting or flow cytometry. TLR functionality was evaluated in terms of addition of TLR agonists and quantitation of secreted inflammatory cytokines by the use of ELISA and Luminex assays. In SV40 HCEC, HOS significantly increased TLR4 by 8.18 fold, decreased TLR9 by 0.58 fold, but had no effect on TLR5 mRNA expression. TLR4 and TLR9 protein were decreased by 67.7% and 72% respectively. TLR4 mRNA was also significantly up-regulated by up to 9.70 and 3.36 fold in primary HCEC and IOBA-NHC respectively. DES associated cytokines had no effect on TLR4, TLR5 and TLR9 expression. In response to desiccation, TLR4 and TLR5 mRNA were significantly up-regulated by 4.81 and 2.51 fold respectively, while TLR9 mRNA was down-regulated by 0.86 fold in HCEC. A similar trend for TLR4 and TLR9 protein was observed. TLR9 mRNA was significantly down-regulated by almost 59.5% in DES subjects. In conclusion, changes in TLR expression occur in dry eye and could have an important role in ocular surface susceptibility to inflammation and infection.


Assuntos
Túnica Conjuntiva/citologia , Síndromes do Olho Seco/metabolismo , Células Epiteliais/metabolismo , Epitélio Corneano/metabolismo , Receptores Toll-Like/metabolismo , Adulto , Idoso , Western Blotting , Células Cultivadas , Citocinas/farmacologia , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/efeitos dos fármacos , Epitélio Corneano/efeitos dos fármacos , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , Pressão Osmótica , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Receptor 5 Toll-Like/genética , Receptor 5 Toll-Like/metabolismo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Receptores Toll-Like/genética
9.
Exp Eye Res ; 127: 153-60, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25084452

RESUMO

Researchers have proposed that estrogen deficiency will lead to a Sjögren's syndrome (SjS)-like lacrimal gland inflammation, aqueous tear deficiency and dry eye. The purpose of this study was to determine whether this proposal is correct. Lacrimal glands were obtained from adult, age-matched wild type (WT) and aromatase knockout (ArKO) mice, in which estrogen synthesis is completely eliminated. Tissues were also obtained from autoimmune MRL/Mp-lpr/lpr (MRL/lpr) mice as inflammation controls. Tear volumes in WT and ArKO mice were measured and glands were processed for molecular biological and histological evaluation. Our results demonstrate that estrogen absence does not lead to a SjS-like inflammation in lacrimal tissue or to an aqueous-deficient dry eye. There was no upregulation of genes associated with inflammatory pathways in lacrimal glands of male or female ArKO mice. Such inflammatory activity was prominent in autoimmune MRL/lpr tissues. We also found no evidence of inflammation in lacrimal gland tissue sections of estrogen-deficient mice, and tear volumes of ArKO males were actually increased as compared to those WT controls. Interestingly, our study did show that estrogen absence influences the expression of thousands of lacrimal gland genes, and that this impact is sex- and genotype-specific. Our findings demonstrate that estrogen absence is not a risk factor for the development of SjS-like lacrimal gland inflammation or for aqueous-deficient dry eye in mice.


Assuntos
Humor Aquoso/metabolismo , Dacriocistite/metabolismo , Síndromes do Olho Seco/metabolismo , Estrogênios/deficiência , Animais , Aromatase/genética , Dacriocistite/genética , Dacriocistite/patologia , Síndromes do Olho Seco/genética , Síndromes do Olho Seco/patologia , Proteínas do Olho/genética , Feminino , Expressão Gênica/fisiologia , Genótipo , Aparelho Lacrimal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Camundongos Knockout , Reação em Cadeia da Polimerase , Fatores Sexuais , Regulação para Cima
10.
Biol Cell ; 105(8): 345-58, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23659850

RESUMO

BACKGROUND INFORMATION: The rod outer segment (OS) is the specialised organelle where phototransduction takes place. Our previous proteomic and biochemical analyses on purified rod disks showed the functional expression of the respiratory chain complexes I-IV and F1 Fo -ATP synthase in OS disks, as well as active soluble tricarboxylic acid cycle enzymes. Here, we focussed our study on the whole OS that contains the cytosol and plasma membrane and disks as native flattened saccules, unlike spherical osmotically intact disks. RESULTS: OS were purified from bovine retinas and characterised for purity. Oximetry, ATP synthesis and cytochrome c oxidase (COX) assays were performed. The presence of COX and F1F0-ATP synthase (ATP synthase) was assessed by semi-quantitative Western blotting, immunofluorescence or confocal laser scanning microscopy on whole bovine retinas and bovine retinal sections and by immunogold transmission electron microscopy (TEM) of purified OS or bovine retinal sections. Both ATP synthase and COX are catalytically active in OS. These are able to consume oxygen (O2) in the presence of pyruvate and malate. CLSM analyses showed that rhodopsin autofluorescence and MitoTracker Deep Red 633 fluorescence co-localise on rod OS. Data are confirmed by co-localisation studies of ATP synthase with Rh in rod OS by immunofluorescence and TEM in bovine retinal sections. CONCLUSIONS: Our data confirm the expression and activity of COX and ATP synthase in OS, suggestive of the presence of an extra-mitochondrial oxidative phosphorylation in rod OS, meant to supply ATP for the visual transduction. In this respect, the membrane rich OS environment would be meant to absorb both light and O2. The ability of OS to manipulate O2 may shed light on the pathogenesis of many retinal degenerative diseases ascribed to oxidative stress, as well as on the efficacy of the treatment with dietary supplements, presently utilised as supporting therapies.


Assuntos
Trifosfato de Adenosina/metabolismo , Doenças Retinianas/metabolismo , Segmento Externo da Célula Bastonete/metabolismo , Animais , Bovinos , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Oxigênio/metabolismo , Fosforilação , Retina/metabolismo , Doenças Retinianas/enzimologia , Segmento Externo da Célula Bastonete/enzimologia
11.
Curr Eye Res ; 35(8): 665-9, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20673042

RESUMO

PURPOSE: To evaluate and compare HLA-DR expression of conjunctival epithelial cells in different grade of conjunctivochalasis (CCh). PATIENTS AND METHODS: Thirty patients and seven healthy subjects underwent clinical examination, grading of CCh by lid-parallel conjunctival fold (LIPCOF) test, and impression cytology of the bulbar conjunctiva. HLA-DR expression was analyzed by flow cytometry. Schirmer test, tear break-up time, and vital staining were also performed. RESULTS: Patients who presented with mild and moderate CCh showed a similar expression of HLA-DR to normal subjects. A significant increase (p < 0.005) of HLA-DR was found in patients with severe CCh. Positive correlation was found between fluorescein staining and HLA-DR expression (r = 0.36, p = 0.009) and between lissamine-green staining and HLA-DR expression (r = 0.30, p = 0.027). Neither correlation was found between Schirmer test nor break up time and HLA-DR expression. CONCLUSION: Inflammation plays a pivotal role on the ocular surface of patients with severe CCh. Since mild and moderate CCh HLA-DR expression was similar to normal controls, we can speculate that the source of inflammation could be the presence of conjunctival folds.


Assuntos
Túnica Conjuntiva/metabolismo , Doenças da Túnica Conjuntiva/metabolismo , Células Epiteliais/metabolismo , Antígenos HLA-DR/metabolismo , Biomarcadores/metabolismo , Corantes/metabolismo , Túnica Conjuntiva/patologia , Doenças da Túnica Conjuntiva/classificação , Doenças da Túnica Conjuntiva/patologia , Células Epiteliais/patologia , Feminino , Citometria de Fluxo , Humanos , Inflamação/metabolismo , Corantes Verde de Lissamina/metabolismo , Masculino , Pessoa de Meia-Idade , Coloração e Rotulagem
12.
Int J Biochem Cell Biol ; 41(12): 2555-65, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19715769

RESUMO

The disks of the vertebrate retinal rod Outer Segment (OS), devoid of mitochondria, are the site of visual transduction, a very energy demanding process. In a previous proteomic study we reported the expression of the respiratory chain complexes I-IV and the oxidative phosphorylation Complex V (F(1)F(0)-ATP synthase) in disks. In the present study, the functional localization of these proteins in disks was investigated by biochemical analyses, oxymetry, membrane potential measurements, and confocal laser scanning microscopy. Disk preparations, isolated by Ficoll flotation, were characterized for purity. An oxygen consumption, stimulated by NADH and Succinate and reverted by rotenone, antimycin A and KCN was measured in disks, either in coupled or uncoupled conditions. Rhodamine-123 fluorescence quenching kinetics showed the existence of a proton potential difference across the disk membranes. Citrate synthase activity was assayed and found enriched in disks with respect to ROS. ATP synthesis by disks (0.7 micromol ATP/min/mg), sensitive to the common mitochondrial ATP synthase inhibitors, would largely account for the rod ATP need in the light. Overall, data indicate that an oxidative phosphorylation occurs in rod OS, which do not contain mitochondria, thank to the presence of ectopically located mitochondrial proteins. These findings may provide important new insight into energy production in outer segments via aerobic metabolism and additional information about protein components in OS disk membranes.


Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Segmento Externo das Células Fotorreceptoras da Retina/enzimologia , Células Fotorreceptoras Retinianas Bastonetes/enzimologia , Aerobiose , Animais , Antimicina A/farmacologia , Bovinos , Respiração Celular/efeitos dos fármacos , Células Cultivadas , Transporte de Elétrons/fisiologia , Microscopia Confocal , ATPases Mitocondriais Próton-Translocadoras , NAD/farmacologia , Fosforilação Oxidativa , Consumo de Oxigênio/efeitos dos fármacos , Cianeto de Potássio/farmacologia , Células Fotorreceptoras Retinianas Bastonetes/ultraestrutura , Rotenona/farmacologia , Desacopladores/farmacologia
13.
Ophthalmic Surg Lasers Imaging ; 39(6): 511-3, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19065986

RESUMO

Pterygium is a frequent ocular surface disorder of unknown origin characterized by chronic conjunctival inflammation with a clear central cornea in most patients. A 35-year-old man affected by pterygium in the right eye presented with unremarkable slit-lamp examination of the central cornea, in which in vivo confocal microscopy showed a significant alteration of the superficial epithelial cells, numerous dendritic-like cells in the basal epithelial layer, and loss of keratocytes in the stroma. In vivo confocal microscopy may be helpful in evaluating the immunological and structural changes of the cornea in patients with pterygium and in understanding its pathophysiology.


Assuntos
Substância Própria/patologia , Epitélio Corneano/patologia , Microscopia Confocal , Pterígio/diagnóstico , Adulto , Humanos , Masculino
14.
Arch Ophthalmol ; 126(2): 219-25, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18268213

RESUMO

OBJECTIVE: To study the efficacy of topical application of alpha-linolenic acid (ALA) and linoleic acid (LA) for dry eye treatment. METHODS: Formulations containing ALA, LA, combined ALA and LA, or vehicle alone, were applied to dry eyes induced in mice. Corneal fluorescein staining and the number and maturation of corneal CD11b(+) cells were determined by a masked observer in the different treatment groups. Real-time polymerase chain reaction was used to quantify expression of inflammatory cytokines in the cornea and conjunctiva. RESULTS: Dry eye induction significantly increased corneal fluorescein staining; CD11b(+) cell number and major histocompatibility complex Class II expression; corneal IL-1alpha and tumor necrosis factor alpha (TNF-alpha) expression; and conjunctival IL-1alpha, TNF-alpha, interferon gamma, IL-2, IL-6, and IL-10 expression. Treatment with ALA significantly decreased corneal fluorescein staining compared with both vehicle and untreated controls. Additionally, ALA treatment was associated with a significant decrease in CD11b(+) cell number, expression of corneal IL-1alpha and TNF-alpha, and conjunctival TNF-alpha. CONCLUSIONS: Topical ALA treatment led to a significant decrease in dry eye signs and inflammatory changes at both cellular and molecular levels. CLINICAL RELEVANCE: Topical application of ALA omega-3 fatty acid may be a novel therapy to treat the clinical signs and inflammatory changes accompanying dry eye syndrome.


Assuntos
Síndromes do Olho Seco/tratamento farmacológico , Ácido Linoleico/administração & dosagem , Soluções Oftálmicas/administração & dosagem , Ácido alfa-Linolênico/administração & dosagem , Administração Tópica , Animais , Antígeno CD11b/metabolismo , Contagem de Células , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/metabolismo , Córnea/efeitos dos fármacos , Córnea/metabolismo , Citocinas/genética , Modelos Animais de Doenças , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/patologia , Fluoresceína/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/metabolismo , Monócitos/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do Tratamento
15.
Arch Ophthalmol ; 125(7): 908-15, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17620569

RESUMO

OBJECTIVE: To determine whether the ocular anterior segment (aqueous humor and cornea) actively inhibits dendritic cell (DC) maturation. METHODS: Dendritic cells were injected into syngeneic corneas or conjunctivae, and their surface major histocompatibility complex class II expression in response to the local milieu was assessed using confocal microscopy. Immature DCs were cocultured with corneal supernatant or with aqueous humor to evaluate their regulation of DC phenotypic and functional maturity. RESULTS: In contrast to conjunctivally injected DCs, DCs injected into the cornea resisted up-regulation in expression of surface major histocompatibility complex class II. Corneal supernatant-treated and aqueous humor-treated DCs retained their immaturity, as reflected by high antigen uptake but low costimulatory molecule (CD80 and CD86) expression and poor T-cell stimulation. Anti-transforming growth factor beta(2) treatment of aqueous humor and of corneal supernatant led to complete and partial blockade of their inhibition of DC maturation, respectively. However, alpha-melanocyte-stimulating hormone and calcitonin gene-related peptide had no demonstrable effect on DC maturation. CONCLUSION: Cornea and aqueous humor, principally through transforming growth factor beta(2,) promote generation of phenotypically and functionally immature DCs. Clinical Relevance Our results indicate that relative immune quiescence in the cornea and in the anterior segment is actively maintained in part by the inhibitory effect of transforming growth factor beta(2) on resident DCs and by their suppression of T-cell-mediated immune and inflammatory responses.


Assuntos
Diferenciação Celular/fisiologia , Córnea/imunologia , Células Dendríticas/citologia , Animais , Humor Aquoso/fisiologia , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Células da Medula Óssea/citologia , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Técnicas de Cocultura , Células Dendríticas/imunologia , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe II/metabolismo , Teste de Cultura Mista de Linfócitos , Complexo Principal de Histocompatibilidade , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microscopia Confocal , Microscopia de Fluorescência , Fenótipo , Fator de Crescimento Transformador beta2/farmacologia , alfa-MSH/farmacologia
16.
Transplantation ; 81(11): 1577-82, 2006 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-16770247

RESUMO

BACKGROUND: Murine models of high-risk and low-risk corneal transplantation were used to determine the role of keratocyte apoptosis in the failure of orthotopic allogeneic corneal transplants. MATERIALS AND METHODS: Normal (low-risk, low-rejecting) and inflamed/vascularized (high-risk, high-rejecting) BALB/c recipient beds received fully mismatched C57BL/6 corneal allografts. Apoptosis was detected in the corneal stroma at various time points using an in situ terminal deoxynucleotide tranferase-mediated dUTP nick-end labeling assay, and ex vivo via Western analysis for active caspase-3. Apoptosis was also measured in a (donor-type) C57BL/6 keratocyte cell line after stimulation of Fas or via use of various pro-inflammatory cytokines. RESULTS: Significantly more apoptotic cells were present in the stroma of rapidly rejecting high-risk corneal allografts compared with low-risk grafts. Apoptotic cells were shown to be nearly uniformly CD45 and hence of a non-hematopoetic lineage. Apoptosis, however, was not present in highly inflamed but ungrafted corneas. Apoptosis was induced in keratocytes in vitro by dual stimulation with agonistic Fas mAb and either interleukin-1beta or tumor necrosis factor-alpha. CONCLUSION: Apoptosis of resident non-bone marrow-derived fibroblastic cells of the corneal stroma is strongly correlated with the failure of corneal allografts, particularly in the highly inflamed microenvironment of the high-risk allograft.


Assuntos
Apoptose/fisiologia , Substância Própria/citologia , Substância Própria/transplante , Transplante de Córnea/imunologia , Fibroblastos/fisiologia , Rejeição de Enxerto/fisiopatologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Caspase 3 , Caspases/análise , Linhagem Celular , Fibroblastos/enzimologia , Imunofluorescência , Rejeição de Enxerto/patologia , Inflamação/patologia , Inflamação/fisiopatologia , Interleucina-1/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Receptores do Fator de Necrose Tumoral/imunologia , Transplante Homólogo/patologia , Transplante Homólogo/fisiologia , Fator de Necrose Tumoral alfa/farmacologia , Receptor fas
18.
Cornea ; 24(8): 909-14, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16227831

RESUMO

Today radiation is routinely used as a therapeutic modality for select tumors of the orbit, adnexa, paranasal sinus, and nasopharynx. Despite significant improvements in mechanisms of delivery and protective shielding, acute and chronic complications of radiation can affect different segments of the eye. In this report, we provide an overview of ocular damage secondary to radiotherapy. We identify the characteristic clinical changes and underlying pathophysiologic mechanisms involving the ocular surface and provide a rational approach to their prevention and treatment.


Assuntos
Oftalmopatias/etiologia , Olho/efeitos da radiação , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Neoplasias Oculares/radioterapia , Humanos , Fatores de Risco , Índice de Gravidade de Doença
19.
Invest Ophthalmol Vis Sci ; 46(8): 2766-71, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16043849

RESUMO

PURPOSE: To develop a controlled-environment chamber (CEC) for mice and verify the effects of a low-humidity setting on ocular surface signs in normal mice. METHODS: Eight- to 12-week-old BALB/c mice were used in a controlled-environment chamber (CEC) where relative humidity (RH), temperature (T), and airflow (AF) are regulated and monitored. Mice were placed into the CEC and exposed to specific environmentally controlled conditions (RH = 18.5% +/- 5.1%, AF = 15 L/min, T = 21-23 degrees C) for 3, 7, 14, and 28 days. Control mice were kept in a normal environment (RH = 50%-80%, no AF, T = 21-23 degrees C) for the same duration. Aqueous tear production by means of the cotton thread test, corneal fluorescein staining (score, 0-15), and goblet cell density in the superior and inferior conjunctiva were measured by a masked observer. RESULTS: No statistically significant differences between the groups were found at baseline. Decreased tear secretion and increased corneal fluorescein staining were significantly present on day 3, 7, 14, and 28 in animals kept in the CEC. Goblet cell density was significantly decreased in the superior conjunctiva on day 7, and on day 3, 7, and 14 in the inferior conjunctiva in the CEC-kept mice compared with control animals. CONCLUSIONS: This study indicates that exposure of normal mice to a low-humidity environment in a CEC can lead to significant alterations in tear secretion, goblet cell density, and acquisition of dry eye-related ocular surface signs.


Assuntos
Câmaras de Exposição Atmosférica/efeitos adversos , Modelos Animais de Doenças , Síndromes do Olho Seco/etiologia , Ambiente Controlado , Ar , Animais , Contagem de Células , Túnica Conjuntiva/patologia , Córnea/patologia , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/patologia , Células Epiteliais/patologia , Feminino , Fluoresceína , Células Caliciformes/patologia , Umidade , Camundongos , Camundongos Endogâmicos BALB C , Coloração e Rotulagem , Lágrimas/metabolismo , Temperatura
20.
J Refract Surg ; 21(3): 288-93, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15977887

RESUMO

PURPOSE: To evaluate the safety and efficacy of automated lamellar keratoplasty for the treatment of recurrent granular corneal dystrophy after phototherapeutic keratectomy (PTK). METHODS: We performed a prospective interventional noncomparative case study of nine eyes (seven patients) with severe recurrent granular corneal dystrophy after PTK. An automated microkeratome was used to cut partial-thickness sections through the anterior surface of the donor and host corneas. The donor disc was placed on the recipient bed with four or eight interrupted sutures. The sutures were removed between 4 and 6 weeks postoperatively. Visual acuity, corneal clarity, corneal thickness, and corneal topography were assessed before and at different time points after surgery. RESULTS: During a mean follow-up period of 18.9 +/- 4.1 months, all grafts were transparent without visible opacity at the interface, and no serious complications occurred. In all cases, the visual acuity improved: seven eyes had best spectacle-corrected visual acuity of > or = 20/40; two eyes reached 20/25. At last follow-up > 12 months postoperatively, the mean corneal refractive power had significantly increased by 2.34 +/- 0.93 diopters (D) (P<.001), and the corneal astigmatism significantly decreased by 0.91 +/- 0.98 D (P<.05). The mean corneal thickness was 477.4 +/- 26.9 microm preoperatively and 507.8 +/- 23.4 microm at last follow-up (P<.001). CONCLUSIONS: Our findings suggest that automated lamellar keratoplasty for the treatment of recurrent granular corneal dystrophy is a safe and effective method of improving visual acuity, but recurrence remains a risk.


Assuntos
Distrofias Hereditárias da Córnea/cirurgia , Transplante de Córnea/métodos , Ceratectomia Fotorrefrativa , Adulto , Distrofias Hereditárias da Córnea/etiologia , Topografia da Córnea , Feminino , Sobrevivência de Enxerto , Humanos , Lasers de Excimer , Masculino , Estudos Prospectivos , Recidiva , Segurança , Acuidade Visual
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