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1.
Klin Monbl Augenheilkd ; 230(2): 127-32, 2013 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-23335086

RESUMO

Prostaglandin and prostamide analogues belong to a new substance group which came into the market in the 1990s. They have revolutionised antiglaucomatous therapy by their once-daily dosing regimen and fewer side effects. Today, prostaglandin and prostamide analogues are approved as first-line therapy for patients with primary open-angle glaucoma and ocular hypertension. They lower the intraocular pressure primarily by increasing the uveoscleral outflow. Recent investigations have shown that they also improve the trabecular outflow facility and thus the conventional outflow pathways. Prostaglandin and prostamide analogues are highly efficient in lowering the intraocular pressure, for which they are superior to other antiglaucomatous substance groups. In particular, they appear to have a good control of 24-hour intraocular pressure fluctuations by primarily improving the outflow pathways. Furthermore, they have less systemic side effects than ß-blockers. However, their use is often associated with higher costs. In case of undesirable events, they mostly present with ocular symptoms. Based on their good clinical profile, prostaglandin and prostamide analogues play an important role in the primary and additive therapy for glaucoma.


Assuntos
Anti-Hipertensivos/uso terapêutico , Dinoprostona/análogos & derivados , Dinoprostona/uso terapêutico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/fisiopatologia , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/fisiopatologia , Prostaglandinas Sintéticas/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/economia , Análise Custo-Benefício , Dinoprostona/economia , Custos de Medicamentos/estatística & dados numéricos , Quimioterapia Combinada , Humanos , Prostaglandinas Sintéticas/efeitos adversos , Prostaglandinas Sintéticas/economia
2.
Klin Monbl Augenheilkd ; 227(2): 99-107, 2010 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-20155653

RESUMO

Primary open angle glaucoma (POAG) is defined as an optic neuropathy which is characterised by the loss of optic nerve axons and the related retinal ganglion cells. The reason for these changes is still unknown. In the pathogenesis of POAG several factors like increased intraocular pressure and a reduction of ocular blood supply are discussed. Morphological and biochemical analyses of the trabecular meshwork (TM) of POAG patients revealed loss of cells, increased accumulation of extracellular matrix (ECM), changes in the cytoskeleton, cellular senescence and the process of subclinical inflammation. One factor becoming more likely to be involved in the pathogenesis of POAG is oxidative stress. Treatment of TM cells with oxidative stress induced POAG-typical changes like ECM accumulation, cell death, disarrangement of the cytoskeleton, advanced senescence and the release of inflammatory markers. By pretreatment with antioxidants, prostaglandin analogues, beta-blockers or local carbonic anhydrase inhibitors, these effects were markedly reduced. In conclusion, oxidative stress is able to induce characteristic glaucomatous TM changes in vitro and these oxidative stress-induced TM changes can be minimised by the use of antioxidants and IOP-lowering substances. It is tempting to speculate that prevention of oxidative stress exposure to the TM may help to reduce the progression of POAG.


Assuntos
Glaucoma de Ângulo Aberto/fisiopatologia , Estresse Oxidativo/fisiologia , Malha Trabecular/fisiopatologia , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/patologia , Citoesqueleto/fisiologia , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/patologia , Matriz Extracelular/fisiologia , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/patologia , Humanos , Mediadores da Inflamação/metabolismo , Microscopia Eletrônica , Neuropatia Óptica Isquêmica/tratamento farmacológico , Neuropatia Óptica Isquêmica/patologia , Neuropatia Óptica Isquêmica/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fatores de Risco , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/patologia
3.
Klin Monbl Augenheilkd ; 225(6): 548-54, 2008 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-18516775

RESUMO

An intact retinal pigment epithelium (RPE) represents an essential condition for the visual process. This post-mitotic RPE monolayer combines different functions such as degradation of photoreceptor outer segments, vitamin A cycle, support of retinal metabolism and maintenance of the outer blood-retina barrier. As a consequence of excessive metabolism, high oxygen levels, exposition to light of short wave length and ensuing radical formation, the RPE is highly dependent on protective systems. In spite of differentiated defence mechanisms, aging processes cause cumulative RPE damage, representing a major component of age-related macular degeneration (AMD), the leading cause of irreversible severe vision loss in people over 50 years old. A better understanding of the underlying pathophysiology will help to develop new prophylactic options which is becoming more and more important with increasing life expectancy.


Assuntos
Degeneração Macular/prevenção & controle , Degeneração Macular/fisiopatologia , Epitélio Pigmentado Ocular/fisiopatologia , Antioxidantes/administração & dosagem , Barreira Hematorretiniana/fisiologia , Metabolismo Energético/fisiologia , Ácidos Graxos Ômega-3/administração & dosagem , Glutationa/fisiologia , Humanos , Lipofuscina/metabolismo , Consumo de Oxigênio/fisiologia , Segmento Externo da Célula Bastonete/fisiopatologia , Superóxidos/metabolismo , Oligoelementos/administração & dosagem , Acuidade Visual/fisiologia
4.
Ophthalmologe ; 104(11): 965-71, 2007 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-17653724

RESUMO

OBJECTIVE: Intravitreal anti-vascular endothelial growth factor (VEGF) treatment with bevacizumab (Avastin) has emerged as a promising therapy for the treatment of choroidal neovascularisation in age-related macular degeneration. Intravitreal administration of bevacizumab is "off-label," and only very limited data regarding short-term toxicity exist. Therefore, we investigated the safety of different doses of bevacizumab on the anterior- and posterior-segment cells of the human eye. METHODS: Primary human retinal pigment epithelium (RPE) cells, human optic nerve head astrocytes (ONHA), human trabecular meshwork cells (TMC), and cornea buttons not suitable for transplantation were treated with bevacizumab (25 microg/ml, 250 microg/ml, and 2,500 microg/ml) for 48 h, corresponding to 0.1x, 1x, and 10x the dosage used intravitreally. Bevacizumab-related toxicity was evaluated by a colorimetric test (MTT) measuring inhibition of RPE, ONHA, and TMC cell proliferation. Additionally, cell viability was quantified by live/dead fluorescence assay. Corneal endothelium was quantified by phase-contrast microscopy. RESULTS: Bevacizumab showed adverse effects on primary RPE cell proliferation as well as on cell viability at a concentration of 2,500 microg/ml. The lower concentrations of 25 microg/ml and 250 microg/ml had no influence on RPE cell proliferation or cell viability. There was no toxicity for any investigated concentration on human ONHA, TMC, or corneal endothelium. CONCLUSION: In this study, a 10-fold concentration (compared with common clinical use) of the VEGF-blocking antibody bevacizumab had toxic effects on primary RPE. There was no toxicity for lower concentrations or toxicity to other cell types of the anterior and posterior segments. Therefore, the clinical use of bevacizumab at concentrations of 1-1.25 mg intravitreally seems to be safe.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Olho/citologia , Olho/efeitos dos fármacos , Anticorpos Monoclonais Humanizados , Bevacizumab , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos
5.
Ophthalmologe ; 102(3): 251-8, 2005 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-15351898

RESUMO

BACKGROUND: The RTA features a fundus photography mode and optic disc topography. Those two new modes were investigated regarding their clinical use. METHODS: First, the combination of wide-field photography with a retinal thickness map was assessed for tele-screening for diabetic retinopathy in 31 eyes. Second, normal values of the optic disc were collected on 30 non-glaucomatous probands in the non-mydriatic mode and compared to the results of the mydriatic mode, for which reproducibility was also investigated. RESULTS: For diabetic retinopathy, the RTA yielded mean 93% sensitivity for proliferative diabetic retinopathy and 100% sensitivity for detecting diabetic macular edema compared to clinical examination at specificities ranging from 58 to 96%. Regarding the measurements of the optic disc, the normal values in mydriasis coincided with those in miosis in all but 4 of 12 parameters. CONCLUSIONS: The RTA is suitable for application in tele-screening for diabetic retinopathy. The topography of the optic disc is highly reproducible and may be used for glaucoma diagnostics.


Assuntos
Retinopatia Diabética/diagnóstico , Angiofluoresceinografia/instrumentação , Aumento da Imagem/instrumentação , Processamento de Imagem Assistida por Computador/instrumentação , Disco Óptico , Retina/patologia , Retinopatia Diabética/patologia , Retinopatia Diabética/prevenção & controle , Retinopatia Diabética/cirurgia , Humanos , Fotocoagulação a Laser , Oftalmoscopia , Disco Óptico/patologia , Valores de Referência , Sensibilidade e Especificidade
7.
Ophthalmologe ; 100(12): 1091-7, 2003 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-14704825

RESUMO

BACKGROUND: The assessment of patient's quality of life is not only of vital importance for clinical trials of new therapies but also becomes more and more implemented into daily clinical therapeutical decisions. METHODS: Different methods for evaluating quality of life are available. A well-known questionnaire for measuring global quality of life is the Short Form 36 (SF 36). However, in ophthalmology more specific instruments for measuring visual quality of life are needed. We review the usefulness of specific questionnaires such as the Visual Function 14 (VF-14) or the National Eye Institute Visual Function Questionnaire (NEI-VFQ) in their application to common ophthalmologic diseases such as cataract, age-related macular degeneration and glaucoma. Studies applying these methods were identified by a search in the Medline database. RESULTS: Several instruments to measure visual life quality in ophthalmologic patients are available. Internal consistency and validity are shown. CONCLUSIONS: Evaluating visual quality of life is an important parameter for assessing ophthalmologic diseases and the value of different therapies. It is an important outcome variable in clinical studies. Furthermore, individual visual quality of life should be considered in individual therapeutic decisions and helps to assess the economic effect of current and new therapies.


Assuntos
Oftalmopatias , Oftalmologia , Qualidade de Vida , Inquéritos e Questionários , Visão Ocular , Idoso , Extração de Catarata , Transplante de Córnea , Glaucoma , Humanos , Degeneração Macular , Doenças Retinianas , Acuidade Visual
8.
Ophthalmologe ; 99(5): 384-9, 2002 May.
Artigo em Alemão | MEDLINE | ID: mdl-12043295

RESUMO

BACKGROUND/PURPOSE: Lamellar keratoplasty is an established therapy of corneal pathologies without endothelial involvement and the lack of endothelial rejection is one of the major advantages compared to penetrating keratoplasty. The major disadvantages of manually prepared lamellar corneal grafts are the limited mechanical and optical quality but the automated lamellar therapeutic keratoplasty system ALTK (MORIA) is intended to overcome these disadvantages. The purpose of this preliminary work is to investigate histologically and in clinical cases, if the ALTK system can achieve this aim. PATIENTS AND METHODS: Corneas from two human donors were cut with a 300 microns trephine. After fixation, the stromal bed and the excised cup of one specimen were stained with PAS and examined by light microscopy and the other specimen was analyzed by scanning electron microscopy. In addition, follow-up data of two patients who received such a lamellar graft are reported for the first 9 and 7 months postoperation, respectively. RESULTS: The lamellar cut of homogeneous depth revealed only minor stromal trauma. Both clinical cases demonstrated only minimal interface haze during follow-up. Despite a remarkably clear cornea, visual acuity improved only slowly because the precise lamellar cut tended to partially reproduce any preexisting irregular astigmatism. CONCLUSIONS: The ALTK system simplifies and standardizes the trephination of lamellar corneal grafts but a longer follow up is necessary with respect to visual development and preservation of a clear graft.


Assuntos
Transplante de Córnea/instrumentação , Microcirurgia/instrumentação , Adulto , Criança , Córnea/patologia , Distrofias Hereditárias da Córnea/cirurgia , Topografia da Córnea , Úlcera da Córnea/cirurgia , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Masculino , Microscopia Eletrônica de Varredura , Complicações Pós-Operatórias/patologia , Infecções por Pseudomonas/cirurgia , Doadores de Tecidos
9.
Ophthalmologe ; 98(6): 545-9, 2001 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-11450478

RESUMO

BACKGROUND: The purpose of the study was to determine factors that influence the decision of the next living relative of a deceased for consent on cornea donation. METHODS: The interviews with the relatives of 94 potential cornea donors of the Eye Bank of the Ludwig-Maximilians-Universität, Munich were analysed. The influence of sociological factors on the frequency of obtained consent was investigated. RESULTS: During a 3-month-period, 77 relatives of 94 possible donors were asked for consent to cornea donation and 56 consents (73%) and 21 refusals (27%) were obtained. In 17 (18%) of the cases the relatives could not be reached. Analysis showed a higher consent rate for donors with a university degree (82%) versus those without (71%). Consent was more often obtained for donors who were divorced (88%) than from those who were single (62%). Children of full age (83%) consented more frequently to cornea donation than husbands and wives (78%) or the parents of the deceased (60%). Examination of the postal codes of the residential area indicated more frequent refusals for donors from the rural (54% consent rate) than the urban Munich population (77% consent rate). The situation was the opposite for the residential area of the consenting relative where there was a higher willingness to donate in cases of suicide (93%) in contrast to other causes such as natural deaths (78%) and traffic accidents (71%). CONCLUSION: Socio-economic factors such as education, marital status, residential area and situational factors such as the cause of death, play an important role on the willingness to consent to donate. This study can improve the understanding of the donor family's decision making and as such help the physician asking for consent and improve information to the public which may increase the number of cornea donors in Germany.


Assuntos
Transplante de Córnea , Doadores de Tecidos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Transplante de Córnea/estatística & dados numéricos , Família , Feminino , Alemanha , Humanos , Consentimento Livre e Esclarecido , Tutores Legais , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Doadores de Tecidos/estatística & dados numéricos
10.
Curr Opin Ophthalmol ; 12(2): 94-9, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11224714

RESUMO

The aqueous humor supplies nutrients to the nonvascularized cornea, lens, and trabecular meshwork. A number of tissue growth factors have been detected in this fluid. The composition of these proteins changes dramatically with different ocular conditions, such as inflammation and glaucoma. In this review, an overview of new findings regarding effects of aqueous humor growth factors is given. Our main emphasis is on the regulation of the avascular anterior eye compartment, the possible role of growth factors in the pathogenesis of glaucoma, and the importance of growth factors for the special immunosuppressive status of the anterior chamber.


Assuntos
Humor Aquoso/metabolismo , Substâncias de Crescimento/metabolismo , Homeostase/fisiologia , Animais , Biomarcadores , Córnea/metabolismo , Endoftalmite/imunologia , Endoftalmite/metabolismo , Glaucoma de Ângulo Aberto/imunologia , Glaucoma de Ângulo Aberto/metabolismo , Humanos , Cristalino/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Malha Trabecular/metabolismo
11.
Br J Ophthalmol ; 85(1): 6-10, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11133703

RESUMO

AIMS: To investigate the ultrastructure of the vitreoretinal interface following plasmin induced posterior vitreous detachment. METHODS: Plasmin (1 or 2 U/0.1 ml) was injected into the vitreous cavity of 24 eyes of freshly slaughtered pigs. The 24 fellow eyes received calcium-free and magnesium-free PBS and served as a control. After incubation at 37 degrees C for 30 and 60 minutes, the globes were placed in fixative and hemisected. Specimens for light, scanning, and transmission electron microscopy were obtained from the posterior pole, the equator, and the vitreous base using a corneal trephine. RESULTS: All plasmin treated eyes showed posterior vitreous detachment. However, the inner limiting membrane (ILM) was covered by remnants of cortical vitreous at the posterior pole and at the equator. There was a direct correlation between the concentration and exposure times of plasmin and the degree of vitreoretinal separation. Eyes exposed to 1 U plasmin for 30 minutes had a dense network of residual collagen fibrils while those exposed to 1 U plasmin for 60 minutes had only sparse collagen fibrils covering the ILM. Eyes treated with 2 U plasmin for 60 minutes had a smooth retinal surface, consistent with a bare ILM. At the vitreous base there was no vitreoretinal separation. In all control eyes the vitreous cortex was completely attached to the retina. There was no evidence of retinal damage in any plasmin treated eye. CONCLUSION: Plasmin induces a cleavage between the vitreous cortex and the ILM without morphological changes to the retina. In contrast with previous reports, plasmin produces a smooth retinal surface and additional surgery is not required in this experimental setting. The degree of vitreoretinal separation depends on the concentration and length of exposure to plasmin.


Assuntos
Fibrinolisina/farmacologia , Fibrinolíticos/farmacologia , Retina/efeitos dos fármacos , Vitrectomia/métodos , Corpo Vítreo/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Microscopia Eletrônica , Microscopia Eletrônica de Varredura , Técnicas de Cultura de Órgãos , Retina/ultraestrutura , Suínos , Fatores de Tempo , Corpo Vítreo/ultraestrutura
12.
Curr Eye Res ; 21(1): 588-94, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11035541

RESUMO

PURPOSE: To investigate alphaB-Crystallin expression and localization in the lacrimal gland and tear fluid. METHODS: Mouse, rat, porcine, monkey and human lacrimal gland samples were immuno-histochemically and immuno-electron-microscopically stained with various antibodies against alphaB-crystallin. Western- and Northern-blotting was performed to demonstrate the presence of alphaB-crystallin mRNA and protein. Human tear fluid was analyzed for the presence of alphaB-crystallin using dot blotting. RESULTS: alphaB-Crystallin is located in the lacrimal gland duct cells but not in the acini. Electron microscopically, the protein was frequently found in apical electron-dense granules of lacrimal duct cells, occasionally also in the duct lumina. Western blotting confirmed the presence of alphaB-crystallin in the lacrimal gland, Northern blot samples revealed the presence of alphaB-crystallin mRNA. In the human tear fluid, alphaB-crystallin was present in all samples investigated. CONCLUSIONS: We demonstrate for the first time that alphaB-crystallin is present in the lacrimal gland. Presence of the protein in apical secretory granules as well as presence in the tear fluid might indicate secretion of alphaB-crystallin into the tear fluid.


Assuntos
Cristalinas/metabolismo , Aparelho Lacrimal/metabolismo , Lágrimas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Northern Blotting , Western Blotting , Humanos , Imuno-Histoquímica , Aparelho Lacrimal/citologia , Aparelho Lacrimal/ultraestrutura , Macaca , Camundongos , Microscopia Imunoeletrônica , Pessoa de Meia-Idade , Ratos , Suínos , Distribuição Tecidual
13.
Invest Ophthalmol Vis Sci ; 41(8): 2229-38, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10892867

RESUMO

PURPOSE: To study whether human trabecular meshwork (HTM) cells are capable of expressing and secreting tissue transglutaminase (tTgase), an enzyme cross-linking extracellular matrix (ECM) proteins, and whether tTgase and synthesis of cross-linked fibronectin are increased after treatment of HTM cells with transforming growth factor (TGF)-beta1 or -beta2. METHODS: Anterior segments of six normal human eyes were stained with antibodies to tTgase. Tissues from three eyes were analyzed for tTgase using Western blot analysis. Monolayer cultures of HTM cells from eyes of five human donors were treated with 1.0 ng/ml TGF-beta1, -beta2, or 5 X 10(-7) M dexamethasone (DEX) for 12 to 96 hours. Induction of tTgase was investigated by Western and Northern blot analysis. External tTgase activity was measured by the ability to form polymerized fibronectin and the incorporation of biotinylated cadaverine into fibronectin. RESULTS: Labeling for tTgase was observed throughout the entire HTM. Cultured HTM cells expressed tTgase intra- and extracellularly. Treatment of cultured HTM cells with TGF-beta1 and -beta2 increased the tTgase mRNA and protein levels, whereas DEX had no effect. TGF-beta-treated HTM cells showed a significant increase in polymerized and unpolymerized fibronectin. Incorporation of biotinylated cadaverine was markedly increased when HTM cells were treated with TGF-beta for 24 hours before seeding. CONCLUSIONS: The enzyme tTgase is expressed in the HTM and is inducible by TGF-beta1 or -beta2 in cultured HTM cells. Extracellular tTgase is able to polymerize fibronectin. Increased levels of TGF-beta2 in the aqueous humor may lead to an increase of tTgase expression and activity in the HTM, causing an increase of irreversibly cross-linked ECM proteins. This mechanism might play a role for the increased outflow resistance seen in glaucomatous eyes.


Assuntos
Malha Trabecular/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Transglutaminases/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Cadaverina/metabolismo , Células Cultivadas , Criança , Dexametasona/farmacologia , Indução Enzimática/efeitos dos fármacos , Fibronectinas/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Glucocorticoides/farmacologia , Humanos , Pessoa de Meia-Idade , RNA Mensageiro/biossíntese , Malha Trabecular/enzimologia , Transglutaminases/genética
14.
Graefes Arch Clin Exp Ophthalmol ; 238(12): 993-7, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11196363

RESUMO

BACKGROUND: In a recent study we showed that, in vitro, transforming growth factor-beta 2 (TGF-beta 2) induces alpha B-crystallin expression in cultured trabecular meshwork (TM) cells, but not in cultured fibroblasts. We assumed that alpha B-crystallin can be induced by TGF-beta 2 only if the cells are already expressing a basal level of the protein. In the present study we therefore treated cultured ciliary muscle (CM) cells constitutively expressing alpha B-crystallin and investigated the effect of TGF-beta on expression of alpha B-crystallin and the corresponding mRNA in these cells. MATERIAL AND METHODS: Monolayer cultures of third-passage CM cells from eyes of five human donors (12-73 years), being confluent for 7 days, were treated with 1.0 ng/ml TGF-beta 1 or TGF-beta 2. Induction of alpha B-crystallin and the related mRNA was investigated by immunofluorescence and by western and northern blot analysis. RESULTS: An increase in alpha B-crystallin mRNA was observed following treatment with TGF-beta. Actinomycin blocked the induction of alpha B-crystallin by the cytokine TGF-beta. Using western blotting the increase in alpha B-crystallin expression in CM cells was only small. CONCLUSION: These results confirm our assumption that induction of alpha B-crystallin by the cytokine TGF-beta depends on basal levels of the protein and its mRNA constitutively present within the cells. Comparison of the increase in alpha B-crystallin mRNA and protein expression indicate that post-transcriptional regulation mechanisms are responsible for these findings in CM cells.


Assuntos
Corpo Ciliar/efeitos dos fármacos , Cristalinas/biossíntese , Músculo Liso/efeitos dos fármacos , RNA Mensageiro/biossíntese , Fator de Crescimento Transformador beta/farmacologia , Idoso , Western Blotting , Células Cultivadas , Criança , Corpo Ciliar/citologia , Corpo Ciliar/metabolismo , Cristalinas/genética , Técnica Indireta de Fluorescência para Anticorpo , Expressão Gênica , Humanos , Pessoa de Meia-Idade , Músculo Liso/citologia , Músculo Liso/metabolismo , Fator de Crescimento Transformador beta1 , Fator de Crescimento Transformador beta2
15.
Invest Ophthalmol Vis Sci ; 40(13): 3209-14, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10586944

RESUMO

PURPOSE: To determine whether the capacity to induce ACAID by antigen injection into the anterior chamber is altered in animals with genetically determined retinal degeneration and increased age. METHODS: Anterior chamber-associated immune deviation (ACAID) induced by injection of ovalbumin into the anterior chamber of the eye was studied in three rodent strains with different forms of hereditary retinal degeneration (Royal College of Surgeon [RCS] rats, retinal degeneration [rd] mice, and Norrie-Disease [ND] mice) and in different age groups (age range, 1-23 months). The data were compared with those of age-matched controls. Aqueous humors of rd mice, RCS rats, and age-matched congenic controls were investigated for concentrations of transforming growth factor-beta2 (TGF-beta2) using enzyme-linked immunosorbent assay. RESULTS: ACAID was readily induced in RCS rats and ND mice irrespective of amount of retinal degeneration or aging. In rd mice ACAID could be induced in young animals but not in animals more than 12 months of age. In old rd mice, loss of ACAID was accompanied by a marked reduction in total TGF-beta2 levels in aqueous humor. CONCLUSIONS: Rd mice more than 1 year of age lose the capacity of the anterior chamber to support the induction of ACAID by intracameral injection of soluble protein antigen. Because loss of ACAID correlated with a decrease in TGF-beta2 concentration in aqueous humor, it is proposed that eyes of rd mice are unable to maintain an immunosuppressive microenvironment necessary for ACAID.


Assuntos
Envelhecimento/imunologia , Câmara Anterior/imunologia , Oftalmopatias Hereditárias/imunologia , Degeneração Retiniana/imunologia , Animais , Câmara Anterior/metabolismo , Humor Aquoso/metabolismo , Ensaio de Imunoadsorção Enzimática , Oftalmopatias Hereditárias/genética , Oftalmopatias Hereditárias/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Ovalbumina/imunologia , Ratos , Ratos Mutantes , Degeneração Retiniana/genética , Degeneração Retiniana/metabolismo , Fator de Crescimento Transformador beta/metabolismo
16.
Invest Ophthalmol Vis Sci ; 40(10): 2235-41, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10476788

RESUMO

PURPOSE: Because in glaucomatous eyes transforming growth factor-beta (TGF-beta) and alphaB-crystallin are increased in the anterior eye segment, the effect of TGF-beta1 and TGF-beta2 on the expression of alphaB-crystallin and its corresponding mRNA was studied in human trabecular meshwork (TM) cells. METHODS: Monolayer cultures of "cribriform" and "corneoscleral" TM cells of 5 human donors (12-73 years of age) were treated with either 1.0 ng/ml TGF-beta1, TGF-alpha2, or 5 X 10(-7) dexamethasone (DEX) for 12 to 96 hours. Induction of alphaB-crystallin and the related mRNA was investigated by western and northern blot analyses. For comparison, human foreskin fibroblasts (HFF) and NIH 3T3 cells were treated in the same way as the TM cells. RESULTS: An increase of alphaB-crystallin mRNA was observed after treatment of TM cells with TGF-beta1 and TGF-beta2, whereas DEX had no effect. In the cribriform TM cells with a high basal level, the enhancement ranged between 2 and 3 times; whereas in the corneoscleral TM cells alphaB-crystallin mRNA increased between 5 and 6 times. Using western blot analysis, the increase of alphaB-crystallin expression in the cribriform TM cells was only small compared with the significant increase in the corneoscleral TM cells. Treatment of HFF and NIH 3T3 cells with TGF-beta did not induce alphaB-crystallin mRNA. CONCLUSIONS: This is the first time to show that alphaB-crystallin is not only induced by stress factors but also by TGF-beta in TM cell cultures. The difference in induction of mRNA and protein seems to be dependent on alphaB-crystallin concentration before treatment.


Assuntos
Cristalinas/biossíntese , Malha Trabecular/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Idoso , Animais , Northern Blotting , Western Blotting , Células Cultivadas , Criança , Cristalinas/genética , Dexametasona/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Macaca fascicularis , Camundongos , Microscopia Imunoeletrônica , Pessoa de Meia-Idade , RNA Mensageiro/biossíntese , Malha Trabecular/metabolismo , Malha Trabecular/ultraestrutura
17.
Invest Ophthalmol Vis Sci ; 39(12): 2450-7, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9804153

RESUMO

PURPOSE: To correlate morphologic changes in the retinal vasculature with degenerative changes in the neuronal retina of mice lacking 56 amino acids from the N-terminus of the Norrie disease (ND) gene product. METHODS: Posterior eye segments of ND mice of different age groups were investigated by light and electron microscopy (EM) and scanning EM of vascular corrosion cast preparations. The results were qualitatively and quantitatively compared with those obtained in age-matched littermate control mice and C57B1/6 mice. RESULTS: Quantitative evaluation revealed an increase in the number of blood vessels in the interface of the ganglion cell layer and the nerve fiber layer and a decrease in the inner and outer plexiform layers in ND mice older than 9 days compared with control mice. Vessels were also seen adjacent to the vitreous surface of the inner limiting membrane. Most of these vessels showed fenestrations and occasionally penetrated the inner limiting membrane. Hyaloid vessels were still present in the vitreous. The abnormal vascularization pattern was found in the entire retina and occurred in addition to the previously described alterations of the neuronal retina. CONCLUSIONS: There is a malformation of the retinal vasculature and a persistence of hyaloid vessels in the vitreous of ND mice. It is assumed that the ND gene product is required for normal vascularization of the inner retinal layers and for atrophy of hyaloid vessels.


Assuntos
Cegueira/genética , Cegueira/patologia , Degeneração Retiniana/genética , Degeneração Retiniana/patologia , Vasos Retinianos/patologia , Animais , Molde por Corrosão , Proteínas do Olho/genética , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura , Proteínas do Tecido Nervoso/genética , Vasos Retinianos/ultraestrutura
18.
Artigo em Inglês | MEDLINE | ID: mdl-9579354

RESUMO

To study the distribution of alpha B-crystallin, formalin-fixed preparations of the inner ear of the rat, cynomolgus monkey, rhesus monkey and human were stained immunohistochemically for alpha B-crystallin. In all cochleae investigated, intense staining for alpha B-crystallin was found in the inner and outer pillars as well as in the cells of Hensen and Claudius. In the primate inner ear, alpha B-crystallin was also present in the polygonal epithelial cells of Reissner's membrane, the interdental cells and some fibrocytes of the spiral limbus, epithelial cells of the outer spiral sulcus and the Schwann cells of the 8th nerve. In the primate stria vascularis, alpha B-crystallin was mainly seen in the basal cell layer and the adjacent cells of the connective tissue layer. alpha B-crystallin was found to be present in a large variety of cells in the inner ear surrounding the scala media.


Assuntos
Cristalinas/metabolismo , Orelha Interna/metabolismo , Proteínas de Choque Térmico/metabolismo , Chaperonas Moleculares/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Humanos , Imuno-Histoquímica , Macaca fascicularis , Macaca mulatta , Ratos , Ratos Wistar
19.
Eur J Cell Biol ; 75(1): 78-84, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9523158

RESUMO

Aqueous humor outflow in primate eyes can be facilitated by ciliary muscle contraction, thereby widening fluid pathways through the trabecular meshwork. Recently in the scleral spur smooth muscle (sm) alpha-actin positive myofibroblast-like cells have been described which are in contact with the elastic fiber system of both the spur and trabecular meshwork. In the vicinity of these cells nerve terminals have been described. It is speculated that contraction of scleral spur cells can facilitate aqueous humor outflow, too. To provide a tool for further physiological and pharmacological studies monolayer cell cultures of human scleral spur have been established and characterized. For this purpose, cells derived from scleral spur, outer and inner trabecular meshwork and ciliary muscle tips from 7 donor eyes (43-87 years-old respectively, obtained 3-7 h post mortem) were grown in tissue culture medium and the different monolayer cells classified by their growth characteristics, and by immunohistochemical staining for vimentin, alpha-sm-actin, desmin, and alpha B-crystallin, respectively. In addition, the presence of alpha B-crystallin mRNA and desmin mRNA was verified using the polymerase chain reaction (PCR)-method. We were able to characterize and distinguish human scleral spur cells from adjacent ciliary muscle and trabecular meshwork cells. Scleral spur cells (SPC) grew slower than ciliary muscle cells (CMC) but much faster than trabecular meshwork cells (TMC). All cells showed the same staining characteristics in vitro as they did in vivo. Scleral spur cells stained for vimentin and alpha-sm-actin, but not for desmin and alpha B-crystallin. The corresponding mRNAs of the latter two proteins could not be detected by PCR in the spur cells. Cells grew out from all donor eyes so that they actually provide a tool for further experimental studies.


Assuntos
Esclera/citologia , Esclera/crescimento & desenvolvimento , Técnicas de Cultura de Células , Divisão Celular , Separação Celular/métodos , Células Cultivadas , Humanos , Imuno-Histoquímica , Músculos Oculomotores/citologia , Reação em Cadeia da Polimerase , Esclera/química , Malha Trabecular/citologia
20.
J Comput Assist Tomogr ; 21(3): 447-51, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9135656

RESUMO

PURPOSE: Imaging of eye movement disorders has so far been restricted to the semifunctional cine mode of CT and MRI. Since real-time imaging of eye movement is necessary to investigate dynamic disorders, the aim of our study was to implement a fast MR technique to investigate eye movement in a real-time mode. METHOD: Six healthy volunteers and three patients suffering from end-point nystagmus were examined with fast MR sequences while performing the following eye movements: holding different gaze positions, reading a defined text to demonstrate saccadic movements, and holding a primary gaze position and maximal end-point position to cause nystagmus when present. RESULTS: In all cases, we were able to delineate eye movement with fast MRI. Anatomic and functional information could be obtained simultaneously for the first time through observation of saccadic and pursuit eye movements. CONCLUSION: Fast MRI allows for the assessment of dynamic eye movement without the restrictions of cine mode and is able to provide the clinician with additional information in the evaluation of functional movement disorders.


Assuntos
Movimentos Oculares , Imageamento por Ressonância Magnética/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nistagmo Patológico/diagnóstico , Nistagmo Patológico/fisiopatologia
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