RESUMO
BACKGROUND: Light-induced oxidative stress is an suggested reason for retinal pigment epithelium (RPE) degeneration in age-related macular degeneration (AMD). This study investigates the influence of light on intracellular reactive oxygen species (ROS) and apoptosis in the human RPE and potential cytoprotective effects of the tetracycline antibiotic minocycline. METHODS: Primary human RPE cells were either pre- or post-incubated with minocycline and then exposed to white light or oxidative stress (600 µM, H(2)O(2)). Then viability, induction of intracellular reactive oxygen species (ROS), apoptosis and cell death was determined. Expression of apoptotic BAX and anti-apoptotic Bcl-2 protein and their mRNA were determined by RT-PCR and Western blot analysis. RESULTS: Both light exposure and oxidative stress decreased RPE cell viability and Bcl-2 expression and increased intracellular ROS, apoptotic cell death, and BAX expression. Minocycline reduced these effects under certain conditions. CONCLUSIONS: This study demonstrates that minocycline effectively protects human RPE cells against oxidative damage. However, in the light of minocycline's photosensitising properties its potential role in AMD treatment needs further evaluation.
Assuntos
Antibacterianos/uso terapêutico , Citoproteção/efeitos dos fármacos , Degeneração Macular/tratamento farmacológico , Degeneração Macular/fisiopatologia , Minociclina/uso terapêutico , Antibacterianos/efeitos adversos , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Western Blotting , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Proliferação de Células , Células Cultivadas/efeitos dos fármacos , Humanos , Luz/efeitos adversos , Degeneração Macular/diagnóstico , Degeneração Macular/genética , Minociclina/efeitos adversos , Epitélio Pigmentado Ocular/efeitos dos fármacos , Epitélio Pigmentado Ocular/fisiopatologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína X Associada a bcl-2/genéticaRESUMO
OBJECTIVES: Growth factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and placenta growth factor (PlGF) are key players in the development of diabetic retinopathy, age-related macular degeneration, and other retinal neovascular diseases. Glial cells provide a significant source of retinal growth factor production under physiologic and pathologic conditions. Cumulative light exposure has been linked to increased retinal growth factor expression. Previous reports indicate that sorafenib, an oral multikinase inhibitor, might have a beneficial effect on retinal neovascularization. This study was designed to investigate the effects of sorafenib on light-induced overexpression of growth factors in human retinal glial cells. METHODS: Primary human optic nerve head astrocytes (ONHAs) were exposed to white light and incubated with sorafenib. Viability, expression, and secretion of VEGF-A, PDGF-BB, and PlGF and their mRNA were determined by reverse transcription-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. RESULTS: Light exposure decreased cell viability and increased VEGF-A, PDGF-BB, and PlGF expression and secretion. These light-induced effects were significantly reduced when cells were treated with sorafenib at a concentration of 1 microg/ml. CONCLUSION: Sorafenib significantly reduced light-induced overexpression of VEGF-A, PDGF-BB, and PlGF in primary human ONHAs. Sorafenib has promising properties as a potential supportive treatment for retinal neovascularization.
Assuntos
Benzenossulfonatos/farmacologia , Disco Óptico/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Proteínas da Gravidez/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Retina/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto , Idoso , Astrócitos/efeitos dos fármacos , Astrócitos/efeitos da radiação , Benzenossulfonatos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Humanos , Luz/efeitos adversos , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Disco Óptico/imunologia , Disco Óptico/metabolismo , Disco Óptico/efeitos da radiação , Compostos de Fenilureia , Fator de Crescimento Placentário , Fator de Crescimento Derivado de Plaquetas/biossíntese , Proteínas da Gravidez/biossíntese , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Retina/metabolismo , Retina/efeitos da radiação , Neovascularização Retiniana/tratamento farmacológico , Sorafenibe , Fator A de Crescimento do Endotélio Vascular/biossínteseRESUMO
BACKGROUND: The aim of this study was to investigate the clinical long-term outcome of the 1CU posterior chamber IOL. Objective accommodative dynamics as well as measured data were assessed subjectively three months and 72 months after implantation. PATIENTS AND METHODS: Retrospectively, 26 eyes after uneventful cataract surgery with 1CU IOL implantation were included. In 26 eyes (group I), the change of the anterior IOL reflex without and under stimulation with pilocarpine 1 %, and cyclopentolate (pseudophakic-accommodation), and maximum obfuscation under best corrected visual acuity (BCVA) settings (pseudo-accommodation) were examined. In 20 eyes (group II) the influence of the laser capsulotomy on the pseudophakic-accommodation was evaluated. RESULTS: Eyes, stimulated by pilocarpine 1 %, have an anterior (-) shift of the IOL reflex of -0.59 +/- 0.28 mm (pseudophakic-accommodation) after 3 months and -0.49 +/- 0.27 mm after 50.8 months (p < 0.001). The mean obfuscation under BCVA level (pseudo-accommodation) was 1.5 diopters (D). Laser capsulotomy was performed after 21 +/- 15 months in the mean. A change of the anterior reflex of the IOL of -0.5 +/- 0.3 mm before and after Nd:YAG laser treatment did not show any statistical significance. CONCLUSIONS: Under application of pilocarpine 1 % and cyclopentolate a small movement of the 1CU-IOL was examined. The amount of the anterior/posterior shift of the IOL reflex was stable over the follow-up period but is not sufficient to provide full presbyopic correction.
Assuntos
Doenças do Cristalino/cirurgia , Implante de Lente Intraocular/métodos , Lentes Intraoculares , Adulto , Idoso , Feminino , Humanos , Doenças do Cristalino/diagnóstico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
PURPOSE: Although several screening methods exist, postoperative corneal ectasia after refractive surgery is a severe complication. One possibility for this might be the fact that screening methods may fail in detection of preoperative risk factors such as forme fruste keratoconus (FFKC). METHODS: Retrospective evaluation of four cases that showed only mild changes of FFKC on placido-based topography but revealed indicative findings on Scheimpflug imaging (Pentacam). RESULTS: While in placido-based topography evaluation of corneal topography did not show a clear FFKC, the evaluation of corneal topography on Scheimpflug imaging together with the data of spatial corneal thickness revealed distinctive FFKC in all cases presented. CONCLUSIONS: Although both methods bear the risk of not detecting pre-existing FFKC, Scheimpflug imaging seems superior to placido-based corneal topography alone.
Assuntos
Córnea/patologia , Topografia da Córnea/métodos , Ceratocone/diagnóstico , Fotografação/métodos , Adulto , Astigmatismo/diagnóstico , Dilatação Patológica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Estudos RetrospectivosRESUMO
PURPOSE: Comparison of the central corneal refractive power before and after myopic LASIK using the Keratograph and the Pentacam. The Scheimpflug technique (Pentacam) enables the measurement of the corneal refractive power by examining the anterior and posterior corneal curvature. METHOD: The corneal refractive power of 59 eyes was examined before, 3 months and 6 months after myopic LASIK. The refractive power was measured at the corneal apex and at a distance of 2 and 4 mm. Statistical analysis was performed using the Wilcoxon signed rank test; a p value of 0.05 or less was considered statistically significant. RESULTS: At the corneal apex and at a distance of 2 mm the findings with the Keratograph showed a higher refractive power of up to 1.05 D. The differences were statistically significant at all times. At a distance of 4 mm from the corneal apex postoperatively there was no statistically significant difference. CONCLUSION: The results using the Pentacam system showed a lower corneal refractive power following myopic LASIK at all times. Its measuring principle compared to that of the Keratograph should be preferred when detecting changes of the refractive power of the central cornea after corneal refractive procedures.
Assuntos
Ceratomileuse Assistida por Excimer Laser In Situ , Miopia/diagnóstico , Miopia/cirurgia , Erros de Refração/diagnóstico , Refratometria/instrumentação , Adulto , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miopia/complicações , Erros de Refração/etiologia , Refratometria/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
BACKGROUND: Not only medical care and prescription of magnifying devices, but also social and professional rehabilitation are part of a complete interdisciplinary low vision service. This study provides quantitative data about the success of rehabilitation and the quality of the Low Vision Department's work. PATIENTS AND METHODS: A sample of 105 visually disabled patients, who had already been provided with magnifying aids and other rehabilitation measures by the Low Vision Department, answered a questionnaire about quality control during a follow-up visit. The survey was carried out between May and October 2004. Patients were asked to rate the different rehabilitation measures and to comment on how frequently they used the different magnifying devices. Furthermore, they were asked to judge to what degree they coped with different life situations when using or not using the low vision aids. RESULTS: The most frequently used aids were magnifiers (61%), glasses for near vision (34%), closed circuit television (20%), and monocular telescopes (20%). Of the 105 patients, 85 (81%) reported on frequent use of the devices, with just 3 patients (3%) reporting that they hardly ever used the aids. Only 2% of the patients could read newspaper text without the use of magnifying aids, while 51% were able to do this using the aids; 46% of the patients reported that they had profited from the social and professional rehabilitation measures. CONCLUSION: Independently from the causal ophthalmologic diagnosis, patients were found to have benefited greatly from the rehabilitation measures provided by the Low Vision Department, enabling them to take part in more activities and participate more fully in social life, thereby greatly improving their quality of life. Frequent use of the low vision aids by the patient was ensured when offered alongside continued professional support.
Assuntos
Cegueira/reabilitação , Óculos/normas , Leitura , Reabilitação Vocacional , Auxiliares Sensoriais/normas , Baixa Visão/reabilitação , Idoso , Idoso de 80 Anos ou mais , Cegueira/diagnóstico , Cegueira/etiologia , Cegueira/psicologia , Feminino , Humanos , Masculino , Miopia/diagnóstico , Miopia/etiologia , Miopia/psicologia , Miopia/reabilitação , Satisfação do Paciente , Controle de Qualidade , Qualidade de Vida/psicologia , Inquéritos e Questionários , Baixa Visão/diagnóstico , Baixa Visão/etiologia , Baixa Visão/psicologiaRESUMO
BACKGROUND: Vitreoretinal adhesions play a crucial role in the development of a macular hole. To visualize vitreoretinal adhesion we used optical coherence tomography to investigate fellow eyes of patients with macular holes. METHODS: In a prospective study we scanned the retina in 188 patients with a macular hole stage III or IV (Gass classification). The foveal shape and vitreous were classified into grades. RESULTS: Of the 188 patients 45% showed no vitreous reflex, 45% a partial vitreous detachment with foveolar adhesions, and 10% a vitreous detachment with complete separation from the fovea. While eyes with normal foveolar shape displayed partial vitreous detachment in 33%, this figure rose to 66% in eyes with a macular hole stage I. CONCLUSION: Diffuse thickening of the fovea is followed by an intraretinal split and formation of a cyst. The shape of the foveolar adhesion suggests that continuing anteroposterior vitreal traction leads to a retinal break and formation of a full-thickness macular hole.
Assuntos
Retina/patologia , Perfurações Retinianas/diagnóstico , Tomografia , Corpo Vítreo/patologia , Idoso , Feminino , Fóvea Central/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Aderências Teciduais , Descolamento do Vítreo/diagnósticoRESUMO
BACKGROUND: Cumulative light exposure is significantly associated with progression of age-related macular degeneration (AMD). Inhibition of vascular endothelial growth factor A (VEGF) is the main target of current antiangiogenic treatment strategies for AMD. Previous reports indicated that sorafenib, an oral multikinase inhibitor, might have beneficial effects on exudative AMD. This study investigates the effects of sorafenib on light-induced overexpression of VEGF and its receptors VEGFR1 and 2 in human retinal pigment epithelial (RPE) cells. METHODS: The effects of sorafenib on VEGFR1 and 2 expression of primary human RPE cells was investigated by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and western blotting. In addition, RPE cells were exposed to white light and incubated with sorafenib. Viability, expression of VEGF and its mRNA were determined by RT-PCR, immunohistochemistry, western blotting, and enzyme-linked immunosorbent assays. RESULTS: Sorafenib reduced VEGFR1 and 2 expression of RPE cells. Light exposure decreased cell viability and increased expression and secretion of VEGF. These light-induced effects were significantly reduced when cells were treated with sorafenib at a dose of 1 µg/ml. CONCLUSION: The results show that sorafenib has promising properties as a potential antiangiogenic treatment for AMD.
Assuntos
Benzenossulfonatos/farmacologia , Piridinas/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto , Inibidores da Angiogênese/farmacologia , Citoproteção/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Inibidores de Proteínas Quinases/farmacologia , Sorafenibe , Resultado do Tratamento , Adulto JovemRESUMO
METHODS: Primary human RPE cells were exposed to white light and either a SN60AT or SA60AT IOL was placed in the light beam. After 15-60 min of irradiation, viability, induction of apoptosis and cell death were determined in primary human RPE cells. Expression of vascular endothelial growth factor A (VEGF-A) and the anti-apoptotic XIAP protein and their mRNA were determined by RT-PCR, Western blot analysis and ELISA. RESULTS: Light exposure decreased cell viability depending on the duration of irradiation. Light-induced cell death and apoptosis as well as decrease of XIAP expression and cellular viability were significantly reduced by both the SN60AT and SA60AT IOL. In addition, these protective effects regarding light-induced cell damage were significantly stronger in the presence of the blue light-filtering SN60AT IOL compared to the SA60AT IOL. CONCLUSION: Both UV-filtering and blue light-absorbing IOLs reduce light-induced RPE damage. The blue light-absorbing IOL further reduced damage compared to the conventional IOL, which supports the hypothesis of possibly also preventing retinal damage in clinical use.
Assuntos
Filtração/instrumentação , Lentes Intraoculares , Luz/efeitos adversos , Epitélio Pigmentado Ocular/efeitos da radiação , Desenho de Prótese , Proteção Radiológica/instrumentação , Raios Ultravioleta/efeitos adversos , Apoptose/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Ensaio de Imunoadsorção Enzimática , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Técnicas In Vitro , Degeneração Macular/etiologia , Degeneração Macular/prevenção & controle , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator A de Crescimento do Endotélio Vascular/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genéticaRESUMO
Current studies emphasize the use of array coils to decrease noise and increase the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). We applied T1-weighted and T2-weighted standard nonbreathhold spin echo (SE) sequences and T1-weighted FLASH, TurboFLASH, T2-weighted spin-echo time (TSE), and heavily T2-weighted half Fourier acquisition single-shot TSE (HASTE) sequences during breathhold for abdominal imaging in 15 normal volunteers. The breathhold scans were performed using both a standard coil and a circular polarized array coil. We analyzed the signal intensity (SI), SNR, and CNR of abdominal organs in all sequences. SNRs increased in all cases by an overall factor of approximately 3 due to an 8% increase in overall SIs and a 50% decrease in noise when applying the array coil. Although the array-coil FLASH sequence performed at least as well as the respective SE sequence, the SNRs of the array-coil TurboFLASH, TSE breathhold, and HASTE sequences were generally lower. We conclude that array-coil imaging significantly improves fast imaging of the abdomen.
Assuntos
Abdome/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Respiração/fisiologia , Abdome/fisiologia , Adulto , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/instrumentaçãoRESUMO
PURPOSE: To determine the efficacy of fast MRI techniques using a tailored imaging design (breathhold and array-surface coil), conventional T1-, T2-weighted spin-echo (SE) sequences and breathhold gradient-echo (GRE) T1- and breathhold fast SE T2-weighted images were compared. METHODS: 20 patients with proven focal liver lesions were studied on a 1.5 Tesla system. Conventional SE T1- and T2-weighted imaging, as well as GRE T1- and fast SE T2-weighted imaging was performed. Fast imaging was done during breathhold using an array-surface coil. For all sequences signal-to-noise ratios (S/N) and liver-to-lesion-contrast ratios (L/L) were measured and statistically compared. In addition, two blinded readers qualitatively evaluated all images, using a score system regarding artifacts (breathing, pulsation), number of lesions, and over-all image quality. RESULTS: Regarding image quality parameters, S/N and L/L, there was no significant (p > 0.05) difference between the conventional and fast imaging techniques. However, GRE imaging was superior (84.8%) to conventional imaging for breathing and pulsation artifacts, while fast SE T2 imaging was equal regarding breathing artifacts, but superior (51.5%) regarding pulsation artifacts. The number of detected hepatic lesions was identical in all sequences. CONCLUSION: The fast MRI techniques demonstrated a superiority to conventional imaging regarding image quality and presence of artifacts. Therefore, fast imaging techniques can replace conventional techniques, at least in patients that can sufficiently sustain breathing.