RESUMO
BACKGROUND AND OBJECTIVE: To present a case series to elucidate a novel technique that involves the creation of an arcuate retinotomy in the treatment of large macular holes after failed primary repair. PATIENTS AND METHODS: retrospective chart review. Six eyes (six patients) with large macular holes, all of which had failed primary repair, underwent 25 gauge pars plana vitrectomy revision coupled with full thickness arcuate retinotomy temporal to the macular hole and fluid-gas exchange. The main outcome measure was anatomic macular hole closure based on optical coherence tomography (OCT), with visual acuity and visual field evaluation as secondary outcome measures. RESULTS: Five of the six patients (83%) had successful hole closure with three of the six patients (50%) exhibiting improvement in visual acuity. CONCLUSION: Arcuate retinotomy is a new approach that may aide in the repair of large macular holes not otherwise amenable to closure with traditional techniques.
Assuntos
Procedimentos Cirúrgicos Oftalmológicos , Retina/cirurgia , Perfurações Retinianas/cirurgia , Tamponamento Interno , Feminino , Fluorocarbonos/administração & dosagem , Seguimentos , Humanos , Masculino , Decúbito Ventral , Reoperação , Estudos Retrospectivos , Hexafluoreto de Enxofre/administração & dosagem , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Campos Visuais/fisiologia , VitrectomiaRESUMO
PURPOSE: To evaluate the effect of bevacizumab on the mitochondrial function of human retinal pigment epithelial (ARPE-19), rat neurosensory retinal (R28) and human microvascular endothelial (HMVEC) cells in culture. MATERIALS AND METHODS: ARPE-19 and R28 cells were treated with 0.125, 0.25, 0.50 and 1 mg/ml of bevacizumab. The HMVEC cultures were treated with 0.125, 0.25, 0.50 and 1 mg/ml of bevacizumab or 1 mg/ml of immunoglobulin G (control). Mitochondrial function assessed by mitochondrial dehydrogenase activity (MDA) was determined using the WST-1 assay. RESULTS: Bevacizumab doses of 0.125 to 1 mg/ml for 5 days did not significantly affect the MDA of ARPE-19 cells. Bevacizumab treatment at 0.125 and 0.25 mg/ml (clinical dose) did not significantly affect the MDA of R28 cells; however, 0.50 and 1 mg/ml doses significantly reduced the R28 cell mitochondrial function. All doses of bevacizumab significantly reduced the MDA of proliferating and non-proliferating HMVEC. CONCLUSION: Bevacizumab exposure for 5 days was safe at clinical doses in both ARPE-19 and R28 retinal neurosensory cells in culture. By contrast, bevacizumab exposure at all doses show a significant dose-dependent decrease in mitochondrial activity in both the proliferating and non-proliferating HMVEC in vitro. This suggests a selective action of bevacizumab on endothelial cells at clinical doses.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Endotélio Vascular/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Vasos Retinianos/ultraestrutura , Inibidores da Angiogênese/farmacologia , Animais , Animais Recém-Nascidos , Bevacizumab , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Endotélio Vascular/ultraestrutura , Humanos , Degeneração Macular/tratamento farmacológico , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Microscopia de Contraste de Fase , Células Fotorreceptoras de Vertebrados/diagnóstico por imagem , Células Fotorreceptoras de Vertebrados/metabolismo , Ratos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/ultraestrutura , Vasos Retinianos/efeitos dos fármacos , Vasos Retinianos/metabolismo , Ultrassonografia , Fator A de Crescimento do Endotélio VascularRESUMO
OBJECTIVES: To determine whether expression of thrombospondin-1 (TSP1), an endogenous inhibitor of angiogenesis, is downregulated during progression of uveal melanoma and whether administration of TSP1 and/or its antiangiogenic peptides attenuate tumor growth. METHODS: Tyrosinase-SV40 T-antigens (Tyr Tag) transgenic mice were used for evaluation of TSP1 expression during tumor progression using immunohistological methods. The therapeutic potential of TSP1 on tumor progression was evaluated either by crossing Tyr Tag mice with a line of transgenic mice overexpressing TSP1 in the eye or by administration of TSP1-mimetic peptide with known antiangiogenic, antitumor activity. Tumor areas were measured in histological sections using Optima software (Media Cybernetics, Inc). RESULTS: The Tyr Tag tumors from 3-week-old mice showed significant TSP1 expression, which was dramatically downregulated in tumors from 12-week-old mice. Furthermore, the development and progression of tumor was significantly delayed in Tyr Tag TSP1 transgenic mice or Tyr Tag mice receiving TSP1-mimetic peptide (100 mg/kg/d). CONCLUSIONS: Expression of TSP1 was decreased with the angiogenic switch during progression of uveal melanoma, and TSP1 and/or its antiangiogenic peptides were effective in attenuation of tumor growth. CLINICAL RELEVANCE: Modulation of TSP1 expression and/or activity may be beneficial in treating uveal melanoma.
Assuntos
Melanoma/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Trombospondina 1/genética , Trombospondina 1/farmacologia , Neoplasias Uveais/tratamento farmacológico , Animais , Modelos Animais de Doenças , Progressão da Doença , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Melanoma/irrigação sanguínea , Melanoma/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neovascularização Patológica/genética , Peptídeos/farmacologia , Neoplasias Uveais/irrigação sanguínea , Neoplasias Uveais/genéticaRESUMO
A 76-year-old man presented atypically with a 4-week history of a rapidly enlarging ulcerated nodular lesion of the left upper eyelid that was found to be sebaceous cell carcinoma. Further investigation showed no metastatic disease, and Mohs surgery was performed to resect the tumor. Histopathologic analysis showed features diagnostic of sebaceous cell carcinoma. However, most of the mass consisted of xanthomatous granulomatous inflammatory reaction vastly out of proportion with the tumor burden. The patient was spared from orbital exenteration, and no evidence of recurrence was present 6 months after resection.
Assuntos
Adenocarcinoma Sebáceo/patologia , Neoplasias Palpebrais/patologia , Granuloma/patologia , Neoplasias das Glândulas Sebáceas/patologia , Xantomatose/patologia , Adenocarcinoma Sebáceo/diagnóstico por imagem , Adenocarcinoma Sebáceo/cirurgia , Idoso , Neoplasias Palpebrais/diagnóstico por imagem , Neoplasias Palpebrais/cirurgia , Granuloma/diagnóstico por imagem , Granuloma/cirurgia , Humanos , Masculino , Cirurgia de Mohs , Tomografia por Emissão de Pósitrons , Neoplasias das Glândulas Sebáceas/diagnóstico por imagem , Neoplasias das Glândulas Sebáceas/cirurgia , Tomografia Computadorizada por Raios X , Xantomatose/diagnóstico por imagem , Xantomatose/cirurgiaRESUMO
OBJECTIVES: To study the progressive changes of intense cyclic light-induced retinal degeneration and to determine whether it results in choroidal neovascularization (CNV). METHODS: Albino rats were exposed to 12 hours of 3000-lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography, fluorescein and indocyanine green angiography, and optical coherence tomography were performed prior to euthanization. Light-exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal- and nitrotyrosine-modified proteins by immunofluorescence staining. RESULTS: Long-term intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer as well as development of subretinal pigment epithelium neovascularization after 1 month. Almost the entire outer nuclear layer was absent with the presence of CNV, which penetrated the Bruch membrane and extended into the outer retina after 3 months. Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light-exposed animals showed an increased presence of 4-hydroxy-2-nonenal and nitrotyrosine staining. Optical coherence tomographic and angiographic studies confirmed retinal thinning and leakiness of the newly formed blood vessels. CONCLUSIONS: Our results suggest that albino rats develop progressive stages of retinal degeneration and CNV after long-term intense cyclic light exposure, allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration. CLINICAL RELEVANCE: The ability to study the progressive pathogenesis of age-related macular degeneration and CNV will provide detailed knowledge about the disease and aid in the development of target-specific therapy.
Assuntos
Neovascularização de Coroide/etiologia , Modelos Animais de Doenças , Luz/efeitos adversos , Lesões Experimentais por Radiação/etiologia , Retina/efeitos da radiação , Degeneração Retiniana/etiologia , Aldeídos/metabolismo , Animais , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Corantes , Feminino , Angiofluoresceinografia , Verde de Indocianina , Estresse Oxidativo , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Retina/metabolismo , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Tomografia de Coerência Óptica , Tirosina/análogos & derivados , Tirosina/metabolismoAssuntos
Neoplasias da Coroide/veterinária , Melanoma/veterinária , Doenças dos Macacos/patologia , Animais , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Coroide/metabolismo , Neoplasias da Coroide/patologia , Feminino , Angiofluoresceinografia/veterinária , Antígeno MART-1 , Macaca fascicularis , Melanoma/metabolismo , Melanoma/patologia , Antígenos Específicos de Melanoma , Doenças dos Macacos/diagnóstico por imagem , Doenças dos Macacos/metabolismo , Proteínas de Neoplasias/metabolismo , Tomografia de Coerência Óptica/veterinária , UltrassonografiaRESUMO
PURPOSE: To better understand the cellular and molecular basis for the epidemiologic association between cigarette smoke and age-related macular degeneration (AMD), the authors examined the effects of Benzo(e)Pyrene (B(e)P), a toxic element in cigarette smoke, on human retinal pigment epithelial cells (ARPE-19). METHODS: ARPE-19 cells were cultured in Dulbecco modified Eagle medium containing 10% fetal bovine serum. Cells were treated for 24 hours with 1000 microM, 400 microM, 200 microM, and 100 microM B(e)P. Cell viability was determined by a trypan blue dye-exclusion assay. Activities of caspase-3/7, caspase-8, caspase-9, and caspase-12 were measured by a fluorescence image scanner, and DNA laddering was evaluated by electrophoresis on 3% agarose gel. RESULTS: The mean percentage of cell viabilities of ARPE-19 cells was decreased in a dose-dependent manner after exposure to B(e)P at the higher concentrations of 1000 microM (20.0 +/- 0.4; P < 0.001), 400 microM (35.6 +/- 6.4; P < 0.001), and 200 microM (58.7 +/- 2.3; P < 0.001) but not at 100 microM (95.9 +/- 0.7; P > 0.05) compared with the equivalent dimethyl sulfoxide (DMSO)-treated control cultures. There were significant increases in caspase-3/7, -8, -9, and -12 activities compared with the DMSO-treated controls (P < 0.001). DNA laddering revealed bands at 200-bp intervals. CONCLUSIONS: These results show that B(e)P is a toxicant to human retinal pigment epithelial cells in vitro. It causes cell death and induces apoptosis by the involvement of multiple caspase pathways.
Assuntos
Benzopirenos/efeitos adversos , Fragmentação do DNA , Epitélio Pigmentado Ocular/efeitos dos fármacos , Poluição por Fumaça de Tabaco/análise , Apoptose , Caspases/metabolismo , Sobrevivência Celular , Células Cultivadas , DNA/efeitos dos fármacos , Eletroforese em Gel de Ágar , Humanos , Degeneração Macular/etiologia , Degeneração Macular/genética , Degeneração Macular/patologia , Epitélio Pigmentado Ocular/patologia , Fatores de RiscoAssuntos
Neoplasias da Coroide/diagnóstico , Corpo Ciliar , Glaucoma/diagnóstico , Glaucoma/metabolismo , Melanoma/diagnóstico , Pigmentos Biológicos/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Iris/metabolismo , Cápsula do Cristalino/metabolismo , Pessoa de Meia-Idade , Distribuição TecidualRESUMO
7-Ketocholesterol (7kCh) is a major oxysterol found associated with vascular diseases. Human microvascular endothelial cells (HMVECs) were cultured with different concentrations of 7kCh with and without inhibitors. Cell viabilities and caspase activities were assessed. 7kCh caused loss of cell viability in a dose-dependent manner. Caspases-8, -12, and -3/7 but not caspase-9 were activated by 7kCh treatment. The 7kCh-induced caspase-8 activity was blocked partially by pre-treatment with z-VAD-fmk and z-IETD-fmk, a caspase-8 inhibitor. However, pre-treatment with z-ATAD-fmk, a caspase-12 inhibitor, followed by 7kCh exposure lead to significantly increased caspase-8 activity. This suggests that caspase-8 and caspase-12 pathways have unique inhibition patterns and that caspase-12 is likely not upstream and feeding into caspase-8 but the pathways may function in parallel to each other. Caspase-3/7 activation was inhibited partially by low density lipoprotein (LDL), high density lipoprotein (HDL), z-VAD-fmk (pan-caspase inhibitor), and low doses (0.01 and 0.001 microM) of the cholesterol lowering drug, simvastatin. However, only LDL partially protected against 7kCh-induced loss of cell viability suggesting that caspase-independent pathways also contributed to the cell loss and that protection from oxysterol damage may require inhibition of multiple pathways. Moreover, our data suggest that oxysterols such as 7kCh can damage HMVECs cells in part via caspase-dependent apoptosis and may play a role in vascular and retinal diseases.
Assuntos
Capilares/efeitos dos fármacos , Caspases/biossíntese , Colesterol 7-alfa-Hidroxilase/antagonistas & inibidores , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Cetocolesteróis/farmacologia , Clorometilcetonas de Aminoácidos/farmacologia , Anticolesterolemiantes/farmacologia , Capilares/enzimologia , Inibidores de Caspase , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Inibidores de Cisteína Proteinase/farmacologia , Relação Dose-Resposta a Droga , Endotélio Vascular/enzimologia , Humanos , Lipoproteínas HDL/farmacologia , Lipoproteínas LDL/farmacologia , Sinvastatina/farmacologia , Pele/irrigação sanguíneaRESUMO
PURPOSE: To evaluate the short-term in vitro safety of bevacizumab (Avastin) in human retinal pigment epithelial (ARPE-19), rat neurosensory retinal (R28), and human microvascular endothelial (HMVECad) cells. METHODS: ARPE-19 and R28 cells were treated with 0.125 mg/mL, 0.25 mg/mL, 0.50 mg/mL, and 1 mg/mL of bevacizumab for 2, 6, and 24 hours. HMVECad cells were treated with 5 ng/mL of vascular endothelial growth factor (VEGF) and 0.125 mg/mL, 0.25 mg/mL, 0.50 mg/mL, and 1 mg/mL of either bevacizumab for 2, 6, and 24 hours or a nonspecific human purified immunoglobulin (IgG) for 24 hours. Cell viability was measured using trypan blue dye exclusion assay. RESULTS: The cell viabilities of ARPE-19 cells, R28 cells, and HMVECad cells treated with bevacizumab were not significantly different (P > 0.05) from that of untreated controls. There was no significant difference (P > 0.05) between viabilities of HMVECad cells treated with bevacizumab and IgG. CONCLUSION: This study suggests that bevacizumab, at concentrations at or above the dose normally used in clinical practice, is not toxic to human retinal pigment epithelial, rat neurosensory retinal, or human microvascular endothelial cells in vitro. This report is consistent with the recent report of lack of toxicity of intravitreal bevacizumab in rabbits as well as the lack of apparent toxicity in clinical use.