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1.
Doc Ophthalmol ; 133(1): 71-9, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27245454

RESUMEN

PURPOSE: We aimed to describe four cases with an acquired unilateral negative electroretinogram (ERG) and severe unilateral photophobia and assess the underlying pathology. METHODS: We performed a retrospective chart view of the four cases by visiting two independent hospitals. RESULTS: Over the last 10 years, a 65-year-old man, 71-year-old woman, 68-year-old man, and 73-year-old woman presented to the hospitals with unilateral photophobia. Symptom onset was relatively obvious in all the patients. Comprehensive examinations, including visual acuity and visual field assessment, optical coherence tomography, and fluorescein angiography, showed minimal change in the eye with photophobia. However, only in the affected eye, the mixed rod-cone response in full-field ERG showed a markedly electronegative pattern, namely the amplitude of a-wave was preserved and larger than that of b-wave, and the rod and cone responses were very low. In fact, the cone responses were almost absent in all four patients. ERG findings indicate dysfunction of both rod and cone visual pathways, and the preserved a-wave in the mixed rod-cone ERG suggests that the disturbance of the rod visual pathway exists in post-photoreceptors. Moreover, although multifocal ERG showed a very low amplitude in the entire area, the preservation of the responses was detected to some extent only in the center. These symptoms and examination findings remained unchanged for more than 4 years. CONCLUSIONS: Four patients with acquired unilateral negative ERG associated with severe photophobia showed similar clinical findings. To our knowledge, no known disorders can explain these conditions.


Asunto(s)
Electrorretinografía/métodos , Fotofobia/fisiopatología , Anciano , Femenino , Angiografía con Fluoresceína , Humanos , Masculino , Células Fotorreceptoras de Vertebrados , Células Fotorreceptoras Retinianas Conos/fisiología , Células Fotorreceptoras Retinianas Bastones/fisiología , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Campos Visuales/fisiología
3.
Jpn J Ophthalmol ; 50(5): 417-425, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17013693

RESUMEN

PURPOSE: To determine whether apoptosis of retinal neurons induced by excessive light exposure and ischemia-reperfusion injury is altered in caspase-1 knockout mice. METHODS: Eight- to 10-week-old caspase-1 knockout mice (Casp1-/-) and wild-type (WT) mice (C57BL/6) were exposed to diffuse, cool, white fluorescent light of 25,000 lux for 2 h. Other mice were subjected to retinal ischemia by increasing the intraocular pressure to 110 mmHg for 45 min. Electroretinograms (ERGs) were recorded before and after the light exposure. TdT-dUTP terminal nick-end labeling (TUNEL) was performed to identify the apoptotic cells after the insults. The inner retinal thickness was measured to evaluate the retinal injury after the ischemia-reperfusion. Expression of caspase-1 protein was studied by immunohistochemical analysis and Western blotting. Caspase-1-like protease activity was determined by a colorimetric tetrapeptide substrate. RESULTS: The morphology of the retina and the amplitudes of the a and b waves of the ERGs of Casp1-/- mice did not differ from those of WT mice. After the light exposure, TUNEL-positive cells were observed in the outer nuclear layer of the WT mice retina. The number of TUNEL-positive photoreceptor nuclei after the light exposure, and the number of nuclei in the inner nuclear layer after the ischemia-reperfusion injury, were significantly less in Casp1-/- mice than in WT mice. There were more caspase-1-positive photoreceptor cells in WT mice after the light injury. The inner retinal layer of Casp1-/- mice was significantly thicker in Casp1-/- mice than in WT mice 2 weeks after the ischemic insult. CONCLUSIONS: Retinal neuronal apoptosis was less prominent in Casp1-/- mice after excessive light exposure and ischemia-reperfusion injury. These data indicate that caspase-1 plays a role in retinal neuronal apoptosis.


Asunto(s)
Apoptosis/fisiología , Caspasa 1/metabolismo , Mutación , Neuronas/citología , Retina/citología , Animales , Western Blotting , Caspasa 1/genética , ADN/genética , Modelos Animales de Enfermedad , Electrorretinografía , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/metabolismo , Reacción en Cadena de la Polimerasa , Retina/metabolismo
4.
Invest Ophthalmol Vis Sci ; 44(5): 2211-20, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12714663

RESUMEN

PURPOSE: To investigate genes that are up- and downregulated in rat retinal ischemia-reperfusion injury systematically by using an oligonucleotide microarray system and to determine temporal and spatial expression changes of some genes that showed upregulation in the analysis. METHODS: Retinal ischemia was induced in rats by increasing intraocular pressure to 110 mm Hg for 1 hour. Gene expression at 12 hours after reperfusion was compared with that in the control retina by using oligonucleotide microarrays that display a total of 8800 genes and expressed sequence tags (ESTs). Temporal and spatial expression changes of immediate early genes and cell-cycle-related genes were studied by using real-time polymerase chain reaction (PCR) and immunohistochemical methods. RESULTS: At 12 hours after reperfusion, 135 genes and ESTs were found to be up- or downregulated. The upregulated genes were classified into seven groups: (1) immediate early genes; (2) cell-cycle-related genes; (3) stress-responsive protein genes; (4) cell-signaling protein genes; (5) cell-adhesion and cell surface protein genes; (6) genes for translation and protein turnover; and (7) genes for metabolism. Real-time PCR analyses showed peaks of Fra-1 expression at 6 hours after reperfusion, whereas those for c-Jun, Jun B, and cyclin D1 were at 24 hours. Fra-1 and Jun B immunoreactivities were found in Müller cells, whereas c-Jun and cyclin D1 immunoreactivities were found in apoptotic retinal neurons. CONCLUSIONS: Gene expression changes after a retinal ischemia-reperfusion injury were profiled by using an oligonucleotide microarray system. Seven groups of genes were found to be upregulated by the injury. Among the immediate early genes, Fra-1 and Jun B immunoreactivities were found in Müller cells whereas c-Jun and cyclin D1 immunoreactivities were found in apoptotic retinal neurons.


Asunto(s)
Genes Inmediatos-Precoces/genética , Neuronas/metabolismo , ARN Mensajero/metabolismo , Daño por Reperfusión/metabolismo , Retina/metabolismo , Enfermedades de la Retina/metabolismo , Animales , Proteínas de Ciclo Celular/genética , Proteínas del Ojo/genética , Técnica del Anticuerpo Fluorescente Indirecta , Expresión Génica , Perfilación de la Expresión Génica , Proteínas Inmediatas-Precoces/genética , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba
5.
Invest Ophthalmol Vis Sci ; 43(3): 744-50, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11867593

RESUMEN

PURPOSE: To determine the effect of pyrrolidine dithiocarbamate (PDTC), an antioxidant nuclear factor (NF)-kappaB inhibitor, on the ocular inflammation induced by lipopolysaccharide (LPS). METHODS: Endotoxin-induced uveitis (EIU) was produced by a footpad injection of 200 microg LPS in male Lewis rats. PDTC (200 mg/kg) was injected intraperitoneally 30 minutes before the LPS administration. The number of infiltrating cells and protein concentration in the aqueous humor (AqH) was determined from the AqH collected at 24 hours. Immunohistochemical staining with a monoclonal antibody against activated NF-kappaB was performed to evaluate the effect of PDTC on NF-kappaB activation. Interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha mRNA expression in the iris-ciliary body (ICB) was determined by RNase protection assay (RPA). The levels of these cytokines and nitric oxide (NO) production were also determined. RESULTS: The number of cells in the AqH was 1100 +/- 254 cells/microL in rats injected with LPS and 90 +/- 43 cells/microL in rats pretreated with PDTC (P < 0.001). The concentration of proteins was significantly lower in the AqH of rats pretreated with PDTC than in those without PDTC. The number of activated NF-kappaB-positive cells in the ICB was reduced by the PDTC treatment. The ICB at 6 hours after LPS injection exhibited increased expression of IL-1beta, IL-6, and TNF-alpha mRNAs, which was decreased after PDTC pretreatment. PDTC also significantly diminished the levels of these cytokines and nitrite-nitrate in the AqH. CONCLUSIONS: These results suggest that PDTC reduces ocular inflammation in eyes with EIU by downregulating proinflammatory cytokine expression and by inhibiting the NF-kappaB-dependent signaling pathway.


Asunto(s)
Antioxidantes/uso terapéutico , Lipopolisacáridos , Pirrolidinas/uso terapéutico , Salmonella , Tiocarbamatos/uso terapéutico , Uveítis Anterior/tratamiento farmacológico , Animales , Humor Acuoso/citología , Humor Acuoso/metabolismo , Cuerpo Ciliar/metabolismo , Cuerpo Ciliar/patología , Regulación hacia Abajo , Técnica del Anticuerpo Fluorescente Indirecta , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Iris/metabolismo , Iris/patología , Masculino , FN-kappa B/genética , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas Lew , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Uveítis Anterior/metabolismo , Uveítis Anterior/patología
6.
Invest Ophthalmol Vis Sci ; 44(10): 4347-56, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-14507879

RESUMEN

PURPOSE: To systematically explore changes in gene expression in the retina of monkeys with laser-induced glaucoma and to validate the microarray data on eyes with experimental glaucoma. METHODS: Glaucoma was induced in the right eye of four monkeys by repeated argon laser photocoagulation of the trabecular meshwork. The left eye served as the control. Retinas were isolated from glaucomatous and control eyes 30 days after photocoagulation. Gene expression changes were analyzed by human microarray chips which displayed a total of 9182 elements including Expression Sequence Tag (EST) clones. Changes in the expression of some genes were further confirmed by real-time PCR analysis. Immunohistochemical studies to examine protein expression of some gene products were also done for several genes that showed up- or downregulation by the microarray analysis. RESULTS: Two eyes with mild glaucoma and two with severe glaucoma were produced. In the mild and severe glaucomatous retina, the number of upregulated genes was 45 and 18, and the number of downregulated genes was 17 and 21, respectively. The number of genes that were up- or downregulated was 0.7% of all the genes examined. The real-time PCR analysis confirmed expression changes of some genes found in the microarray analysis. Ceruloplasmin was one of the upregulated genes, and it was found by immunohistochemical analyses to be expressed in Müller cells. CONCLUSIONS: Gene expression profiles in laser-induced glaucomatous monkey retinas were determined, and only a very small population of genes was up- or downregulated in glaucomatous eyes. Upregulation of ceruloplasmin protein was found in the Müller cells.


Asunto(s)
Proteínas del Ojo/genética , Perfilación de la Expresión Génica , Glaucoma/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Retina/metabolismo , Animales , Ceruloplasmina/metabolismo , Modelos Animales de Enfermedad , Técnica del Anticuerpo Fluorescente Indirecta , Glaucoma/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Presión Intraocular , Coagulación con Láser , Macaca fascicularis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Malla Trabecular/cirugía , Regulación hacia Arriba
7.
Invest Ophthalmol Vis Sci ; 45(11): 4226-32, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15505079

RESUMEN

PURPOSE: To investigate the protective roles played by heme oxygenase (HO)-1 and -2 in the rat retina after ischemia-reperfusion injury. METHODS: Retinal ischemia was induced in rats by increasing the intraocular pressure to 110 mmHg for 60 minutes. The expression of HO-1 and -2 in the retina was determined by Western blot, real-time polymerase chain reaction (PCR), and immunohistochemistry. To inhibit the upregulation of HO-1, short interfering (si)RNA of HO-1 was injected intravitreally before ischemia and that of green fluorescent protein (GFP) was used as the control. Muller cell damage was assessed by counting the number of S-100-positive cells. The number of macrophages invading the retina was determined by counting the number of ED-1-positive cells. RESULTS: The expression of HO-1 mRNA and protein was upregulated at 6 hours after reperfusion and peaked at 12 to 24 hours, whereas that of HO-2 was not altered. HO-1 immunoreactivities were detected in Muller cells at 24 hours after reperfusion, and HO-2 immunoreactivities were detected in retinal cells. The HO-1 expression in the retina treated with siRNA of HO-1 was reduced at 12 and 24 hours after reperfusion compared with that injected with siRNA of GFP. The number of S-100-positive cells at 24 hours after reperfusion decreased significantly in retinas treated with HO-1 siRNA (P <0.01). The number of macrophages that had infiltrated the retina was increased in retinas pretreated with the siRNA of HO-1 compared with those treated with siRNA of GFP. On day 14 after reperfusion, HO-1 siRNA-treated retinas showed severe retinal injury and destruction of the retinal architecture. CONCLUSIONS: HO-1 promotes the survival of Muller cells after ischemia-reperfusion injury. Because inhibition of the upregulation of HO-1 resulted in an infiltration of inflammatory cells and destruction of the retina, the authors conclude that HO-1 induced in Muller cells plays a protective role in retinal ischemia-reperfusion.


Asunto(s)
Hemo Oxigenasa (Desciclizante)/fisiología , Neuroglía/enzimología , Daño por Reperfusión/prevención & control , Enfermedades de la Retina/prevención & control , Animales , Western Blotting , Supervivencia Celular , Ectodisplasinas , Hemo-Oxigenasa 1 , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Masculino , Proteínas de la Membrana/metabolismo , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , ARN Interferente Pequeño/farmacología , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/enzimología , Enfermedades de la Retina/enzimología , Proteínas S100/metabolismo , Regulación hacia Arriba
8.
J Biochem ; 131(6): 861-8, 2002 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12038983

RESUMEN

PTB-like protein (PTBLP) is a new homologue of pyrimidine tract binding protein (PTB), and has been cloned as a possible autoantigen in cancer-associated retinopathy. PTBLP has two functional domains, the nuclear localization signal and the RNA recognition motifs (RRMs). Full-length PTBLP (PTBLP-L) has four RRMs, and its alternative splicing product (PTBLP-S) lacks the third and fourth RRMs. Although PTBLPs are expressed in neuronal tissues, the function of PTBLPs has not been determined. We have studed whether PTBLP plays a role in neuronal differentiation using PC12 cells. During the process of nerve growth factor-induced neuronal differentiation of PC12 cells, PTBLP-L was down-regulated whereas PTBLP-S was up-regulated. Transfection of PTBLP-L into PC12 cells led to the suppression of neuronal differentiation. In PTBLP-S transfected cells, however, this suppression was not evident. When both PTBLP-L and PTBLP-S were co-transfected, the suppressive effect of PTBLP-L decreased. In differentiated cells, PTBLP-S localized in the nucleus and PTBLP-L was found dispersed throughout the cytoplasm and neuronal growth cone. These findings suggest that PTBLP-L acts as a negative regulator of neuronal differentiation and PTBLP-S acts as a competitor of PTBLP-L.


Asunto(s)
Diferenciación Celular/fisiología , Neuronas/citología , Proteína de Unión al Tracto de Polipirimidina/fisiología , Animales , Factor de Crecimiento Nervioso/farmacología , Proteínas de Neurofilamentos/biosíntesis , Neuronas/efectos de los fármacos , Neuronas/fisiología , Células PC12 , Proteína de Unión al Tracto de Polipirimidina/genética , Proteínas de Unión al ARN/fisiología , Ratas , Transfección
9.
Am J Ophthalmol ; 138(4): 567-73, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15488782

RESUMEN

PURPOSE: To study the genotypes, allelic frequencies, and polymorphisms of apolipoprotein E (Apo E) in unrelated Japanese patients with polypoidal choroidal vasculopathy (PCV) or exudative age-related macular degeneration (AMD) and control subjects without macular degeneration. DESIGN: Cross-sectional study. METHODS: Blood samples from 225 subjects older than 50 years were used. The 225 subjects included 58 patients with PCV, 85 with AMD, and 82 without macular degeneration. Coding exons of the Apo E gene were amplified by polymerase chain reaction, and the DNA sequences were determined by direct sequencing with an automated sequencer. RESULTS: Apo E epsilon3/epsilon3 was the most frequent genotype with a prevalence of 79.3% in PCV patients, 76.5% in AMD patients, and 67.1% in the control subjects. However, the differences in the percentages were not statistically significant among the three groups. The most frequently found allele in the three groups was epsilon3. Patients with PCV and AMD were less likely to have epsilon2 and epsilon4 than the control subjects, but the differences were not statistically significant. Five minor Apo E single nucleotide polymorphisms, including epsilon5 and epsilon7, were found. CONCLUSION: Japanese patients with PCV and AMD were less likely to have epsilon2 and epsilon4 polymorphisms, but the differences from the normals were not statistically significant for the Apo E genotypes and allelic frequencies.


Asunto(s)
Apolipoproteínas E/genética , Enfermedades de la Coroides/genética , Coroides/irrigación sanguínea , Degeneración Macular/genética , Polimorfismo Genético , Anciano , Anciano de 80 o más Años , Alelos , Enfermedades de la Coroides/etnología , Estudios Transversales , ADN/análisis , Femenino , Angiografía con Fluoresceína , Frecuencia de los Genes , Humanos , Japón/epidemiología , Degeneración Macular/etnología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa
10.
Retin Cases Brief Rep ; 8(1): 17-20, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25372200

RESUMEN

PURPOSE: To describe a patient with Hodgkin disease with posterior uveitis who also had a thinning of the retina and an antiretinal autoantibody in his serum. METHODS: Our patient was a 58-year-old man who had been diagnosed with Hodgkin disease. He had a complete ophthalmologic examination including fluorescein angiography, electroretinography, perimetry, and spectral-domain optical coherence tomography. A search for antiretinal antibodies in the serum was made by Western blot analysis, and the retinal sites reactive to the antibodies were determined by immunohistochemistry. RESULTS: The ocular signs were mild cellular infiltration in the anterior chamber and vitreous, and small, round chorioretinal lesions in the peripheral retina. The electroretinograms were slightly reduced. Small ring-like scotomas were detected in the Goldmann visual fields. An antiretina-specific 116-kDa antibody was detected in the serum by Western blot analysis, and the antibody reacted with the ganglion cell and inner nuclear layers of mice retinas. Although the visual acuities were maintained for over eight years, the macular thickness measured in the spectral-domain optical coherence tomography images was reduced. CONCLUSION: The presence of an antiretinal autoantibody, granulomatous uveitis, and retinal thinning in a patient with Hodgkin disease suggests that the patient had a granulomatous uveitis associated with Hodgkin disease or lymphoma-associated uveitis with retinal involvement.


Asunto(s)
Enfermedad de Hodgkin/complicaciones , Enfermedades de la Retina/etiología , Uveítis Posterior/etiología , Autoanticuerpos/sangre , Humanos , Masculino , Persona de Mediana Edad , Retina/inmunología , Enfermedades de la Retina/inmunología , Uveítis Posterior/inmunología
11.
Invest Ophthalmol Vis Sci ; 54(8): 5424-31, 2013 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-23860756

RESUMEN

PURPOSE: To report the clinical and immunological characterization of paraneoplastic retinopathy (PR) and to investigate the association between spectral-domain optical coherence tomography (SDOCT) findings and the targets of autoantibodies in PR. METHODS: We retrospectively enrolled eight patients (age range, 57-85 years; four men and four women) suspected of having PR. All patients underwent comprehensive ophthalmic examinations, including best-corrected visual acuity (BCVA) measurement, slitlamp examinations, kinetic visual field testing with Goldmann perimetry, electroretinography (ERG), fundus photography, fluorescein angiography, fundus autofluorescence (FAF), SDOCT, and serum sample tests (Western blot analysis and immunohistochemistry [IHC]). RESULTS: Three patients had a history of malignant tumors, and four patients were newly diagnosed as having neoplastic tumors (small cell lung carcinoma [SCLC], thymoma, pancreatic neuroendocrine neoplasm, and colon cancer). Another de novo malignancy (SCLC) was detected in a patient with a history of malignancy (bladder cancer and liposarcoma). The BCVA in these patients ranged from hand motion to 1.5. Goldmann perimetry revealed island, ring-shaped, concentric, or central scotoma. All patients showed nonrecordable or reduced amplitude results on ERG. Fluorescein leakage was detected in five patients. Hyperautofluorescence and/or hypoautofluorescence on FAF was detected in six patients. The serum sample tests identified anti-retinal antibodies in all patients. Patients whose serum contained anti-photoreceptor or anti-retinal pigment epithelium antibody on IHC showed damage of the outer retina on SDOCT. CONCLUSIONS: In this case series, PR was associated with a variety of neoplasms and autoantibodies. Spectral-domain OCT can be used to characterize morphologic changes, and the changes were associated with the targets of autoantibodies.


Asunto(s)
Autoanticuerpos/inmunología , Proteínas del Ojo/inmunología , Síndromes Paraneoplásicos , Enfermedades de la Retina/diagnóstico , Epitelio Pigmentado de la Retina/inmunología , Anciano , Anciano de 80 o más Años , Western Blotting , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Enfermedades de la Retina/inmunología , Enfermedades de la Retina/metabolismo , Epitelio Pigmentado de la Retina/patología , Estudios Retrospectivos , Tomografía de Coherencia Óptica
13.
Retin Cases Brief Rep ; 6(2): 159-62, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-25390951

RESUMEN

PURPOSE: The purpose of this study was to report our findings on a patient with cancer-associated retinopathy who had seminoma. METHODS: A 43-year-old man, who had been diagnosed with Stage 1 seminoma, complained of blurred vision. Fundus examination revealed attenuated retinal arteries, mild optic disk pallor, and a thinning of the outer nuclear layer. Ring scotomas were found in the visual fields of both eyes. The amplitudes of the electroretinograms were moderately reduced. The patient's serum was analyzed for antibodies. RESULTS: Antibodies against recoverin, Hu, and Ma-2 antigens were not detected. However, Western blots of the serum detected 2 bands at 41 and 64 kDa. The 41-kDa band was an anti-retina-specific antibody. Immunoreactivity was identified in the photoreceptor layer of mice retinas. From these findings, we diagnosed the patient with cancer-associated retinopathy. The visual functions remained stable after the removal of the primary lesion at an early stage, treatment with steroids, and intravenous immunoglobulin. CONCLUSION: This is the first case of cancer-associated retinopathy because of seminoma. The progression of the disease was reduced by removing the seminoma at an early stage, treatment with steroids, and intravenous immunoglobulin.

14.
Invest Ophthalmol Vis Sci ; 51(7): 3554-9, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20570996

RESUMEN

PURPOSE. micro-Crystallin (CRYM) is a major taxon-specific lens protein. The purpose of this study was to investigate the function of CRYM in eyes of mice with endotoxin-induced uveitis (EIU). METHODS. EIU was induced by an injection of a lipopolysaccharide (LPS) into the footpad of male C57BL/6J, CRYM knockout (CRYM(-/-)), and wild-type (CRYM(+/+)) mice. The expression of CRYM in the iris-ciliary body (ICB) was investigated by Western blot analyses and real-time RT-PCR at 12 hours and 1, 3, and 5 days after the LPS injection. The number of cells that had infiltrated the anterior chamber (AC) of the CRYM(+/+) mice was compared to that in the CRYM(-/-) mice at 1, 3, 5, and 7 days. The expressions of the mRNA of interleukin (IL)-1alpha, IL-6, tumor necrosis factor (TNF)-alpha, and granulocyte macrophage-colony stimulating factor (GM-CSF) in the ICB of the two groups of mice were compared. RESULTS. The mRNA of CRYM was upregulated at 12 hours after LPS injection, and CRYM protein increased at 3 days. The number of inflammatory cells in the AC of the CRYM(-/-) mice was not significantly different on day 1 from that in the CRYM(+/+) mice, but was significantly lower (17.9 +/- 1.6 vs. 27.1 +/- 2.4 cells/section) on day 5. Expression of the mRNA of IL-1alpha and -6 in the CRYM(-/-) mice was significantly lower than that in the CRYM(+/+) mice on day 5. CONCLUSIONS. CRYM plays an important role in the development of the second peak of murine EIU.


Asunto(s)
Cuerpo Ciliar/metabolismo , Cristalinas/fisiología , Iris/metabolismo , Lipopolisacáridos/toxicidad , Salmonella typhimurium , Uveítis Anterior/metabolismo , Animales , Western Blotting , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/fisiología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Interleucina-1alfa/genética , Interleucina-6/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/genética , Uveítis Anterior/inducido químicamente , Cristalinas mu
15.
Ocul Immunol Inflamm ; 17(3): 142-7, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19585355

RESUMEN

PURPOSE: The authors investigate the efficacy of using the cytokine levels and clonal heavy-chain immunoglobulin (IgH) gene rearrangements in the vitreous as adjunctive tools to diagnose intraocular lymphoma (IOL). METHODS: The IL-10 and IL-6 levels and IgH gene rearrangements were analyzed in vitreous samples from 8 cases of IOL and in 14 uveitis patients. RESULTS: The level of IL-10 with an IL-10/IL-6 ratio > 1 was significantly higher in all eyes with IOL. B-cell monoclonality was detected in only 5 of 8 eyes with IOL. CONCLUSIONS: The measurements of the levels of cytokines are valuable as a reliable biomarker.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Reordenamiento Génico de Cadena Pesada de Linfocito B/genética , Cadenas Pesadas de Inmunoglobulina/genética , Linfoma de Células B/diagnóstico , Neoplasias de la Retina/diagnóstico , Cuerpo Vítreo/patología , Anciano , Anciano de 80 o más Años , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Mediciones Luminiscentes , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Neoplasias de la Retina/genética , Neoplasias de la Retina/metabolismo , Uveítis/diagnóstico , Uveítis/genética , Uveítis/metabolismo , Vitrectomía , Cuerpo Vítreo/metabolismo
17.
Exp Eye Res ; 80(3): 401-12, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15721622

RESUMEN

The purposes of this study are to determine the genes that are up- or down-regulated in eyes with endotoxin-induced uveitis (EIU) by an oligonucleotide microarray system, and to determine the temporal and spatial changes in expression of selected genes that show strong up-regulation. EIU was induced by a footpad injection of lipopolysaccharide (LPS) in male Lewis rats. The expression of genes in the iris-ciliary body (ICB) at 2, 6, 12, and 24 hr after LPS injection was determined by oligonucleotide microarray analyses and compared to that in control rats. The microarray displayed 9911 genes and expressed sequence tags (ESTs). Cluster analysis was performed for highly up-regulated genes. Selected genes for cytokines (interleukin (IL)-1 beta and IL-6), chemokines (RANTES), and immediate early genes (Jun B, c-Fos, and c-Jun) were also studied by real-time polymerase chain reaction (PCR). Immunohistochemical studies were performed to localize the protein expression of some immediate early gene products. After LPS injection, the expression of 1930 genes were increased or decreased over 2-folds compared with normal controls by 24 hr. One hundred and seventeen genes were up-regulated over 10-fold, and these were classified into five clusters with similar expression pattern. The immediate early genes and transcription factors genes were included in one cluster of up-regulated genes peaking at 2 hr after the LPS injection. The expressions of cytokines, chemokines, and adhesion molecules were highly up-regulated. Real-time PCR analyses for selected genes showed similar expression changes as detected by the microarray analyses. Jun B immunoreactivity was found in the ICB cells at 3 and 6 hr after LPS injection. Gene expression changes after LPS injection were profiled by using an oligonucleotide microarray system. Our data suggest that the immediate early genes, such as Jun B, play an important role in inducing the inflammatory-related genes in the ICB.


Asunto(s)
Cuerpo Ciliar/fisiología , Regulación de la Expresión Génica/genética , Iris/fisiología , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Uveítis/genética , Animales , Humor Acuoso/química , Humor Acuoso/citología , Análisis por Conglomerados , Regulación hacia Abajo/genética , Proteínas del Ojo/análisis , Inmunohistoquímica/métodos , Lipopolisacáridos , Masculino , ARN Mensajero/análisis , Ratas , Ratas Endogámicas Lew , Factores de Tiempo , Regulación hacia Arriba/genética
18.
Exp Eye Res ; 77(6): 665-73, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14609554

RESUMEN

Endotoxin-induced uveitis (EIU) is an animal model of acute ocular inflammation. Cytokines, chemokines, and nitric oxide (NO) have been reported to play important roles. We have determined whether heme oxygenase (HO)-1, a heat shock protein, can suppress EIU. EIU was induced by a footpad injection of lipopolysaccharide (LPS) in male Lewis rats. Hemin, an inducer of HO-1, was injected intraperitoneally 1 hr prior to the LPS injection. HO-1 and HO-2 expression in the iris-ciliary body (ICB) was studied by real time PCR and Western blot analysis. The number of infiltrating cells and the protein concentration in the aqueous humor (AqH) were evaluated by microscopy and by protein assay. The expression of inducible nitric oxide synthase (iNOS), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and IL-1beta mRNA was determined by real time PCR. The concentration of nitrate plus nitrite, and levels of IL-6 and TNF-alpha in the AqH were also evaluated by Griess reagents and by enzyme-linked immunosorbent assay, respectively. The expression of HO-1 mRNA and protein, induced by LPS, was enhanced significantly by pre-injection of hemin (P<0.001). HO-2 was constitutively present in the ICB and was not up-regulated by LPS or by hemin. The number of infiltrating cells and the concentration of protein in the AqH was significantly elevated by LPS injection, and hemin significantly reduced the number of cells and the protein concentration (P<0.0001). The expression of iNOS and IL-6 mRNA and protein were down-regulated by hemin (P<0.001). Hemin is effective in inducing HO-1 and in reducing the ocular inflammation induced by LPS probably by down-regulating NO and pro-inflammatory cytokine expression.


Asunto(s)
Hemo Oxigenasa (Desciclizante)/metabolismo , Uveítis/enzimología , Animales , Humor Acuoso/metabolismo , Western Blotting/métodos , Cuerpo Ciliar/enzimología , Modelos Animales de Enfermedad , Regulación hacia Abajo , Proteínas del Ojo/análisis , Expresión Génica/efectos de los fármacos , Hemo Oxigenasa (Desciclizante)/análisis , Hemo-Oxigenasa 1 , Hemina/farmacología , Interleucina-6/análisis , Iris/enzimología , Lipopolisacáridos , Masculino , Óxido Nítrico/biosíntesis , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/análisis , Ratas , Ratas Endogámicas Lew , Factor de Necrosis Tumoral alfa/análisis
19.
Ophthalmology ; 110(10): 2040-4, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-14522785

RESUMEN

PURPOSE: To report cases of Blau syndrome with a CARD15/Nod2 mutation. DESIGN: Observational and interventional case report. PARTICIPANTS: A 10-year-old Japanese boy (proband) was seen with secondary angle-closure glaucoma (iris bombe), uveitis, skin rashes, and camptodactyly. His sister had posterior synechia and camptodactyly. She had iritis in both eyes during the follow-up period. Both eyes of the father were phthisical because of granulomatous uveitis and secondary glaucoma. The father also had camptodactyly. METHODS: Surgery was performed to release the iris bombe. Ocular inflammation was treated by topical and systemic steroids. Biopsy specimens from the skin rash and from the iris (from iridectomy) were obtained from the proband. Genetic analyses were performed on the proband, his sister, and their mother for a CARD15/Nod2 mutation. MAIN OUTCOME MEASURES: Clinical features, pathologic findings of the skin and iris specimens, and genetic analysis of the CARD15/Nod2 gene. RESULTS: Phacoemulsification, intraocular lens implantation, and peripheral iridectomy released the iris bombe. The biopsy specimen from the skin rash showed noncaseating, granulomatous infiltration with epithelioid cells and lymphocytes. The iridectomy specimen showed nonspecific inflammation. Systemic and topical steroid therapy partly reduced the ocular inflammation. Genetic analyses showed that the proband and his sister had an R334W mutation in the CARD15/Nod2 gene, but their mother was of the wild type. CONCLUSIONS: Blau syndrome should be considered in the differential diagnosis of childhood uveitis. Genetic analysis of the CARD15/Nod2 gene is helpful in the diagnosis.


Asunto(s)
Artritis/genética , Proteínas Portadoras/genética , Exantema/genética , Péptidos y Proteínas de Señalización Intracelular , Artropatías/genética , Mutación Puntual , Uveítis/genética , Artritis/diagnóstico , Artritis/tratamiento farmacológico , Niño , Exantema/diagnóstico , Exantema/tratamiento farmacológico , Femenino , Glaucoma de Ángulo Cerrado/genética , Glaucoma de Ángulo Cerrado/cirugía , Glucocorticoides/uso terapéutico , Humanos , Iridectomía , Iritis/tratamiento farmacológico , Iritis/genética , Artropatías/diagnóstico , Artropatías/tratamiento farmacológico , Implantación de Lentes Intraoculares , Masculino , Persona de Mediana Edad , Proteína Adaptadora de Señalización NOD2 , Facoemulsificación , Síndrome , Uveítis/diagnóstico , Uveítis/tratamiento farmacológico
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