RESUMEN
Purpose: To describe a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) with secondary angle closure caused by ciliary body thickening accompanied by intraocular pressure (IOP) elevation after mydriasis. Observations: A 55-year-old woman with a history of ovarian cancer had blurred vision in both eyes. Fundus examination revealed multiple patchy lesions in both eyes and a nevus-like elevated lesion in the right eye. Anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) demonstrated angle closure resulting from ciliary body thickening. After mydriasis, the IOP was elevated in both eyes. Instillation of a miotic drug successfully reversed the IOP to normal levels. Conclusions and Importance: BDUMP caused secondary angle closure in both eyes, presumably due to thickening of the entire ciliary body. AS-OCT and UBM were advantageous for analyzing the morphology of the anterior eye segment in BDUMP. Clinicians should be aware of the possibility of angle closure during the management of patients with BDUMP.
RESUMEN
PURPOSE: To estimate the central 10-degree visual field of glaucoma patients using en-face images obtained by optical coherence tomography (OCT), and to examine its usefulness. PATIENTS AND METHODS: Thirty-eight eyes of 38 patients with primary open angle glaucoma were examined. En-face images were obtained by swept-source OCT (SS-OCT). Nerve fiber bundles (NFBs) on en-face images at points corresponding to Humphrey Field Analyzer (HFA) 10-2 locations were identified with retinal ganglion cell displacement. Estimated visual fields were created based on the presence/absence of NFBs and compared to actual HFA10-2 data. κ coefficients were calculated between probability plots of visual fields and NFBs in en-face images. RESULTS: Actual HFA10-2 data and estimated visual fields based on en-face images were well matched: when the test points of <5%, <2%, and <1% of the probability plot in total deviation (TD) and pattern deviation (PD) of HFA were defined as points with visual field defects, the κ coefficients were 0.58, 0.64, and 0.66 in TD, respectively, and 0.68, 0.69, and 0.67 in PD. In eyes with spherical equivalent ≥ -6 diopters, κ coefficients for <5%, <2%, and <1% were 0.58, 0.62, and 0.63 in TD and 0.66, 0.67, and 0.65 in PD, whereas for the myopic group with spherical equivalent < -6 diopters, the values were 0.58, 0.69, and 0.71 in TD and 0.72, 0.71, and 0.71 in PD, respectively. There was no statistically significant difference in κ coefficients between highly myopic eyes and eyes that were not highly myopic. CONCLUSIONS: NFB defects in en-face images were correlated with HFA10-2 data. Using en-face images obtained by OCT, the central 10-degree visual field was estimated, and a high degree of concordance with actual HFA10-2 data was obtained. This method may be useful for detecting functional abnormalities based on structural abnormalities.
Asunto(s)
Glaucoma de Ángulo Abierto/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Pruebas del Campo Visual/métodos , Campos Visuales , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miopía/diagnóstico por imagen , Fibras Nerviosas/patología , Células Ganglionares de la Retina/patología , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: We evaluated the rate of progression of total, upper, and lower visual field defects in patients with treated primary open-angle glaucoma (POAG) with high myopia (HM). SUBJECTS AND METHODS: Seventy eyes of 70 POAG patients with HM [≤-8 diopters (D)] were examined. The mean deviation (MD) slope and the upper and lower total deviation (upper TD, lower TD) slopes of the Humphrey Field Analyzer were calculated in patients with high-tension glaucoma (HTG) (>21 mmHg) versus normal-tension glaucoma (NTG) (≤21 mmHg). The mean age of all the patients (29 eyes with HTG and 41 eyes with NTG) was 48.5 ± 9.6 years. The MD slope, and upper and lower TD slopes of the HM group were compared to those of the non-HM group (NHM) (>-8 D) selected from 544 eyes in 325 age-matched POAG patients. In all, 70 eyes with HM and NHM were examined. RESULTS: The mean MD slope was -0.33 ± 0.33 dB/year in the HM, and -0.38 ± 0.49 dB/year in the NHM. There were no statistical differences between the HM and NHM (p = 0.9565). In the comparison of HTG versus NTG patients in both groups, the MD slope, and upper and lower TD slopes were similar. CONCLUSIONS: The rate of progression of total, upper, and lower visual field defects was similar among patients with HM and NHM. Although HM is a risk factor for the onset of glaucoma, HM may not be a risk factor for progression of visual field defects as assessed by the progression rate under treatment.
Asunto(s)
Glaucoma de Ángulo Abierto/diagnóstico , Miopía Degenerativa/diagnóstico , Trastornos de la Visión/diagnóstico , Campos Visuales/fisiología , Adulto , Progresión de la Enfermedad , Femenino , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Presión Intraocular , Glaucoma de Baja Tensión/diagnóstico , Glaucoma de Baja Tensión/fisiopatología , Masculino , Persona de Mediana Edad , Miopía Degenerativa/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Tonometría Ocular , Trastornos de la Visión/fisiopatología , Pruebas del Campo VisualRESUMEN
Purpose. To compare a new digital Goldmann applanation tonometer (dGAT) that measures intraocular pressure (IOP) in 0.1 mmHg increments to a standard Goldmann applanation tonometer (sGAT). Methods. This study included 116 eyes of 60 subjects. A single examiner first measured IOP in triplicate using either sGAT or dGAT, which was randomly chosen. After a 5-minute interval, the next set of three consecutive IOP was measured using the other GAT. Results. The mean IOP measured with sGAT was 16.27 ± 6.68 mmHg and 16.35 ± 6.69 mmHg with dGAT. Pearson's correlation coefficient was 0.998 (P < 0.01). The subjects were divided into three groups based on the mean IOP: IOP < 14 mmHg, 14-20 mmHg, or >20 mmHg. The Pearson's correlation coefficient within each group was 0.935, 0.972, and 0.997 (P < 0.01), respectively. The difference within the three consecutive IOP measurements (maximum-minimum) for dGAT (0.72 ± 0.34 mmHg) was significantly smaller than those with sGAT (0.92 ± 0.42 mmHg, P < 0.01). Even in patients with equal IOP (zero left-right difference) with sGAT (n = 30), dGAT detected IOP differences between the left and right eyes (0.47 ± 0.31 mmHg). Conclusion. Compared to sGAT, dGAT measurements are highly reproducible and less variable.
RESUMEN
PURPOSE: To report a case of acute glaucoma due to complete ring cyst of the ciliary body. PATIENTS AND METHODS: A 33-year-old woman experienced blurred vision in her left eye. Intraocular pressure of the left eye was elevated accompanied with a very shallow anterior chamber. Anterior segment-optical coherence tomography and ultrasound biomicroscopy detected ring-shaped ciliary masses in the both eyes. Myopic change and contact between the ciliary mass and lens in the left eye suggested the presence of aqueous misdirection resulting in forward displacement of the lens-iris diaphragm. Because elevated intraocular pressure was refractory to conservative management, the left eye underwent clear lens aspiration and implantation of intraocular lens. RESULTS: Although the anterior chamber became deep in the left eye initially after lens extraction in conjunction with core vitrectomy, possible aqueous misdirection recurred. Second vitrectomy in the left eye together with posterior and anterior capsulotomies, to establish humoral communication between the anterior and posterior chambers, deepened the anterior chamber and lowered the intraocular pressure. The anterior chamber in the fellow right eye remained deep a year after the episode. CONCLUSIONS: This is the first reported case of bilateral ring cysts of the ciliary body. The manifestation caused secondary glaucoma, which was resolved by lensectomy and vitrectomy.
Asunto(s)
Cuerpo Ciliar/patología , Quistes/complicaciones , Glaucoma/etiología , Enfermedades de la Úvea/complicaciones , Enfermedad Aguda , Adulto , Quistes/diagnóstico , Femenino , Glaucoma/cirugía , Gonioscopía , Humanos , Presión Intraocular , Implantación de Lentes Intraoculares , Cristalino/cirugía , Microscopía Acústica , Recurrencia Local de Neoplasia , Tomografía de Coherencia Óptica , Enfermedades de la Úvea/diagnóstico , VitrectomíaRESUMEN
We describe a method that enables the introduction of 2 suture loops for scleral fixation of an intraocular lens (IOL) by a single ab externo procedure. A long needle carrying a polypropylene suture loop is inserted through the scleral fixation site and docked with a hollow needle inserted through the opposite fixation site. The hollow needle pulls the suture needle out, but the suture loop end is left external. Another polypropylene suture loop is placed through the first loop. As the first (leading) suture is pulled, the second (trailing) suture is drawn into the eye. The suture loops are retrieved through the main incision. The IOL haptics are secured with a polypropylene loop by cow hitches. After the IOL is placed in the eye, the sutures are fixated to the sclera. This technique enhances efficiency and control during the introduction of suture loops for scleral fixation of IOLs.
Asunto(s)
Implantación de Lentes Intraoculares/métodos , Polipropilenos , Esclerótica/cirugía , Técnicas de Sutura , Suturas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Facoemulsificación/métodos , Agudeza Visual/fisiologíaRESUMEN
BACKGROUND: Reading performance in glaucoma patients has yet to be studied. We hypothesized that glaucomatous visual field loss affects reading performance even in patients with good acuity and evaluated their reading performance quantitatively. METHODS: A cross-sectional, comparative, non-interventional study. Forty-nine patients with early-moderate glaucomatous visual field loss OU with visual acuity better than 1.0 in the better and 0.7 in the worse eye. Reading performance in glaucoma patients was examined by the Japanese version of the Minnesota Reading Acuity Chart (MNREAD) were compared to that of age-matched normal subjects (n = 30). RESULTS: The study subjects consisted of the 21 men and 28 women. The mean age was 53.3 ± 12.6 years. Diagnosis included primary open-angle glaucoma (n = 22), normal-tension glaucoma (n = 22), developmental glaucoma (n = 4) and exfoliation glaucoma (n = 1). Reading parameters of glaucoma patients examined by MNREAD were: maximum reading speed (MRS), 329.9 ± 55.4 characters per min.; critical print size (CPS), 0.24 ± 0.14 logMAR; reading acuity (RA), 0.02 ± 0.12 log MAR, significantly lower than those of normal subjects (MRS 363.0 ± 42.9, CPS 0.09 ± 0.13 logMAR, RA -0.13 ± 0.10 logMAR, P < 0.01 for three parameters by unpaired t test). CPS in glaucoma subjects was negatively correlated with mean deviation of Humphrey Field Analyzer 10-2 and 30-2 programs in the better eye (r = -0.402, P < 0.005; r = -0.304, P < 0.05; respectively, by linear regression analysis). CONCLUSIONS: The reading performance deteriorated even in glaucoma patients with good acuity.
Asunto(s)
Síndrome de Exfoliación/fisiopatología , Glaucoma de Ángulo Abierto/fisiopatología , Glaucoma de Baja Tensión/fisiopatología , Lectura , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis y Desempeño de Tareas , Trastornos de la Visión/fisiopatología , Pruebas de Visión/instrumentación , Agudeza Visual/fisiología , Campos Visuales/fisiologíaRESUMEN
PURPOSE: The purpose of this study was to analyze the relationship between the mean deviation (MD) slope as the progressive rate of visual field defects and the follow-up intraocular pressure (IOP) in open-angle glaucoma (OAG) patients. METHODS: This study was a retrospective, nonrandomized comparative study. A total of 287 eyes from 287 Japanese OAG patients were examined. The MD slope of the Humphrey Field Analyzer was calculated and compared with the follow-up IOP. OAG was classified into the high-tension group (>21 mm Hg) and the normal-tension group (≤ 21 mm Hg) on the basis of the highest recorded IOP without treatment, and then the 2 groups were compared. After setting a threshold for the progression rate at -0.3 dB/y, related factors were compared between the fast-progression and slow-progression eyes in each group. RESULTS: The correlation line between the follow-up IOP and the MD slope was statistically significant in the high-tension group but not in the normal-tension group. Compared with eyes with slow progression, eyes with fast progression in the high-tension group were older and had a higher mean IOP, greater highest and lowest IOPs, and a smaller mean IOP reduction ratio, whereas eyes with fast progression in the normal-tension group had a greater SD of the mean IOP, a larger IOP range, and a greater highest IOP. CONCLUSIONS: Eyes with a faster visual field progression tended to have a higher follow-up IOP in the high-tension group and larger IOP fluctuations in the normal-tension group of OAG patients. We should monitor both the follow-up IOP and fluctuations in IOP to provide a safer and more reliable visual field prognosis for OAG.
Asunto(s)
Glaucoma de Ángulo Abierto/diagnóstico , Presión Intraocular/fisiología , Glaucoma de Baja Tensión/diagnóstico , Trastornos de la Visión/diagnóstico , Campos Visuales/fisiología , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Glaucoma de Ángulo Abierto/fisiopatología , Gonioscopía , Humanos , Glaucoma de Baja Tensión/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tonometría Ocular , Trastornos de la Visión/fisiopatología , Pruebas del Campo VisualRESUMEN
PURPOSE: To evaluate binocular and monocular reading ability in glaucoma patients with good visual acuity and to examine its relationship with central visual field sensitivity. METHODS: Glaucoma patients(35 individuals, mean +/- SD : 51.8 +/- 12.9 years) with a decimal visual acuity in each eye of >or=1.0, reading ability was tested both binocular and monocular using Japanese version of Minnesota Reading Acuity Chart (MNREAD-J). Reading ability parameters were calculated for maximum reading speed (MRS), critical print size (CPS), and reading acuity (RA). The results were compared with those of people with normal vision; differences in reading ability under varied testing conditions and correlations between visual field sensitivity and each parameter were examined. RESULTS: Under binocular reading conditions, MRS, CPS, and RA were decreased significantly in glaucoma patients compared with normal controls (p = 0.00044, p = 0.00004, p = 0.00028, respectively). Under monocular reading conditions, glaucoma patient MRS and RA were decreased significantly in comparison with normal controls (p=0.00155, p= 0.00142). In glaucoma patients undergoing binocular reading tests, MRS was greatest in the paracentral bottom right quadrant of the worse eye (r = 0.41709, p= 0.04447). The CPS decreased in proportion to the extent of the difference between both eyes in the mean deviation value and the visual field sensitivity of the paracentral bottom left (r = 0.40693, p = 0.02699 and r=0.41478, p=0.02384). RA improved in proportion to the extent of the difference between both eyes in the visual field sensitivity of the upper left (r = 0.33557, p=0.04799). CONCLUSION: In glaucoma patients, binocular reading is not necessarily useful in cases of visual field sensitivity differences.
Asunto(s)
Glaucoma/fisiopatología , Lectura , Visión Binocular/fisiología , Visión Monocular/fisiología , Campos Visuales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To investigate the incidence of adverse effects on eyelids and eyelashes related to treatment with prostaglandin analogs (PGAs) in patients who apply the medication in only one eye. METHODS: A clinical examination of 39 glaucoma patients treated for over 3 months continuously in one eye with one of four PGAs. Face photographs were used to judge adverse effects of PGA treatment on eyelids and eyelashes of the treated eyes by comparing them with the eyelids and eyelashes of the contralateral eyes. Each of three examiners then calculated scores for the eyelids and eyelashes by counting how many adverse effects were present (out of five possible effects for eyelids and two for eyelashes). The findings for the eyelids or eyelashes were considered "positive" if two or more examiners judged that at least one adverse effect was present. RESULTS: Thirty-five (89.7 %) patients were judged to have positive eyelid findings and 37 (94.9 %) patients were judged to have positive eyelash findings. There was a significant correlation between the period of PGA administration and eyelid score (P = 0.0218). CONCLUSION: There was a high incidence of adverse effects caused by PGAs in the eyelids and eyelashes. The frequency of adverse effects of the eyelid seemed to increase as the use of PGAs was prolonged. The cosmetic complications caused by PGA use should be considered, and patients should be informed of them in advance.
Asunto(s)
Antihipertensivos/efectos adversos , Pestañas/efectos de los fármacos , Enfermedades de los Párpados/inducido químicamente , Glaucoma/tratamiento farmacológico , Enfermedades del Cabello/inducido químicamente , Prostaglandinas Sintéticas/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de los Párpados/diagnóstico , Femenino , Enfermedades del Cabello/diagnóstico , Humanos , Incidencia , Presión Intraocular/efectos de los fármacos , Masculino , Persona de Mediana Edad , Soluciones Oftálmicas , Fotograbar , Estudios RetrospectivosRESUMEN
PURPOSE: The herb rosemary has been reported to have antioxidant and anti-inflammatory activity. We have previously shown that carnosic acid (CA), present in rosemary extract, crosses the blood-brain barrier to exert neuroprotective effects by upregulating endogenous antioxidant enzymes via the Nrf2 transcriptional pathway. Here we investigated the antioxidant and neuroprotective activity of CA in retinal cell lines exposed to oxidative stress and in a rat model of light-induced retinal degeneration (LIRD). METHODS: Retina-derived cell lines ARPE-19 and 661W treated with hydrogen peroxide were used as in vitro models for testing the protective activity of CA. For in vivo testing, dark-adapted rats were given intraperitoneal injections of CA prior to exposure to white light to assess protection of the photoreceptor cells. Retinal damage was assessed by measuring outer nuclear layer thickness and by electroretinogram (ERG). RESULTS: In vitro, CA significantly protected retina-derived cell lines (ARPE-19 and 661W) against H(2)O(2)-induced toxicity. CA induced antioxidant phase 2 enzymes and reduced formation of hyperoxidized peroxiredoxin (Prx)2. Similarly, we found that CA protected retinas in vivo from LIRD, producing significant improvement in outer nuclear layer thickness and ERG activity. CONCLUSIONS: These findings suggest that CA may potentially have clinical application to diseases affecting the outer retina, including age-related macular degeneration and retinitis pigmentosa, in which oxidative stress is thought to contribute to disease progression.
Asunto(s)
Abietanos/uso terapéutico , Estrés Oxidativo , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Degeneración Retiniana/prevención & control , Animales , Antioxidantes/uso terapéutico , Barrera Hematoencefálica/efectos de los fármacos , Línea Celular , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Electrorretinografía , Luz/efectos adversos , Células Fotorreceptoras de Vertebrados/patología , Células Fotorreceptoras de Vertebrados/efectos de la radiación , Ratas , Ratas Sprague-Dawley , Degeneración Retiniana/etiología , Degeneración Retiniana/metabolismo , RosmarinusRESUMEN
BACKGROUND/AIMS: To analyse quantitatively the anterior segment configuration in eyes with nanophthalmos before and after cataract surgery. METHODS: This was a retrospective, non-comparative, interventional case series. Eleven eyes in eight patients with nanophthalmos who underwent phacoemulsification and intraocular lens implantation were identified from the department's surgical log, and their clinical records were retrospectively reviewed. Main outcome measures were as follows: visual acuity, intraocular pressure (IOP), axial length and the following ultrasound biomicroscopy parameters: angle opening distance at 500 µm anterior to the scleral spur (AOD500), trabecular-iris angle (TIA) and trabecular ciliary process distance. RESULTS: The mean axial length of the eyes was 17.3 ± 1.7 mm. AOD500 and TIA increased after cataract surgery (p<0.005). Smaller axial length, AOD500 and TIA before cataract surgery were observed in eyes with preoperative IOP elevation than those without preoperative IOP elevation (p<0.05). Lower postoperative IOP was correlated with greater AOD500 and TIA before cataract surgery (p<0.05). CONCLUSIONS: Cataract surgery deepened the anterior chamber and widened the anterior chamber angle in nanophthalmic eyes. Cataract surgery may have beneficial effects on IOP in eyes with nanophthalmos.
Asunto(s)
Cámara Anterior/diagnóstico por imagen , Cuerpo Ciliar/diagnóstico por imagen , Iris/diagnóstico por imagen , Implantación de Lentes Intraoculares , Microftalmía/cirugía , Facoemulsificación , Adulto , Anciano , Longitud Axial del Ojo/patología , Femenino , Humanos , Presión Intraocular/fisiología , Masculino , Microscopía Acústica , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Agudeza Visual/fisiologíaRESUMEN
BACKGROUND: Fibrin pupillary-block glaucoma is a rare complication after cataract surgery. The treatment for this condition is still controversial, since Nd:YAG laser fibrin membranotomy tends to reocclude and laser peripheral iridotomy entails the risk of damaging the corneal endothelium in the presence of corneal edema associated with elevated intraocular pressure. CASE PRESENTATION: A 62-year-old man with diabetes mellitus developed acute elevation of intraocular pressure with a shallow anterior chamber five days after uneventful cataract surgery. Initially, slit lamp examination provided only limited information due to severe corneal edema. After resolution of corneal edema with systemic glaucoma therapy, a complete fibrin membrane was observed across the pupil by slit lamp examination. Anterior segment optic coherence tomography clearly revealed a thin fibrin membrane covering the entire pupillary space, a shallow anterior chamber, and a deep posterior chamber. The intraocular lens was not observed by anterior segment optic coherence tomography. In contrast, ultrasound biomicroscopy, which has superior penetration depth, was able to visualize the intraocular lens deep in the posterior chamber. Injection of tissue plasminogen activator into the anterior chamber resulted in complete fibrinolysis and released the pupillary block. CONCLUSION: This case suggests that ocular anterior segment imaging modalities, especially ultrasound biomicroscopy, serve as powerful diagnostic tools to identify mechanisms of acute angle closure glaucoma, which is often accompanied by poor intraocular visibility. This is the first reported case of fibrin pupillary-block glaucoma after cataract surgery successfully treated with intracameral tissue plasminogen activator.
Asunto(s)
Extracción de Catarata/efectos adversos , Fibrina/metabolismo , Glaucoma de Ángulo Cerrado/tratamiento farmacológico , Trastornos de la Pupila/tratamiento farmacológico , Activador de Tejido Plasminógeno/administración & dosificación , Fibrina/efectos de los fármacos , Glaucoma de Ángulo Cerrado/diagnóstico , Glaucoma de Ángulo Cerrado/etiología , Humanos , Inyecciones Intraoculares , Masculino , Persona de Mediana Edad , Trastornos de la Pupila/diagnósticoRESUMEN
Many genetic differences have been found among currently available BCG vaccines. To avoid continued accumulation of phenotypic or genotypic changes in the strains, WHO and most national regulatory authorities request that the vaccine should not be prepared by more than 12 passages from the master seed lot. However, it has recently been reported that genetic changes occur even during the passage for vaccine production. In this study, the genetic stability of Japanese BCG vaccine production using currently available PCR methods and protective efficacy using a guinea-pig model during the passages were examined. The results showed that there were no significant differences between the seed lot, the product manufactured by normal procedures, and the 20th passage product. These results indicate that the maximum number of passages as currently required by WHO for BCG vaccine production is adequate for the Japanese vaccine, and that new genetic tools may help to examine the quality control of the BCG vaccine.
Asunto(s)
Vacuna BCG/genética , Vacuna BCG/inmunología , Inestabilidad Genómica , Mycobacterium bovis/crecimiento & desarrollo , Mycobacterium bovis/genética , Pase Seriado , Animales , Carga Bacteriana , ADN Bacteriano/genética , Modelos Animales de Enfermedad , Femenino , Cobayas , Humanos , Japón , Pulmón/microbiología , Reacción en Cadena de la Polimerasa , Tuberculosis/prevención & controlRESUMEN
Activation of the Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and consequent induction of phase 2 antioxidant enzymes is known to afford neuroprotection. Here, we present a series of novel electrophilic compounds that protect neurons via this pathway. Natural products, such as carnosic acid (CA), are present in high amounts in the herbs rosemary and sage as ortho-dihydroquinones, and have attracted particular attention because they are converted by oxidative stress to their active form (ortho-quinone species) that stimulate the Keap1/Nrf2 transcriptional pathway. Once activated, this pathway leads to the production of a series of antioxidant phase 2 enzymes. Thus, such dihydroquinones function as redox-activated 'pro-electrophiles'. Here, we explored the concept that related para-dihydroquinones represent even more effective bioactive pro-electrophiles for the induction of phase 2 enzymes without producing toxic side effects. We synthesized several novel para-hydroquinone-type pro-electrophilic compounds (designated D1 and D2) to analyze their protective mechanism. DNA microarray, PCR, and western blot analyses showed that compound D1 induced expression of heat-shock proteins (HSPs), including HSP70, HSP27, and DnaJ, in addition to phase 2 enzymes such as hemeoxygenase-1 (HO-1), NADP(H) quinine-oxidoreductase1, and the Na(+)-independent cystine/glutamate exchanger (xCT). Treatment with D1 resulted in activation of Nrf2 and heat-shock transcription factor-1 (HSF-1) transcriptional elements, thus inducing phase 2 enzymes and HSPs, respectively. In this manner, D1 protected neuronal cells from both oxidative and endoplasmic reticulum (ER)-related stress. Additionally, D1 suppressed induction of 78 kDa glucose-regulated protein (GRP78), an ER chaperone protein, and inhibited hyperoxidation of peroxiredoxin 2 (PRX2), a molecule that is in its reduced state can protect from oxidative stress. These results suggest that D1 is a novel pro-electrophilic compound that activates both the Nrf2 and HSF-1 pathways, and may thus offer protection from oxidative and ER stress.
Asunto(s)
Antioxidantes/metabolismo , Proteínas de Unión al ADN/fisiología , Factor 2 Relacionado con NF-E2/fisiología , Fármacos Neuroprotectores/farmacología , Quinonas/farmacología , Epitelio Pigmentado de la Retina/enzimología , Transducción de Señal/fisiología , Factores de Transcripción/fisiología , Antioxidantes/síntesis química , Antioxidantes/fisiología , Células Cultivadas , Proteínas de Unión al ADN/metabolismo , Chaperón BiP del Retículo Endoplásmico , Factores de Transcripción del Choque Térmico , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Fármacos Neuroprotectores/síntesis química , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Quinonas/síntesis química , Epitelio Pigmentado de la Retina/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/metabolismoRESUMEN
PURPOSE: We evaluated the progression rate of total, and upper and lower visual field defects in treated open-angle glaucoma patients. PATIENTS AND METHODS: This study was a retrospective, nonrandomized, comparative study. Five-hundred forty-four eyes from 315 Japanese open-angle glaucoma patients were examined. The mean deviation (MD) and total deviation (TD) for both the upper and lower slopes on the Humphrey Field Analyzer were calculated and compared in high-tension glaucoma (>21 mmHg) and normal-tension glaucoma (≤21 mmHg). RESULTS: Patients with over -20 dB of MD and over -23 dB of upper or lower TD were enrolled into each analysis. Patients with -7.75 ± 5.30 (mean ± standard deviation) dB of MD, -9.16 ± 10.80 dB of upper TD, or -7.11 ± 6.02 dB of lower TD were followed up for 4-19 years. The mean MD slope was -0.41 ± 0.50 dB/year, the upper TD slope was -0.46 ± 0.65 dB/year, and the lower TD slope was -0.32 ± 0.53 dB/year. Comparing high-tension glaucoma and normal-tension glaucoma, the upper TD slope was similar for both types of glaucoma, but the MD and lower TD slopes in high-tension glaucoma were significantly lower than those in normal-tension glaucoma. CONCLUSIONS: The progression rates in lower visual field defects in high-tension glaucoma might be faster than those in normal-tension glaucoma. The results of this study might be used to predict the prognosis of visual field defects, as well as the quality of vision in patients with open-angle glaucoma.
RESUMEN
Current methods for the identification of BCG vaccine in quality control settings involve acid-fast staining with microscopic examination. However, this method is unable to distinguish the many different sub-strains of BCG, or to differentiate BCG strains from virulent members of the Mycobacterium tuberculosis complex. A multiplex PCR (mPCR) which uses six target regions in mycobacteria has been developed to identify specific sub-strains of BCG. This study reports the findings from an international collaborative study to assess the accuracy, robustness and reproducibility of this mPCR method to differentiate BCG sub-strains. The method was found to fulfil these criteria successfully and was able to distinguish BCG sub-strains in vaccine preparations. The majority of the participants in the study generated the expected PCR product profiles indicating the method is also robust.
Asunto(s)
Vacuna BCG/genética , Mycobacterium bovis/clasificación , Reacción en Cadena de la Polimerasa/métodos , Técnicas de Tipificación Bacteriana/métodos , ADN Bacteriano/análisis , Cooperación Internacional , Mycobacterium bovis/genética , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: This study investigated whether the enzymatically inactive caspase mimetic IQACRG protects rat retinal ganglion cells (RGCs) from excitotoxic insults. Minimally invasive delivery of the peptide to the retina was explored, and the mechanisms of neuroprotection were elucidated. METHODS: IQACRG was linked to penetratin (P-IQACRG) to facilitate cellular uptake. RGC labeling by biotinylated-P-IQACRG delivered via intravitreal or subconjunctival injection was demonstrated by avidin-biotin chemistry. The authors used histologic and electrophysiological measures to evaluate the neuroprotective potential of P-IQACRG against RGC death induced by N-methyl-D-aspartate (NMDA) in vitro and in vivo. In addition, they monitored activity of an enzyme that is downstream of caspase-1, matrix metalloproteinase-9 (MMP-9), and protein levels of the caspase-3/7 substrate, myocyte enhancer factor 2C (MEF2C), to determine the effectiveness of IQACRG in blocking excessive caspase activity. RESULTS: IQACRG significantly reduced NMDA-induced RGC death in culture and in vivo. Ex vivo electrophysiological recording of the retina on multielectrode arrays demonstrated functional rescue of RGCs by IQACRG. The authors also found that delivery of IQACRG to the retina inhibited NMDA-triggered MMP-9 activity and prevented cleavage of MEF2C protein that would otherwise have been engendered by caspase activation preceding RGC death. Strikingly, subconjunctival injection of P-IQACRG was very effective in preventing NMDA-induced RGC death in vivo. CONCLUSIONS: These data demonstrate that IQACRG protects RGCs from excitotoxicity in vitro and in vivo. The positive results with subconjunctival administration of P-IQACRG suggest that in the future this treatment may be useful clinically in diseases such as glaucoma and retinal ischemia.
Asunto(s)
Agonistas de Aminoácidos Excitadores/toxicidad , N-Metilaspartato/toxicidad , Fármacos Neuroprotectores/farmacología , Oligopéptidos/farmacología , Enfermedades de la Retina/prevención & control , Células Ganglionares de la Retina/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Caspasa 3/metabolismo , Caspasa 7/metabolismo , Inhibidores de Caspasas , Supervivencia Celular , Células Cultivadas , Electrofisiología , Técnica del Anticuerpo Fluorescente Indirecta , Técnicas para Inmunoenzimas , Etiquetado Corte-Fin in Situ , Inyecciones , Factores de Transcripción MEF2 , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Factores Reguladores Miogénicos/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Oligopéptidos/administración & dosificación , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/patología , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/patología , Cuerpo VítreoRESUMEN
Bloody stools, diarrhea and perianal abscesses were observed from the age of two months infant. The boy received a BCG vaccination at the age of four months. The patient was diagnosed as having Crohn's disease at the age of six months by intestinal endoscopy. Based on the diagnosis, he was treated with nutrition therapy, salazosulfapyridine, and prednisolone. Fever of unknown origin occurred two months after he had taken azathioprine at the age of two years and two months. Mycobacterium tuberculosis was detected from a gastric aspirate, and he was diagnosed as having disseminated BCG infection by means of the multiplex PCR method. Chest CT showed miliary pulmonary nodules in both lungs on admission. Physical examination revealed enlarged lymphnodes, which were palpable around the neck and groin, and hepatomegaly. Laboratory data were within normal ranges except a slightly increased peripheral white blood cell and serum CRP level. He was treated with rifampicin (15 mg/kg/day), isoniazid (15 mg/kg/day) for 12 months, and streptomycin (25 mg/kg/day) for two months. He became afebrile a week after starting the treatment, and the miliary pulmonary nodules in both lungs had disappeared by 5 months after starting the treatment. An abnormality of the NEMO gene, which is the gene responsible for ectodermal dysplasia and immunodeficiency, was identified at the age of three years. It is assumed that an abnormality of the NEMO gene caused a latent BCG infection over a period of one year and ten months, and immunosuppressive medicine (azathioprine) induced a disseminated BCG infection. This case report supports that anti-tuberculosis medicine should be given to prevent disseminated BCG infection if an infant who receive immunosuppressive therapy is found to have an immune deficiency characterized by a mycobacterium infection after BCG vaccination.
Asunto(s)
Vacuna BCG/efectos adversos , Enfermedad de Crohn/complicaciones , Displasia Ectodérmica/complicaciones , Síndromes de Inmunodeficiencia/complicaciones , Mycobacterium bovis , Tuberculosis/etiología , Preescolar , Humanos , Masculino , Vacunación/efectos adversosRESUMEN
The exact role of cyclooxygenase-2 (COX-2) in neurodegeneration of retinal ganglion cells (RGCs) in vivo following ischemia-reperfusion injury of the retina was unknown. We made transgenic mice in which the Thy-1.2 promoter drives the expression of EGFP cDNA (Thy-1-EGFP) in RGCs to monitor RGC survival and death in retinal whole mount preparations and in live animals. We show that celecoxib, a selective COX-2 inhibitor, blocks RGC death after ischemic injury. Furthermore, in COX-2 knockout (COX-2(-/-)) mice, RGCs are resistant to ischemia-reperfusion injury. Finally, we performed time-lapse monitoring of RGC death after ischemia in Thy-1-EGFP; COX-2(-/-) mice. Our data show that COX-2 plays a crucial role in ischemia-reperfusion injury-induced RGC death. Inhibition of COX-2 activity may therefore be an effective therapy for neurodegenerative diseases of the retina and optic nerve.