RESUMEN
Primary Angle Closure Glaucoma (PACG) is one of the most common types of glaucoma affecting over 15 million individuals worldwide. Family history and ethnicity are strongly associated with the development of the disease, suggesting that one or more genetic factors contribute to PACG. Although strictly heritable disease-causing mutations have not been identified, a number of recent association studies have pointed out genetic factors that appear to contribute to an individual's risk to develop PACG. In addition, genetic factors have been identified that modify PACG endophenotypes for example, axial length. Herein we review the current literature on this important topic.
Asunto(s)
Predisposición Genética a la Enfermedad , Glaucoma de Ángulo Cerrado/genética , Axones/patología , Proteínas del Ojo/genética , Ligamiento Genético , Glaucoma de Ángulo Cerrado/clasificación , Glaucoma de Ángulo Cerrado/diagnóstico , Humanos , Presión Intraocular/genética , Células Ganglionares de la Retina/patología , Factores de RiesgoRESUMEN
PURPOSE: Mutations in the forkhead transcription factor gene (FOXC1) have been recently shown to cause some cases of juvenile glaucoma associated with a variety of anterior-segment anomalies. The purpose of this study was to investigate the clinical features of Axenfeld-Rieger syndrome caused by FOXC1 mutations in Japanese patients. PATIENTS AND METHODS: After informed consent was obtained, genomic DNA was isolated from peripheral blood. The DNA-sequence changes were analyzed using single-strand conformation polymorphism analysis and automated sequencing in six Japanese probands with Axenfeld-Rieger syndrome. RESULTS: The authors identified four mutations: pedigree 1 (26-47ins22), 2 (Ile91Ser), 3 (286ins1), and 4 (Arg127His). Two pedigrees showed new mutations in FOXC1. In pedigrees 1,2, and 4, younger generations had iris hypoplasia with severe early-onset glaucoma, whereas their parents had posterior embryotoxon without glaucoma. Pedigree 3 had a single affected person with iris hypoplasia and posterior embryotoxon with a mild increase of intraocular pressure. CONCLUSION: Four different FOXC1 mutations were found in four of six Japanese pedigrees with Axenfeld-Rieger syndrome. This was a new mutation in two pedigrees that was not found in earlier generations. This study confirms that mutations in this gene cause maldevelopment of the anterior segment of the eye.
Asunto(s)
Segmento Anterior del Ojo/anomalías , Proteínas de Unión al ADN , Anomalías del Ojo/genética , Glaucoma/genética , Iris/anomalías , Mutación , Factores de Transcripción/genética , Adolescente , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Análisis Mutacional de ADN , Anomalías del Ojo/etnología , Anomalías del Ojo/cirugía , Femenino , Factores de Transcripción Forkhead , Glaucoma/etnología , Glaucoma/cirugía , Humanos , Lactante , Presión Intraocular , Japón/epidemiología , Masculino , Datos de Secuencia Molecular , Linaje , Polimorfismo Conformacional Retorcido-Simple , SíndromeAsunto(s)
Antihipertensivos/uso terapéutico , Dinoprost/uso terapéutico , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Presión Intraocular/efectos de los fármacos , Prostaglandinas F Sintéticas/uso terapéutico , Antihipertensivos/administración & dosificación , Interpretación Estadística de Datos , Dinoprost/administración & dosificación , Dinoprost/análogos & derivados , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Latanoprost , Hipertensión Ocular/tratamiento farmacológico , Soluciones Oftálmicas , Prostaglandinas F Sintéticas/administración & dosificaciónRESUMEN
PURPOSE: To evaluate long-term visual field outcome in primary open-angle glaucoma. METHODS: In this retrospective cohort study, 40 eyes of 40 patients with primary open-angle glaucoma with elevated intraocular pressure and a minimum of 8-year longitudinal series of visual fields were plotted with Goldmann perimeter. Eyes with any other ocular disease except cataract were excluded. Manual grid templates were used to quantify the visual fields. Linear regression was performed to estimate the rate of visual field decline. Pertinent clinical factors were evaluated for statistical association with the rate of decline. Long-term clinical outcome including visual acuity, rate of legal blindness, and rate of medical and surgical interventions was also measured. RESULTS: In the 40 eyes studied, with a mean follow-up of 14 years, the visual field score decreased at the rate of -1.5% per year. Overall, 68% showed significant decrease, and the rate of decrease among these eyes was -2.1% per year. Five eyes became legally blind from glaucoma; the cumulative rate of blindness from glaucoma was 19% at 22 years. Higher intraocular pressure and greater number of antiglaucoma medications on initial presentation were associated with faster and slower deterioration of visual field (compared with the average), respectively. CONCLUSIONS: With standard glaucoma therapy, the rate of visual field loss in primary open-angle glaucoma is slow. Lower intraocular pressure and more antiglaucoma medications are associated with slower visual field decline. Legal blindness from glaucoma is 19% over a follow-up of 22 years.
Asunto(s)
Glaucoma de Ángulo Abierto/metabolismo , Trastornos de la Visión/metabolismo , Agudeza Visual/fisiología , Campos Visuales , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Presión Intraocular , Modelos Lineales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trastornos de la Visión/fisiopatología , Pruebas del Campo VisualAsunto(s)
Proteínas del Ojo/genética , Glaucoma/metabolismo , Glicoproteínas/genética , Disco Óptico/metabolismo , Astrocitos/metabolismo , Western Blotting , Células Cultivadas , Proteínas del Citoesqueleto , Electroforesis en Gel Bidimensional , Proteínas del Ojo/química , Proteínas del Ojo/metabolismo , Técnica del Anticuerpo Fluorescente , Expresión Génica , Glaucoma/genética , Glicoproteínas/química , Glicoproteínas/metabolismo , Humanos , Presión Intraocular , Mutación , Disco Óptico/citología , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Mutations in the forkhead transcription-factor gene (FOXC1), have been shown to cause defects of the anterior chamber of the eye that are associated with developmental forms of glaucoma. Discovery of these mutations was greatly facilitated by the cloning and characterization of the 6p25 breakpoint in a patient with both congenital glaucoma and a balanced-translocation event involving chromosomes 6 and 13. Here we describe the identification of novel mutations in the FOXC1 gene in patients with anterior-chamber defects of the eye. We have detected nine new mutations (eight of which are novel) in the FOXC1 gene in patients with anterior-chamber eye defects. Of these mutations, five frameshift mutations predict loss of the forkhead domain, as a result of premature termination of translation. Of particular interest is the fact that two families have a duplication of 6p25, involving the FOXC1 gene. These data suggest that both FOXC1 haploinsufficiency and increased gene dosage can cause anterior-chamber defects of the eye.
Asunto(s)
Cámara Anterior/anomalías , Proteínas de Unión al ADN , Anomalías del Ojo/genética , Dosificación de Gen , Factores de Transcripción/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 6/genética , ADN/química , ADN/genética , Análisis Mutacional de ADN , Factores de Transcripción Forkhead , Duplicación de Gen , Humanos , Datos de Secuencia Molecular , Mutación , Mapeo Físico de CromosomaRESUMEN
PURPOSE: To present long-term results of eyes with penetrating keratoplasty (PK) and glaucoma tube implant. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: We retrospectively reviewed medical records of all patients who underwent both PK and glaucoma tube implant (Baerveldt or Ahmed) at the University of Iowa between July of 1988 and December of 1997 (55 eyes). METHODS: Success of the tube implant or PK was evaluated using Kaplan-Meier survival analysis. Association of relevant clinical factors with glaucoma or corneal graft outcome was evaluated using log-rank test or Cox proportional hazard regression analysis. The factors evaluated were glaucoma and cornea diagnoses; prior, simultaneous, and subsequent surgeries; type of tube implant; relative timing of surgeries; and postsurgical complications. MAIN OUTCOME MEASURES: Glaucoma outcome was assessed by postoperative intraocular pressure (IOP), number of medications, and need for further glaucoma surgery. Corneal outcome was assessed by graft rejection, failure, and Snellen visual acuity. Surgical procedures before and during the study period, and their complications were evaluated. RESULTS: The mean preoperative intraocular pressure was 29.8 mmHg with an average of 2.9 medications. At last postoperative follow-up, the mean IOP decreased to 14.3 mmHg with 0.7 medication. The tube implant successfully controlled glaucoma in 45 eyes (82%) at 3 years. More severe postsurgical complications were associated with greater glaucoma failure. Graft rejection occurred in 17 eyes, and 7 of these progressed to failure. Nonimmunologic graft failure occurred in an additional 17 eyes (31%). The remaining 31 eyes (56%) had a clear graft. The corneal grafts remained clear in 70% and 55% of eyes at 2 and 3 years, respectively. Corneal graft failure was associated with glaucoma and cornea diagnoses groups, type of tube implant, and relative timing of the two surgeries. Complications occurred in 23 eyes (42%), and 10 of these were serious. CONCLUSIONS: A drainage tube implant can successfully control glaucoma in a majority (82%) of keratoplasty eyes at 3 years. However, the success of corneal grafts is low (55%) at 3 years. Postsurgical complications are not uncommon and are associated with poor glaucoma outcome. Other clinical factors are associated with poor graft outcome.
Asunto(s)
Enfermedades de la Córnea/cirugía , Implantes de Drenaje de Glaucoma , Glaucoma/cirugía , Queratoplastia Penetrante , Enfermedades de la Córnea/complicaciones , Femenino , Estudios de Seguimiento , Glaucoma/complicaciones , Supervivencia de Injerto , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Agudeza VisualRESUMEN
Until recently, very little was known about the molecular mechanisms responsible for the development of glaucoma, a leading cause of blindness worldwide. Mutations in the glaucoma gene myocilin (MYOC, GLC1A) are associated with elevated intraocular pressure and the development of autosomal dominant juvenile glaucoma and a subset of adult-onset glaucoma. MYOC is expressed in the trabecular meshwork (TM), a tissue responsible for drainage of aqueous humor from the eye, and the tissue involved in elevated intraocular pressure associated with glaucoma. To better understand the role of MYOC in glaucoma pathogenesis, we examined the expression of normal and mutant myocilin in cultured ocular (TM) and non-ocular cells as well as in the aqueous humor of patients with and without MYOC glaucoma. Normal myocilin was secreted from cultured cells, but very little to no myocilin was secreted from cells expressing five different mutant forms of MYOC. In addition, no mutant myocilin was detected in the aqueous humor of patients harboring a nonsense MYOC mutation (Q368X). Co-transfection of cultured cells with normal and mutant myocilin led to suppression of normal myocilin secretion. These studies suggest that MYOC glaucoma is due either to insufficient levels of secreted myocilin or to compromised TM cell function caused by congestion of the TM secretory pathway.
Asunto(s)
Humor Acuoso/metabolismo , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Glaucoma/metabolismo , Glicoproteínas/genética , Glicoproteínas/metabolismo , Malla Trabecular/metabolismo , Animales , Western Blotting , Células COS , Línea Celular Transformada , Codón sin Sentido , Proteínas del Citoesqueleto , Glaucoma/genética , Humanos , Mutación , Transfección , Células Tumorales CultivadasRESUMEN
PURPOSE: Glucocorticoid-induced ocular hypertension (the steroid response) may result in optic nerve damage that very closely mimics the pathologic course of primary open angle glaucoma (POAG). In addition, patients with glaucoma and their relatives are much more likely to exhibit the steroid response than unaffected individuals, suggesting a potential link between the steroid response and POAG. Recently, the expression of a gene (MYOC) in the trabecular meshwork was shown to be steroid-induced. MYOC variations thought to be disease-causing also were found in 3% to 5% of POAG cases. The purpose of this study was to determine whether some variations in MYOC might be involved in steroid-induced ocular hypertension. METHODS: Seventy human steroid responders and 114 control subjects were screened for variations in the coding sequence and promoter of MYOC. Also, topical doses of dexamethasone (DEX) were administered to cynomolgus monkeys to determine their steroid responsiveness, and the MYOC orthologue was cloned from the cynomolgus monkey. RESULTS: Overall, 109 instances of 20 different sequence variations were identified in the human myocilin gene. However, only four of these (each observed in a single individual) met the study criteria for a possible phenotype-altering variation. Three of these were present in steroid responders and one in a control patient, a distribution that was not statistically significant (P: = 0.3). In addition, the allele frequency of a closely flanking marker was compared between the steroid responders and the control subjects, and no evidence for linkage disequilibrium was observed. Reproducible and reversible ocular hypertension was induced in approximately 40% of the monkeys treated with DEX, similar to that seen in man. Ten monkeys were screened for MYOC mutations with single-strand conformation polymorphism (SSCP) analysis. Overall, 37 instances of 13 different sequence variations were observed. Four of these changes met the study criteria for a possible phenotype-altering variation, and these were equally distributed between responder and nonresponder monkeys. CONCLUSIONS: This study identified no statistically significant evidence for a link between MYOC mutations and steroid-induced ocular hypertension.
Asunto(s)
Antiinflamatorios/efectos adversos , Proteínas del Citoesqueleto/genética , Dexametasona/efectos adversos , Proteínas del Ojo/genética , Glicoproteínas/genética , Hipertensión Ocular/inducido químicamente , Malla Trabecular/efectos de los fármacos , Administración Tópica , Adulto , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Bovinos , Proteínas del Citoesqueleto/biosíntesis , Análisis Mutacional de ADN , Cartilla de ADN/química , Proteínas del Ojo/biosíntesis , Femenino , Glucocorticoides , Glicoproteínas/biosíntesis , Humanos , Presión Intraocular , Desequilibrio de Ligamiento/genética , Macaca fascicularis , Masculino , Ratones , Datos de Secuencia Molecular , Hipertensión Ocular/genética , Hipertensión Ocular/metabolismo , Polimorfismo Conformacional Retorcido-Simple , Homología de Secuencia de Ácido Nucleico , Malla Trabecular/metabolismoRESUMEN
Rieger syndrome (RIEG 1; MIM 180500) is an autosomal dominant disorder of morphogenesis. It is a phenotypically heterogeneous disorder characterized by malformations of the eyes, teeth, and umbilicus. RIEG belongs to the Axenfeld-Rieger group of anomalies, which includes Axenfeld anomaly and Rieger anomaly (or Rieger eye malformation), which display ocular features only. Recently, mutations in the homeodomain transcription factor, PITX2, have been shown to be associated with Rieger syndrome. This review discusses the clinical manifestations of Rieger syndrome and how they correlate with the current molecular and biochemical studies on this human disorder.
Asunto(s)
Anomalías Múltiples/genética , Anomalías del Ojo/genética , Proteínas de Homeodominio/genética , Proteínas Nucleares , Anomalías Dentarias/genética , Factores de Transcripción/genética , Anomalías Múltiples/patología , Anomalías Múltiples/fisiopatología , Secuencia de Aminoácidos , Animales , Proteínas de Unión al ADN/metabolismo , Anomalías del Ojo/patología , Anomalías del Ojo/fisiopatología , Glaucoma/congénito , Glaucoma/genética , Proteínas de Homeodominio/química , Proteínas de Homeodominio/metabolismo , Humanos , Datos de Secuencia Molecular , Factores de Transcripción Paired Box , Mutación Puntual/genética , Prolactina/genética , Regiones Promotoras Genéticas/genética , Síndrome , Anomalías Dentarias/fisiopatología , Factor de Transcripción Pit-1 , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Activación Transcripcional , Proteína del Homeodomínio PITX2RESUMEN
A linkage analysis study was performed on a single large family with juvenile-onset primary open-angle glaucoma (POAG). This led to the recognition that there was a region of chromosome 1q that harboured a gene for juvenile-onset POAG. This chromosomal site was called GLC1A. It was discovered that a gene that produces the protein myocilin resides within this interval and that mutations in myocilin caused most cases of autosomal dominant juvenile-onset POAG. More importantly myocilin mutations also cause up to 4.6% of cases of adult-onset POAG. The prevalence of myocilin mutations is similar regardless of race or geographic location. There are widely variable glaucoma phenotypes depending on the specific mutation in myocilin. Myocilin is expressed in multiple tissues throughout the eye and in many other organs. In the trabecular meshwork the production of myocilin can be induced by the application of topical corticosteroids. The exact function of myocilin in health and disease remains a mystery.
Asunto(s)
Proteínas del Ojo/genética , Glaucoma de Ángulo Abierto/genética , Glicoproteínas/genética , Adulto , Proteínas del Citoesqueleto/genética , Proteínas del Ojo/metabolismo , Femenino , Ligamiento Genético , Glicoproteínas/metabolismo , Humanos , Masculino , Mutación , Linaje , Fenotipo , Malla Trabecular/metabolismoRESUMEN
PURPOSE: To review the molecular genetics of Axenfeld-Rieger syndrome and related phenotypes and to discuss how this information might affect the way that we classify these disorders. METHODS: A review of historical and recent literature on Axenfeld-Rieger syndrome and related disorders. The review includes clinical and molecular genetic literature relevant to these phenotypes. RESULTS: Three chromosomal loci have recently been demonstrated to link to Axenfeld-Rieger syndrome and related phenotypes. These loci are on chromosomes 4q25, 6p25, and 13q14. The genes at chromosomes 4q25 and 6p25 have been identified as PITX2 and FKHL7, respectively. Mutations in these genes can cause a wide variety of phenotypes that share features with Axenfeld-Rieger syndrome. Axenfeld anomaly, Rieger anomaly, Rieger syndrome, iridogoniodysgenesis anomaly, iridogoniodysgenesis syndrome, iris hypoplasia, and familial glaucoma iridogoniodysplasia all have sufficient genotypic and phenotypic overlap that they should be considered one condition. CONCLUSIONS: Axenfeld-Rieger syndrome is a term that can be used to describe a variety of overlapping phenotypes. To date, at least three known genetic loci can cause these disorders. The single most important feature of these phenotypes is that they confer a 50% or greater risk of developing glaucoma. Currently there is a fairly arbitrary grouping of disorders into small categories. Considering all of these phenotypes under the heading of Axenfeld-Rieger syndrome will allow easier communication between clinicians and scientists and eliminate arbitrary and confusing subclassification.
Asunto(s)
Segmento Anterior del Ojo/anomalías , Anomalías del Ojo/genética , Glaucoma/genética , Iris/anomalías , Proteínas Nucleares , Cromosomas Humanos Par 13/genética , Cromosomas Humanos Par 4/genética , Cromosomas Humanos Par 6/genética , Proteínas de Unión al ADN/genética , Anomalías del Ojo/historia , Factores de Transcripción Forkhead , Ligamiento Genético , Glaucoma/historia , Historia del Siglo XIX , Historia del Siglo XX , Proteínas de Homeodominio/genética , Humanos , Presión Intraocular/genética , Biología Molecular , Mutación , Factores de Transcripción Paired Box , Fenotipo , Síndrome , Factores de Transcripción/genética , Proteína del Homeodomínio PITX2RESUMEN
PURPOSE: To evaluate MYOC (myocilin) gene expression at the RNA level in normal intact human eyes and optic nerve using in situ hybridization. METHODS: Normal human eyes and optic nerves from donors 62 to 83 years of age with no history of glaucoma were fixed, embedded in paraffin, and sectioned. Sections were hybridized with (35)S-labeled sense and antisense riboprobes derived from a full-length MYOC cDNA. RESULTS: High levels of MYOC expression were observed throughout the trabecular meshwork as well as in the most anterior nonfiltering meshwork (Schwalbe's line), in the scleral spur, and in the endothelial lining of Schlemm's canal. MYOC transcripts were also detected in the anterior corneal stroma, in the ciliary muscle, beneath the anterior border of the iris, in the iris stroma, and in the sclera. Expression in the retrolaminar region of the optic nerve was present in the pial septa that divide the nerve fiber bundles, in the perivascular connective tissue surrounding the central retinal vessels, and in the dura mater, arachnoid, and pia mater of the meningeal sheath surrounding the optic nerve. CONCLUSIONS: MYOC gene expression in the trabecular meshwork, Schlemm's canal, scleral spur, and ciliary muscle indicates a structural or functional role for myocilin in the regulation of aqueous humor outflow that may influence intraocular pressure. MYOC expression in the optic nerve suggests that changes in the structural, metabolic, or neurotropic support of the optic nerve may influence its susceptibility to glaucomatous damage.
Asunto(s)
Cuerpo Ciliar/metabolismo , Proteínas del Ojo/genética , Glicoproteínas/genética , Músculo Liso/metabolismo , Nervio Óptico/metabolismo , ARN Mensajero/biosíntesis , Malla Trabecular/metabolismo , Anciano , Anciano de 80 o más Años , Northern Blotting , Proteínas del Citoesqueleto , Endotelio/metabolismo , Proteínas del Ojo/biosíntesis , Expresión Génica , Glicoproteínas/biosíntesis , Humanos , Hibridación in Situ , Persona de Mediana Edad , Esclerótica/metabolismoRESUMEN
PURPOSE: To correlate Humphrey visual field mean sensitivity and peripapillary nerve fiber layer thickness as measured by scanning laser polarimetry. METHODS: The authors studied 54 eyes of 34 patients who visited a university-based glaucoma clinic and had undergone scanning laser polarimetry and Humphrey perimetry within 6 months. The study population included normal patients and those with glaucoma, ocular hypertension, and glaucoma suspect. The authors correlated visual field sensitivity with peripapillary nerve fiber thickness, and visual field mean deviation with the average deviation from the normal nerve fiber layer thickness. They also correlated the visual field mean deviation with all available GDx Nerve Fiber Analyzer parameters. RESULTS: The visual field mean sensitivity and deviation showed a bilinear correlation to peripapillary nerve fiber layer thickness. The visual field mean sensitivity changed little when the nerve fiber layer thickness was greater than 70 microm. The nerve fiber layer thickness below this level was associated with a rapid decrease in the visual field sensitivity. Similarly, the visual field mean deviation was close to 0 dB when the nerve fiber layer was within -10 microm of the normal value; below this thickness, the mean deviation became substantially more negative. There was a large individual variability around the bilinear fit. Of the scanning laser polarimetry parameters, a calculated index, referred to as the number, had the highest correlation with the Humphrey mean deviation. CONCLUSION: The bilinear correlation and its variability between the scanning laser polarimetry and visual field parameters make it difficult to predict the result of one from the other. In general, the correlation between the two is better when there is a significant visual field defect than when the visual field is close to normal.
Asunto(s)
Glaucoma/diagnóstico , Rayos Láser , Fibras Nerviosas/patología , Disco Óptico/patología , Trastornos de la Visión/diagnóstico , Pruebas del Campo Visual/métodos , Campos Visuales , Adulto , Anciano , Síndrome de Exfoliación/diagnóstico , Síndrome de Exfoliación/fisiopatología , Femenino , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Hipertensión Ocular/diagnóstico , Hipertensión Ocular/fisiopatología , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Anterior segment developmental disorders, including Axenfeld-Rieger anomaly (ARA), variably associate with harmfully elevated intraocular pressure (IOP), which causes glaucoma. Clinically observed dysgenesis does not correlate with IOP, however, and the etiology of glaucoma development is not understood. The forkhead transcription factor genes Foxc1 (formerly Mf1 ) and Foxc2 (formerly Mfh1 ) are expressed in the mesenchyme from which the ocular drainage structures derive. Mutations in the human homolog of Foxc1, FKHL7, cause dominant anterior segment defects and glaucoma in various families. We show that Foxc1 (+/-)mice have anterior segment abnormalities similar to those reported in human patients. These abnormalities include small or absent Schlemm's canal, aberrantly developed trabecular meshwork, iris hypoplasia, severely eccentric pupils and displaced Schwalbe's line. The penetrance of clinically obvious abnormalities varies with genetic background. In some affected eyes, collagen bundles were half normal diameter, or collagen and elastic tissue were very sparse. Thus, abnormalities in extracellular matrix synthesis or organization may contribute to development of the ocular phenotypes. Despite the abnormalities in ocular drainage structures in Foxc1 (+/-)mice, IOP was normal in almost all mice analyzed, on all genetic backgrounds and at all ages. Similar abnormalities were found in Foxc2 (+/-)mice, but no disease-associated mutations were identified in the human homolog FKHL14 in 32 ARA patients. Foxc1 (+/-)and Foxc2 (+/-)mice are useful models for studying anterior segment development and its anomalies, and may allow identification of genes that interact with Foxc1 and Foxc2 (or FKHL7 and FKHL14 ) to produce a phenotype with elevated IOP and glaucoma.
Asunto(s)
Segmento Anterior del Ojo/anomalías , Proteínas de Unión al ADN/genética , Ojo/embriología , Factores de Transcripción/genética , Animales , Cuerpo Ciliar/anomalías , Proteínas de Unión al ADN/fisiología , Factores de Transcripción Forkhead , Genotipo , Glaucoma/genética , Haplotipos , Heterocigoto , Humanos , Hibridación in Situ , Presión Intraocular/genética , Ratones , Ratones Mutantes , Microscopía Electrónica , Mutagénesis , Fenotipo , Especificidad de la Especie , Factores de Transcripción/fisiologíaAsunto(s)
Glaucoma/diagnóstico , Enfermedades del Nervio Óptico/diagnóstico , Trastornos de la Visión/diagnóstico , Pruebas del Campo Visual/métodos , Campos Visuales , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Selección Visual/métodos , Pruebas del Campo Visual/normasRESUMEN
PURPOSE: To report successful use of a combination of autologous blood injection and bleb compression sutures to treat overfiltration with hypotony maculopathy after trabeculectomy with mitomycin C. METHODS: Two patients underwent the combined procedure and were followed until visual acuity and intraocular pressure (IOP) were stable over three consecutive visits (4 to 9 months). RESULTS: Both patients experienced improvement in visual acuity both subjectively and objectively, and both patients had an elevation in IOP that persisted over three consecutive visits. CONCLUSIONS: Combination autologous blood injection and bleb compression suture placement may be an effective means of treating hypotony maculopathy after trabeculectomy with mitomycin C.
Asunto(s)
Sangre , Mácula Lútea , Hipotensión Ocular/terapia , Enfermedades de la Retina/terapia , Técnicas de Sutura , Anciano , Anciano de 80 o más Años , Alquilantes/administración & dosificación , Terapia Combinada , Femenino , Glaucoma/cirugía , Humanos , Inyecciones , Presión Intraocular , Masculino , Mitomicina/administración & dosificación , Hipotensión Ocular/etiología , Hipotensión Ocular/patología , Enfermedades de la Retina/etiología , Enfermedades de la Retina/patología , Trabeculectomía/efectos adversos , Resultado del TratamientoRESUMEN
PURPOSE: To describe a case of myositis in the presence of a Baerveldt glaucoma implant. METHOD: Case report. RESULTS: A 41-year-old black woman developed myositis after placement of a Baerveldt glaucoma implant. Echography demonstrated migration of the seton plate against the medial rectus muscle insertion. Myositis resolved after removal of the Baerveldt glaucoma implant. CONCLUSION: The Baerveldt glaucoma implant may have precipitated myositis in this patient.
Asunto(s)
Migración de Cuerpo Extraño/etiología , Implantes de Drenaje de Glaucoma/efectos adversos , Miositis/etiología , Músculos Oculomotores/patología , Adulto , Femenino , Migración de Cuerpo Extraño/diagnóstico por imagen , Glaucoma de Ángulo Abierto/cirugía , Humanos , Miositis/diagnóstico por imagen , Músculos Oculomotores/diagnóstico por imagen , Reoperación , UltrasonografíaRESUMEN
The transcription factor FKHL7 gene has recently been associated with the anterior segment dysgenesis disorder of the eye known as Axenfeld-Rieger anomaly (ARA). A growing body of evidence indicates that mutations in FKHL7 cause not only defects in the anterior segment of the eye but defects in the heart valves and septa as well. In order to evaluate its contribution to normal heart septation and valve formation, expression of the mouse homologue Mf1 in embryonic hearts was analyzed by in situ hybridization. A weak but significant level of Mf1 expression could be detected in the endocardium of mouse embryos as early as day 8.5 post-conception (p.c.). Mf1 expression was undetectable in the hearts of day 9.5 p.c. embryos, but by day 10.5-11 p.c., Mf1 transcripts could be found again in the endocardium of both the atrium and ventricle and a relatively strong signal was observed in the dorsal portion of the septum primum, in what appeared to be the spinal vestibule. At day 13 p.c. when aortic and pulmonary trunks are separated, relatively more Mf1 transcripts were detected in the leaflets of aortic, pulmonary, and venous valves, the ventral portion of the septum primum, as well as in the single layer of cells on the edges of the atrioventricular cushion tissues. Surprisingly, there was no signal detected in the developing interventricular septum. At day 15 p.c., overall Mf1 signals were greatly decreased. However, significant levels of expression could still be observed in the atrial septum, the tricuspid valve, the mitral valve, and in the venous valve but not in the interventricular septum. The temporal and spatial expression patterns of the Mf1 gene in developing mouse hearts suggest that Mf1 may play a critical role in the formation of valves and septa with the exception of the interventricular septum. This is further supported by our studies showing that mutations in the FKHL7 gene were associated with defects in the anterior segment of the eye as well as atrial septal defects or mitral valve defects. Dev Dyn 1999;216:16-27.