RESUMEN
PURPOSE: To investigate the extracellular matrix and cellular components in lens capsules extracted from patients with dead bag syndrome (DBS) through immunohistochemistry. SETTING: Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan, and Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah. DESIGN: Immunohistochemical experimental study. METHODS: 9 capsular bag specimens from DBS cases, as well as 2 control specimens from late-postoperative in-the-bag intraocular lens dislocation cases related to previous vitrectomy, pseudoexfoliation, and blunt trauma were included. They were processed for histopathology; unstained sections were obtained from each one and analyzed by immunohistochemistry targeting collagen type IV, laminin, vimentin, collagen type I, and fibronectin. RESULTS: Immunohistochemistry in DBS showed lens capsule stained for basement membrane components. The outer part of the anterior capsule that was split from the inner part was more markedly stained for type IV collagen as compared with the posterior part. Faint staining for fibrous posterior capsular opacification (PCO) components, for example, collagen type I and fibronectin, was detected in limited areas, but the major portion of the capsule was free from these components. Small spotty vimentin-positive materials, suggesting the presence of cell debris, were also detected in limited samples. CONCLUSIONS: Small amounts of fibrotic PCO components were detected in capsules extracted from patients with DBS, but their major parts were free from PCO components. Current findings suggest small amounts of lens epithelial cells were present after surgery and secreted fibrous components before undergoing cell death process.
Asunto(s)
Colágeno Tipo IV , Colágeno Tipo I , Fibronectinas , Cápsula del Cristalino , Vimentina , Humanos , Colágeno Tipo IV/metabolismo , Fibronectinas/metabolismo , Masculino , Vimentina/metabolismo , Anciano , Femenino , Cápsula del Cristalino/patología , Cápsula del Cristalino/metabolismo , Persona de Mediana Edad , Colágeno Tipo I/metabolismo , Laminina/metabolismo , Subluxación del Cristalino/cirugía , Subluxación del Cristalino/diagnóstico , Subluxación del Cristalino/metabolismo , Anciano de 80 o más Años , Facoemulsificación , Síndrome de Exfoliación/metabolismo , Opacificación Capsular/metabolismo , Técnicas para Inmunoenzimas , Síndrome , Implantación de Lentes Intraoculares , AdultoAsunto(s)
Interleucina-1/biosíntesis , Subluxación del Cristalino/diagnóstico , Cristalino/diagnóstico por imagen , Retinitis Pigmentosa/complicaciones , Electrorretinografía , Humanos , Subluxación del Cristalino/etiología , Subluxación del Cristalino/metabolismo , Masculino , Persona de Mediana Edad , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/metabolismo , Microscopía con Lámpara de HendiduraRESUMEN
Cystathionine-ß-synthase (CBS) gene encodes L-serine hydrolyase which catalyzes ß-reaction to condense serine with homocysteine (Hcy) by pyridoxal-5'-phosphate helps to form cystathionine which in turn is converted to cysteine. CBS resides at the intersection of transmethylation, transsulfuration, and remethylation pathways, thus lack of CBS fundamentally blocks Hcy degradation; an essential step in glutathione synthesis. Redox homeostasis, free-radical detoxification and one-carbon metabolism (Methionine-Hcy-Folate cycle) require CBS and its deficiency leads to hyperhomocysteinemia (HHcy) causing retinovascular thromboembolism and eye-lens dislocation along with vascular cognitive impairment and dementia. HHcy results in retinovascular, coronary, cerebral and peripheral vessels' dysfunction and how it causes metabolic dysregulation predisposing patients to serious eye conditions remains unknown. HHcy orchestrates inflammation and redox imbalance via epigenetic remodeling leading to neurovascular pathologies. Although circular RNAs (circRNAs) are dominant players regulating their parental genes' expression dynamics, their importance in ocular biology has not been appreciated. Progress in gene-centered analytics via improved microarray and bioinformatics are enabling dissection of genomic pathways however there is an acute under-representation of circular RNAs in ocular disorders. This study undertook circRNAs' analysis in the eyes of CBS deficient mice identifying a pool of 12532 circRNAs, 74 exhibited differential expression profile, â¼27% were down-regulated while most were up-regulated (â¼73%). Findings also revealed several microRNAs that are specific to each circRNA suggesting their roles in HHcy induced ocular disorders. Further analysis of circRNAs helped identify novel parental genes that seem to influence certain eye disease phenotypes.
Asunto(s)
Cistationina betasintasa/genética , Hiperhomocisteinemia/metabolismo , Subluxación del Cristalino/metabolismo , ARN/metabolismo , Animales , Cistationina betasintasa/metabolismo , Epigenómica , Perfilación de la Expresión Génica , Masculino , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/fisiología , ARN CircularRESUMEN
PURPOSE: Primary lens luxation (PLL) in dogs is an inherited disease in which the lens is displaced from its normal position. A truncating mutation in the ADAMTS17 orthologue on CFA03 is reported to cause PLL in several breeds, mostly terriers. However, the complex inheritance pattern of PLL in miniature bull terriers (MBTs) suggests that other loci may have a modifying effect on the ADAMTS17 mutation. This study aimed to detect such loci increasing risk of PLL in Australian MBTs. METHODS: More than 170,000 single-nucleotide polymorphisms (SNPs) across the canine genome were genotyped in 23 PLL-affected and 73 normal Australian MBTs, and association between the PLL phenotype and the genetic markers was investigated by using general mixed effects Cox model survival analysis. RESULTS: The highest association peaks, other than that associated with the ADAMTS17 mutation (P = 2.2e-05), were SNP BICF2G630420272 located at 62.2 Mb on chromosome 15 (P = 7.8e-05) and the region between 30 Mb and 32.5 Mb on chromosome 1 (P = 9.3e-05). Joint analysis showed that the PLL-associated allele of the BICF2G630420272 SNP increased risk of PLL in the presence of the ADAMTS17 mutation (P = 8.117e-04). Candidate genes in the two regions of interest included CPE on chromosome 15 and CTGF on chromosome 1. The ADAMTS17 mutation was also associated with abnormal foot and nail shapes, pedal hyperkeratosis, and persistent pupillary membranes. CONCLUSIONS: Two loci with potentially enhancing effects on the ADAMTS17 mutation were associated with PLL in Australian MBTs. Association of the ADAMTS17 mutation with possible pedal skeletal abnormalities in MBTs supports PLL in this breed and Weill-Marchesani syndrome-like disease in humans as being homologous diseases.
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Proteínas ADAM/genética , ADN/genética , Enfermedades de los Perros/genética , Subluxación del Cristalino/genética , Cristalino/metabolismo , Mutación , Proteínas ADAM/metabolismo , Proteínas ADAMTS , Animales , Análisis Mutacional de ADN , Perros , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genotipo , Subluxación del Cristalino/metabolismo , FenotipoRESUMEN
PURPOSE: To investigate the rate of lens subluxation following plasmin and/or SF6 injections in eyes, and whether a subsequent elevated level of vascular endothelial growth factor (VEGF) and vitreous tap would aggravate subluxation. METHODS: Four groups of rabbits were used. Group 1 received an intravitreal injection (IVI) of plasmin and SF6 in the right eye; group 2 received an IVI of plasmin in the right eye; group 3 received an IVI of SF6 in the right eye; and group 4 received an IVI of balanced salt solution in the right eye. After treatment, IVIs of VEGF were given and vitreous tap was performed three times, followed by clinical observation of lens subluxation and scanning electronic microscope evaluation of the zonular fibers. RESULTS: After IVIs of plasmin and SF6, and VEGF and vitreous tap had been performed one to three times, lens subluxation was noted in 0%, 43%, 71%, 71%, and 86% of the eyes in group 1. After IVIs of plasmin, VEGF, and vitreous tap had been performed one to three times, lens subluxation was noted in 11%, 22%, 44%, 44%, and 67% of the eyes in group 2. The eyes in group 3 and 4 did not show signs of lens subluxation after VEGF IVIs and vitreous tap. Histology confirmed zonular fiber damage in the eyes treated with plasmin. CONCLUSIONS: The incidence of lens subluxation increased following plasmin injections in the eyes, and this was aggravated by the subsequent high VEGF level in the eyes and vitreous tapping. Zonular fibers were disrupted following plasmin treatment. These effects should be kept in mind when using plasmin enzymes in patients with vitreoretinal abnormalities.
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Fibrinolisina/farmacología , Subluxación del Cristalino/patología , Cristalino/efectos de los fármacos , Hexafluoruro de Azufre/farmacología , Animales , Inyecciones Intravítreas , Subluxación del Cristalino/metabolismo , Cristalino/patología , Microscopía Electrónica de Rastreo , Conejos , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacología , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/patología , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/farmacologíaAsunto(s)
Subluxación del Cristalino/etiología , Cristalino/efectos de la radiación , Síndrome de Marfan/complicaciones , Dispositivos de Protección de los Ojos , Fibrilinas , Humanos , Subluxación del Cristalino/metabolismo , Subluxación del Cristalino/prevención & control , Cristalino/metabolismo , Síndrome de Marfan/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Proteínas de Microfilamentos/metabolismo , Rayos UltravioletaAsunto(s)
Subluxación del Cristalino/etiología , Cristalino/metabolismo , Síndrome de Marfan/complicaciones , Metaloproteinasas de la Matriz/metabolismo , Proteínas de Microfilamentos/metabolismo , Adulto , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Fibrilinas , Humanos , Técnicas para Inmunoenzimas , Subluxación del Cristalino/metabolismo , Ligamentos/metabolismo , Síndrome de Marfan/metabolismo , Microfibrillas/metabolismo , Inhibidores Tisulares de Metaloproteinasas/metabolismoRESUMEN
PURPOSE: Penetration of piperacillin into the vitreous cavity after intravenous administration was investigated in humans. METHODS: Forty-five eyes undergoing vitrectomy between November 1993 and December 1994 were included. Each patient received a single intravenous dose of piperacillin 4 g 2 hours before ocular incision. A 0.2-mL vitreous sample was aspired at the beginning of vitrectomy, a blood sample was obtained, and piperacillin level was assessed. RESULTS: There were no detectable drug concentrations in 25 eyes. Mean vitreous drug concentration in the remaining evaluable eyes (n = 14) was 2.33 microg/mL (+/-0.76). We divided samples into two groups: 23 uninflamed (Group 1) and 16 inflamed (Group 2) eyes. Mean vitreous drug concentration was 0.42 microg/mL in Group 1 and 4.95 microg/mL in Group 2 (P < 0.2). Piperacillin concentration was higher than the minimum inhibitory concentration for gram-positive bacteria in 13% of uninflamed and 69% of inflamed eyes (P < 0.001). CONCLUSION: Studies show that intravenously administered piperacillin can penetrate the vitreous cavity in rabbits. Our study suggests that a single dose of piperacillin can produce intravitreal concentrations sufficient to kill gram-positive bacteria in inflamed eyes. The poor intraocular penetration of systemically administered piperacillin in uninflamed eyes raises questions about its usefulness as a prophylactic agent in ophthalmic surgery.
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Penicilinas/farmacocinética , Piperacilina/farmacocinética , Cuerpo Vítreo/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Cuerpos Extraños en el Ojo/metabolismo , Cuerpos Extraños en el Ojo/cirugía , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/prevención & control , Femenino , Humanos , Inyecciones Intravenosas , Subluxación del Cristalino/metabolismo , Subluxación del Cristalino/cirugía , Masculino , Persona de Mediana Edad , Penicilinas/administración & dosificación , Piperacilina/administración & dosificación , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/cirugía , Estudios Retrospectivos , Vitrectomía , Cuerpo Vítreo/cirugía , Hemorragia Vítrea/metabolismo , Hemorragia Vítrea/cirugíaRESUMEN
Transformation of the secondary conformational structure of the human lens capsule after traumatic lens subluxation in a patient was investigated by Fourier transform infrared (FT-IR) microscopic spectrometry. The result was compared with the IR spectra of type IV collagen in crystalline state, solid film and aqueous solution and those of the excised and dried lens capsule under compression or treated with ethyl alcohol. The results indicate that the IR spectra of the intact human lens capsule after traumatic lens subluxation were the same as those of the rabbit lens capsule, except in the 1,100-1,000 cm-1 proteoglycan region, but were different from those of type IV collagen aqueous solution at the amide I and II bands and the proteoglycan region, although type IV collagen is a predominant component of lens capsule. Two new peaks at 1,054 and 1,023 cm-1 appeared on the IR spectra of the intact human lens capsule and on those of type IV collagen in crystalline state and solid film after compression but not in normal rabbit lens capsule and native type IV collagen. It was also found that all the IR spectra of the excised and dried lens capsule were similar to those of native type IV collagen in crystalline state and solid film.(ABSTRACT TRUNCATED AT 250 WORDS)