RESUMEN
Fragile X Syndrome (FXS), the most common inherited form of human intellectual disability, is a monogenic neurodevelopmental disorder caused by a loss-of-function mutation of the FMR1 gene. FMR1 is encoding the Fragile X Messenger Ribonucleo Protein (FMRP) an RNA-binding protein that regulates the translation of synaptic proteins. The absence of FMRP expression has many important consequences on synaptic plasticity and function, leading to the FXS clinical phenotype. Over the last decade, a visual neurosensorial phenotype had been described in the FXS patients as well as in the murine model (Fmr1-/ymice), characterized by retinal deficits associated to retinal perception alterations. However, although the transcriptomic profile in the absence of FMRP has been studied in the cerebral part of the central nervous system (CNS), there are no actual data for the retina which is an extension of the CNS. Herein, we investigate the transcriptomic profile of mRNA from whole retinas of Fmr1-/ymice. Interestingly, we found a specific signature of Fmrp absence on retinal mRNA expression with few common genes compared to other brain studies. Gene Ontology on these retinal specific genes demonstrated an enrichment in retinal development genes as well as in synaptic genes. These alterations could be linked to the reported retinal phenotype of the FXS condition. In conclusion, we describe for the first time, retinal-specific transcriptomic changes in the absence of FMRP.
Asunto(s)
Modelos Animales de Enfermedad , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil , Retina , Transcriptoma , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Animales , Ratones , Retina/metabolismo , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratones Endogámicos C57BL , Perfilación de la Expresión Génica , Ratones Noqueados , Regulación de la Expresión Génica/fisiología , MasculinoRESUMEN
To prevent ocular pathologies, new generation of dietary supplements have been commercially available. They consist of nutritional supplement mixing components known to provide antioxidative properties, such as unsaturated fatty acid, resveratrol or flavonoids. However, to date, few data evaluating the impact of a mixture mainly composed of those components (Nutrof Total®) on the retina are available. Only one in-vivo preclinical study demonstrated that dietary supplementation (DS) prevents the retina from light-induced retinal degeneration; and only one in-vitro study on Müller cells culture showed that glutamate metabolism cycle was key in oxidative stress response. Therefore, we raised the question about the in-vivo effect of DS on glutamate metabolism in the retina. Herein, we showed that the dietary supplementation promotes in-vivo increase of retinal glutamine amount through a higher glutamine synthesis as observed in-vitro on Muller cells. Therefore, we can suggest that the promotion of glutamine synthesis is part of the protective effect of DS against retinal degeneration, acting as a preconditioning mechanism against retinal degeneration.
Asunto(s)
Antioxidantes , Suplementos Dietéticos , Ácidos Grasos Omega-3 , Glutamina , Retina , Degeneración Retiniana , Glutamina/metabolismo , Animales , Antioxidantes/farmacología , Ácidos Grasos Omega-3/administración & dosificación , Degeneración Retiniana/metabolismo , Degeneración Retiniana/prevención & control , Retina/metabolismo , Retina/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Células Cultivadas , Células Ependimogliales/metabolismo , Células Ependimogliales/efectos de los fármacos , Masculino , Ratas , Modelos Animales de EnfermedadRESUMEN
Four new HLA-B alleles were identified in Brazilian individuals using next generation sequencing.
Asunto(s)
Médula Ósea , Donantes de Tejidos , Humanos , Brasil , Alelos , Trasplante de Médula Ósea , Secuenciación de Nucleótidos de Alto Rendimiento , Antígenos HLA-B/genéticaRESUMEN
HLA-DQB1*02:211 allele differs from DQB1*02:02:01:02 by change of C â A in exon 2.
Asunto(s)
Alelos , Exones , Cadenas beta de HLA-DQ , Donantes de Tejidos , Humanos , Cadenas beta de HLA-DQ/genética , Brasil , Prueba de Histocompatibilidad , Trasplante de Médula Ósea , Secuencia de Bases , Análisis de Secuencia de ADN/métodos , Codón , Médula ÓseaRESUMEN
The novel HLA-DPB1*14:01:15 allele differs from DPB1*14:01:01:01 by change of C > T in exon 3.
Asunto(s)
Alelos , Secuencia de Bases , Exones , Cadenas beta de HLA-DP , Prueba de Histocompatibilidad , Donantes de Tejidos , Humanos , Cadenas beta de HLA-DP/genética , Brasil , Análisis de Secuencia de ADN/métodos , Médula Ósea , Alineación de Secuencia , Codón , Trasplante de Médula ÓseaRESUMEN
The new HLA-DRB3*03:69 allele differs from DRB3*03:01:01:03 by change of C â G in exon 3.
Asunto(s)
Alelos , Exones , Cadenas HLA-DRB3 , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad , Humanos , Secuencia de Bases , Codón , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Prueba de Histocompatibilidad/métodos , Cadenas HLA-DRB3/genética , Alineación de Secuencia , Análisis de Secuencia de ADN/métodosRESUMEN
We identified two new HLA-DRB3 alleles in Brazilian individuals using next generation sequencing.
Asunto(s)
Médula Ósea , Humanos , Cadenas HLA-DRB3 , Alelos , BrasilRESUMEN
HLA-A*68:190:02 differs from A*68:190:01 by a single synonymous nucleotide change in exon 2.
Asunto(s)
Médula Ósea , Humanos , Alelos , Brasil , Exones/genéticaRESUMEN
The new HLA-DPA1*01:182 allele differs from HLA-DPA1*01:03:01:04 by a single mismatch in exon 4.