Research Interests: Nonparametric Statistics, Neurochemistry, Membrane Proteins, Gait, Brain, and 21 moreCollagen, Mice, Animals, Spinal Cord, Acetylcholinesterase, Acetylcholine, Neurons, Cholinesterase inhibitors, Body Temperature, Microdialysis, Tritium, Pyridines, Exploratory Behavior, Radioisotopes, Choline, Protein Binding, Maze Learning, Neurosciences, Gene Expression Regulation, Cholinergic agents, and Motor activity(Collagen, Mice, Animals, Spinal Cord, Acetylcholinesterase, Acetylcholine, Neurons, Cholinesterase inhibitors, Body Temperature, Microdialysis, Tritium, Pyridines, Exploratory Behavior, Radioisotopes, Choline, Protein Binding, Maze Learning, Neurosciences, Gene Expression Regulation, Cholinergic agents, and Motor activity)
(Collagen, Mice, Animals, Spinal Cord, Acetylcholinesterase, Acetylcholine, Neurons, Cholinesterase inhibitors, Body Temperature, Microdialysis, Tritium, Pyridines, Exploratory Behavior, Radioisotopes, Choline, Protein Binding, Maze Learning, Neurosciences, Gene Expression Regulation, Cholinergic agents, and Motor activity)
1 Neovacs 3/5 Impasse Reille Paris France; 2 Institut Pasteur, Paris; 3 Université Paris 13, Hôpital Avicenne AP-HP, Bobigny, France; 4 Centre de Recherche Thérapeutique en Ophtalmologie, Université Paris-Descartes, Paris; 5 ULB-IBMM,... more
1 Neovacs 3/5 Impasse Reille Paris France; 2 Institut Pasteur, Paris; 3 Université Paris 13, Hôpital Avicenne AP-HP, Bobigny, France; 4 Centre de Recherche Thérapeutique en Ophtalmologie, Université Paris-Descartes, Paris; 5 ULB-IBMM, Gosselies, Belgium; and 6 ...
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... Odile Jacob, 2539 Gerard M, Abitbol M, Delezoide AL,Duffer JL, Mallet J, Vekemans M (1995)PAX-genes expression during humanembryonic development, a preliminaryreport, l,: Comptes rendus de l'Acad6-mie des sciences, Paris 318,... more
... Odile Jacob, 2539 Gerard M, Abitbol M, Delezoide AL,Duffer JL, Mallet J, Vekemans M (1995)PAX-genes expression during humanembryonic development, a preliminaryreport, l,: Comptes rendus de l'Acad6-mie des sciences, Paris 318, 57-6610 Abitbol M, Menini C, Delezoide ...
Research Interests: Philosophy, Ethics, Epistemology, Technology, Biological Sciences, and 2 moreCase History and Embryos(Case History and Embryos)
(Case History and Embryos)
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ABSTRACT
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Atherosclerosis Gordon Research Conference Understanding the Pathophysiology and Identifying New Modes of Prevention Dates June 19-24, 2011 Location Salve Regina University Newport, RI Organizers Chairs: Jonathan D. Smith, John M. Chapman & Edward A. Fisher Vice Chair: Elaine W. Raines THE SRBI K...more
Six new born presenting an acquired nystagmus, associated with rhythmic head movements, have been explored clinically, electrophysiologically and neuroradiologically. Etiopathogenic hypotheses and experimental models are proposed. A... more
Six new born presenting an acquired nystagmus, associated with rhythmic head movements, have been explored clinically, electrophysiologically and neuroradiologically. Etiopathogenic hypotheses and experimental models are proposed. A twenty last years literature review is mentioned. It seemed interesting to authors to practice head scanners to find an organic lesion. The ethnic incidence is not negligible.
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Research Interests: Vision()
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The retina is highly exposed to oxidative stress due to the high level of oxygen consumption in this tissue and its exposure to light. The main DNA base lesion generated by oxygen free radicals is 8-oxoguanine (8-oxoG). However, its... more
The retina is highly exposed to oxidative stress due to the high level of oxygen consumption in this tissue and its exposure to light. The main DNA base lesion generated by oxygen free radicals is 8-oxoguanine (8-oxoG). However, its presence in retinal cells and the mechanisms underlying its repair remain undetermined. 8-oxoguanine DNA glycosylase (Ogg1) gene expression and messenger localization in adult mouse ocular tissues was analyzed by RT-PCR and in situ hybridization. Using immunohistochemistry, we determined the localization of Ogg1 protein and three base excision repair (BER) enzymes: apurinic/apyrimidic endonuclease (APE1), DNA polymerase beta, and X-ray repair cross-complementation group 1 (XRCC1). Ogg1 and AP-lyase activities in the neuroretina were obtained using double-stranded oligonucleotides harboring either an 8-oxoG residue or a tetrahydrofuran. We report here that 8-oxoG is abundant in the retina. Ogg1, the enzyme responsible for the recognition and excision of t...
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In situ hybridization of nucleic acid probes, encoding the key enzymes of the synthesis of neurotransmitters, with sections of retina is a new method giving complementary informations to the data obtained by immunocytochemistry and... more
In situ hybridization of nucleic acid probes, encoding the key enzymes of the synthesis of neurotransmitters, with sections of retina is a new method giving complementary informations to the data obtained by immunocytochemistry and autoradiography. It will allow a better characterization of amacrin cells, whatever might be their type, and a refined understanding of their function. It is an accurate tool to investigate the mechanisms of retinal degenerations and spontaneous or experimental microphtalmia.
Research Interests: Methods, Brain, Animals, Nucleic acid hybridization, Male, and 3 moreRetina, Rats, and Brain Chemistry
Research Interests: Biological Sciences, Humans, Mutation, Eye, Ear, and 2 moreOptic Disk and Organogenesis(Optic Disk and Organogenesis)
(Optic Disk and Organogenesis)
Research Interests: Genetics, Human Genetics, Complementary and Alternative Medicine, Membrane Proteins, Macular Degeneration, and 20 moreHumans, Metabolic diseases, Mutation, Retinitis pigmentosa, G protein-coupled receptors, Male, Neurofibromatosis, Proteins, Adult, Uroporphyrinogen Decarboxylase, Choroideremia, Codon, Base Sequence, Hematologic Diseases, Amino Acid Substitution Rates, Retinal Diseases, Protein Tyrosine Phosphatases, Syndrome, Parkinson Disease, and Guanylate Cyclase(Humans, Metabolic diseases, Mutation, Retinitis pigmentosa, G protein-coupled receptors, Male, Neurofibromatosis, Proteins, Adult, Uroporphyrinogen Decarboxylase, Choroideremia, Codon, Base Sequence, Hematologic Diseases, Amino Acid Substitution Rates, Retinal Diseases, Protein Tyrosine Phosphatases, Syndrome, Parkinson Disease, and Guanylate Cyclase)
(Humans, Metabolic diseases, Mutation, Retinitis pigmentosa, G protein-coupled receptors, Male, Neurofibromatosis, Proteins, Adult, Uroporphyrinogen Decarboxylase, Choroideremia, Codon, Base Sequence, Hematologic Diseases, Amino Acid Substitution Rates, Retinal Diseases, Protein Tyrosine Phosphatases, Syndrome, Parkinson Disease, and Guanylate Cyclase)
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Mutations of the gene encoding rhodopsin are responsible for 30% of the cases autosomal dominant retinitis pigmentosa. Rhodopsin molecules are key G-coupled transmembrane proteins initiating the visual transduction cascade in rods. These... more
Mutations of the gene encoding rhodopsin are responsible for 30% of the cases autosomal dominant retinitis pigmentosa. Rhodopsin molecules are key G-coupled transmembrane proteins initiating the visual transduction cascade in rods. These cells are specialized retinal cells allowing the detection of low intensity lights. Mutations in the rhodopsin gene lead to the progressive destruction of rods, clinically translated by night blindness, a progressive bilateral loss of the peripheral visual field, and predominant alterations of the rod component of the electroretinograms. Inherited colour vision deficiencies are mainly caused by alterations of the genes encoding coloured opsins. These proteins are G-coupled receptors specialized in visual transduction in the cones. These sensorial cells are localized in the center of the neural retina where they allow the detection of refined details and chromatic lights. Rearrangements of the genes encoding the green and the red color pigments are r...
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Research Interests: Genetics()
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The aim of this study was to determine the regional distribution in situ of the mRNA for the alpha 7 subunit of the neuronal nicotinic acetylcholine receptor in human fetal brain. We found high levels of alpha 7 gene expression in nuclei... more
The aim of this study was to determine the regional distribution in situ of the mRNA for the alpha 7 subunit of the neuronal nicotinic acetylcholine receptor in human fetal brain. We found high levels of alpha 7 gene expression in nuclei that receive sensory information, such as those of the neocortex and hippocampus, the thalamic nuclei, the reticular thalamic nucleus, the pontine nuclei and the superior olive complex. These data support a possible regulatory function for alpha 7-containing receptors in sensory processing, which may be involved in the pathological physiology of schizophrenia and autism. Early alpha 7 gene expression is also consistent with a morphogenetic role for alpha 7 receptors in central nervous system development.
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ABSTRACT Purpose Monogenic diseases until recently appeared simple from a molecular genetics point of view but correlations between genotypes and phenotypes still remain difficult to establish in many diseases and for many genes. For... more
ABSTRACT Purpose Monogenic diseases until recently appeared simple from a molecular genetics point of view but correlations between genotypes and phenotypes still remain difficult to establish in many diseases and for many genes. For autosomal dominant diseases such as Best Vitelliform Macular Dystrophy, supposed to be a juvenile disease, it appears that mutations of BEST1 gene can cause multiple phenotypes including early onset and late onset phenotypes as well as unexpected phenotypes such as RP. We report several novel mutations and their associated phenotypes and describe phenotypes linked to previously reoported mutations for which the phenotype had not been describe at all previously. The role of SOX9, MITF and OTX2 in the incomplete penetrance and the variable expressivity of BVMDs is duscussed as well the potential roles of SNPs occuring in coding exonsMethods We used genomic PCR with appropriate primers flanking all the exons of the BEST1 gene in order to amplify them. This Genomic PCR was followed by automated sequencing and careful analysis of the sequences obtained.Results We report the case of an unusual family where the Mother II2 of the proband III1, his maternal aunt II3, his brother III3 and his first cousin IIIIV, the son of his maternal aunt, carry a missense mutatation causing apparently only electrophysiological abnormalities. The Father II1 of the proband III1 turned out to carry a stop codon instead of the fifth normal BEST1 codon. The father did not display any electrophysiological nor any clinical abnormality and has a perfect monocular and binocular vision. In contrast the proband III1 carries both mutations with a severe phenotype.Conclusion This report exemplifies the necessity to study all family members in the case of BVMDs.
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La plupart des modèles animaux d’ischémie-reperfusion rétinienne qui ont été mis au point reposent sur l’injection de soluté isotonique dans la chamber antérieure de l’œil ou sur l’occlusion simultanée du nerf optique et des vaisseaux... more
La plupart des modèles animaux d’ischémie-reperfusion rétinienne qui ont été mis au point reposent sur l’injection de soluté isotonique dans la chamber antérieure de l’œil ou sur l’occlusion simultanée du nerf optique et des vaisseaux centraux rétiniens situés au cœur du nerf optique (artère et veine centrale de la rétine). Nous avons mis au point un nouveau modèle occlusion vasculaire unilatérale des vaisseaux rétiniens sans atteinte concomitante d’origine mécanique des axones des cellules ganglionnaires de la rétine.Par occlusion unilatérale de l’artère carotide externe et occlusion transitoire de l’artère ptérygopalatine ipsilalatérale, il s’est avéré possible chez la souris adulte (Souris avec amaurose Unilatérale (n = 40) et souris Sham (n = 40) d’éviter la reperfusion d’origine controlatérale et d’obtenir une amaurose unilatérale d’origine purement vasculaire. Il est possible de varier la durée d’ischémie et d’étudier le décours de la reperfusion rétinienne par diverses methods : électrorétinographie et angiographie in vivo puis après injection de fluorescéine intracardiaque et réalisation de rétines montées à plat par des méthods immunohistochimiques, par des méthodes d’étude de l’apoptose et surtout par RTPCR quantitative de certains ARNm, clés des diverses phases de la reperfusion. C’est ainsi qu’ont été étudiés des gènes d’expression précoce tels que Zif268, Arc, Jun, les gènes codant de très nombreux récepteurs au glutamate et des gènes impliqués dans la neurogénèse. Les temps étudiés ont été 4 heures, 24 heures, 72 heures, 7 jours et 1 mois avec 8 animaux groupe.Nous avons pu valider ce modèle comme modèle d’ischémie-reperfusion oculaire tant chez la souris que chez le rat. Des variations d’expression géniques ont pu être rattachées à chacun des stades étudiés. Par exemple celles des gènes COX2, GADD34, HSP70, PAI1.Nous avons mis au point le premier véritable modèle permettant d’étudier l’ischémie-reperfusion rétinienne sans interférences de facteurs mécaniques ou autres. Ce modèle se prête tout particulièrement aux tests précliniques des modulateurs des récepteurs aux glutamates (NMDA, Métabotropiques, AMPA, Kaïnate). Le glutamate joue en effet un rôle fondamenteur de neurotransmetteur dans les synapses des circuits rétiniens d’une part et dans les phénomènes liés à l’excitotoxicité. Ce modèle permettra d’étudier de nouvelles thérapies sur des souris KO, Knock in ou transgéniques atteintes d’hypertension artérielles et/ou d’athérosclérose situation fréquente retrouvée chez les sujets âgés. La thrombolyse peut s’accompagner d’excitotoxicité qui limite ses bénéfices. Ce modèle arrive donc au bon moment pour permettre des avancées thérapeutiques.Les accidents vasculaires oculaires s’accompagnent trop souvent encore d’échecs thérapeutiques du fait du caractère souvent trop tardif de l’examen des patients dû à la méconnaissance ou à l’incompréhension des symptômes ou malaises qu’ils ressentent. Ce modèle devrait permettre de mieux appréhender le potentiel thérapeutique des cellules souches de la rétine stimulées par l’ischémie.
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Les microphtalmies s’accompagnent le plus souvent d’un défaut de développement osseux orbitaire : c’est un micro-orbitisme, associé à un défaut de développement du sac conjonctival et des paupières pouvant aller jusqu’à une... more
Les microphtalmies s’accompagnent le plus souvent d’un défaut de développement osseux orbitaire : c’est un micro-orbitisme, associé à un défaut de développement du sac conjonctival et des paupières pouvant aller jusqu’à une micro-blépharite et même à un défaut de croissance du tiers moyen de la face entraînant un préjudice esthétique majeur. L’œil microphtalme présente également une enophtalmie que nous dénommons : micro-énophtalmie. De la même manière, les anophtalmies congénitales ou post énucléations d’autant plus qu’elles sont précoces et suivies d’une radiothérapie qui affecte le développement osseux mènent à un défaut de croissance orbito-palpébro-faciale marqué.Nous faisons une mise au point sur la prise en charge moderne des enfants atteints d’anophtalmies congénitales et microphtalmies extrêmes non voyantes, puis présentons un nouveau traitement chirurgical des microphtalmies voyantes. Cette situation est extrêmement fréquente en ophtalmo-pédiatrie. La microphtalmie est modérée, l’orbite et les paupières sont assez développées et c’est la micro-énophtalmie qui est la plus visible avec une fente palpébrale peu ouverte. Le traitement de choix est, selon nous, l’augmentation du volume du contenu intra orbitaire par greffes osseuses rétro-équatoriales. Elles sont réalisées à partir de 2 ans 1/2. Nous vous présentons les résultats de cette nouvelle technique sur une série de 12 enfants avec un recul de 2 ans.Nous avons eu d’excellents résultats avec une amélioration nette de l’aspect esthétique sur l’enophtalmie ainsi que sur le champ visuel et l’acuité visuelle. En cas de taille vraiment réduite de la cornée et de l’iris on propose une lentille souple colorée cosmétique à l’adolescence.Cette chirurgie apporte une amélioration aux microphtalmies voyantes, de plus les greffes osseuses croissent avec l’enfant et permettent un bénéfice de croissance orbito-palpébrale. Elles peuvent également être proposées à l’adolescent insuffisamment traité présentant une micro-énophtalmie modérée avec développement orbitaire harmonieux.
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To evaluate functional and ultrastructural changes in the retina of scavenger receptor B1 (SR-BI) knockout (KO) mice consuming a high fat cholate (HFC) diet. Three-month-old male KO and wild-type (WT) mice were fed an HFC diet for 30... more
To evaluate functional and ultrastructural changes in the retina of scavenger receptor B1 (SR-BI) knockout (KO) mice consuming a high fat cholate (HFC) diet. Three-month-old male KO and wild-type (WT) mice were fed an HFC diet for 30 weeks. After diet supplementation, plasma cholesterol levels and electroretinograms were analyzed. Neutral lipids were detected with oil red O, and immunohistochemistry was performed on cryostat ocular tissue sections. The retina, Bruch's membrane (BM), retinal pigment epithelium (RPE), and choriocapillaris (CC) were analyzed by transmission electron microscopy. Using the WT for reference, ultrastructural changes were recorded in HFC-fed SR-BI KO mice, including lipid inclusions, a patchy disorganization of the photoreceptor outer segment (POS) and the outer nuclear layer (ONL), and BM thickening with sparse sub-RPE deposits. Within the CC, there was abnormal disorganization of collagen fibers localized in ectopic sites with sparse and large vacuolization associated with infiltration of macrophages in the subretinal space, reflecting local inflammation. These lesions were associated with electroretinographic abnormalities, particularly increasing implicit time in a- and b-wave scotopic responses. Abnormal vascular endothelial growth factor (VEGF) staining was detected in the outer nuclear layer. HFC-fed SR-BI KO mice thus presented sub-RPE lipid-rich deposits and functional and morphologic alterations similar to some features observed in dry AMD. The findings lend further support to the hypothesis that atherosclerosis causes retinal and subretinal damage that increases susceptibility to some forms of AMD.
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Research Interests: Developmental Biology, Human Genetics, Skeletal muscle biology, Clinical and Molecular Human Genetics, Biological Sciences, and 13 moreCell line, Humans, Sequence alignment, Mutation, Female, Animals, Male, Human Molecular Genetics, Pedigree, Transforming Growth Factor Beta, Zebrafish, Amino Acid Sequence, and Molecular Sequence Data
AimsTo describe genetic and clinical findings in a French family affected by best vitelliform macular dystrophy (BVMD).MethodsWe screened eight at-risk members of a family, including a BVMD-affected proband, by direct sequencing of 11... more
AimsTo describe genetic and clinical findings in a French family affected by best vitelliform macular dystrophy (BVMD).MethodsWe screened eight at-risk members of a family, including a BVMD-affected proband, by direct sequencing of 11 bestrophin-1 (BEST1) exons. Individuals underwent ophthalmic examination and autofluorescent fundus imaging, indocyanine green angiography, electro-oculogram (EOG), electroretinogram (ERG), multifocal ERG, optical coherence tomography (OCT), and where possible, spectral domain OCT.ResultsThe sequence analysis of the BEST1 gene revealed one previously unknown mutation, c.15C>A (p.Y5X), in two family members and one recently described mutation, c.430A>G (p.S144G), in five family members. Fundus examination and electrophysiological responses provided no evidence of the disease in the patient carrying only the p.Y5X mutation. Three patients with the p.S144G mutation did not show any preclinical sign of BVMD except altered EOGs. Two individuals of the family exhibited a particularly severe phenotype of multifocal BVMD—one individual carrying the p.S144G mutation heterozygously and one individual harboring both BEST1 mutations (p.S144G inherited from his mother and p.Y5X from his father). Both of these family members had multifocal vitelliform autofluorescent lesions combined with abnormal EOG, and the spectral domain OCT displayed a serous retinal detachment. In addition, ERGs demonstrated widespread retinal degeneration and multifocal ERGs showed a reduction in the central retina function, which could be correlated with the decreased visual acuity and visual field scotomas.ConclusionsA thorough clinical evaluation found no pathological phenotype in the patient carrying the isolated p.Y5X mutation. The patients carrying the p.S144G variation in the protein exhibited considerable intrafamilial phenotypic variability. Two young affected patients in this family exhibited an early onset, severe, multifocal BVMD with a diffuse distribution of autofluorescent deposits throughout the retina and rapid evolution toward the loss of central vision. The other genetically affected relatives had only abnormal EOGs and displayed no or extremely slow electrophysiological evolution.