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1.
PLoS One ; 15(2): e0228622, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32040484

RESUMO

Optic nerve hypoplasia (ONH) is a congenital malformation with a reduced number of retinal ganglion cell axons in a thin optic nerve. It is a common cause of visual impairment in children and ONH is associated with neurodevelopmental disorders, pituitary hormone deficiencies, and brain malformations. In most cases, the aetiology is unknown, but both environmental factors and genetic causes have been described. This study aimed to identify genetic variants underlying ONH in a well-characterised cohort of individuals with ONH. We performed array comparative genomic hybridization and whole genome sequencing in 29 individuals with ONH. Rare variants were verified by Sanger sequencing and inheritance was assessed in parental samples. We identified 11 rare single nucleotide variants (SNVs) in ten individuals, including a homozygous variant in KIF7 (previously associated with Joubert syndrome), a heterozygous de novo variant in COL4A1 (previously described in an individual with porencephaly), and a homozygous variant in COL4A2. In addition, one individual harboured a heterozygous variant in OPA1 and a heterozygous variant in COL4A1, both were inherited and assessed as variants of unknown clinical significance. Finally, a heterozygous deletion of 341 kb involving exons 7-18 of SOX5 (associated with Lamb-Schaffer syndrome) was identified in one individual. The overall diagnostic yield of pathogenic or likely pathogenic variants in individuals with ONH using whole genome sequencing was 4/29 (14%). Our results show that there is a genetic heterogeneity in ONH and indicate that genetic causes of ONH are not rare. We conclude that genetic testing is valuable in a substantial proportion of the individuals with ONH, especially in cases with non-isolated ONH.


Assuntos
Heterogeneidade Genética , Hipoplasia do Nervo Óptico/genética , Nervo Óptico/patologia , Adolescente , Adulto , Criança , Hibridização Genômica Comparativa , Estudos Transversais , Éxons , Feminino , Testes Genéticos , Genoma Humano , Heterozigoto , Humanos , Masculino , Nervo Óptico/diagnóstico por imagem , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Células Ganglionares da Retina/patologia , Fatores de Transcrição SOXD/genética , Suécia/epidemiologia , Sequenciamento Completo do Genoma , Adulto Jovem
2.
J Craniofac Surg ; 31(1): e101-e103, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31688258

RESUMO

In this study, we present 2 patients, including 1 pediatric patient, with orbital tumors in the deep superonasal intraconal space, which were approached with upper fornix technique combined with a superior lateral cantholysis. The first patient was a 1-year-old girl who had presented with left upper eyelid retraction since the age of 2 months. Imaging studies revealed an orbital mass in the left postero-superonasal intraconal space. The second patient was a 71-year-old man who complained of decreased vision after cataract surgery in the left eye. Imaging studies revealed an orbital mass in the left superonasal intraconal space surrounding the optic nerve in the posterior orbit. In both the patients, incisional biopsy of the orbital mass with upper fornix approach was performed under general anesthesia. The diagnoses of congenital upper eyelid retraction caused by fibrosis in patient #1 and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in patient #2 were made, after pathological examinations. No significant intra- or postoperative complications occurred during a follow-up period of 10 months and 2 months, respectively.


Assuntos
Neoplasias Orbitárias/cirurgia , Idoso , Biópsia , Feminino , Humanos , Lactente , Masculino , Nervo Óptico/patologia , Neoplasias Orbitárias/diagnóstico por imagem
3.
World Neurosurg ; 133: 413-415, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31336173

RESUMO

A 71-year-old woman presented to our institution with a 2-week history of concentric bilateral left accentuated visual field loss. Examination of her eyes including funduscopy was normal. A gadolinium-enhanced magnetic resonance tomography showed contrast enhancement of the optic pathway in the T1-weighted sequence that included both optic nerves, the optic chiasm, and the left optic tract. Differential diagnoses of this kind of lesion extending along the optic nerves include neurosarcoidosis, lymphoma, and glioma. The patient was treated with high-dose corticosteroids under the suspicion of neurosarcoidosis. During that time her vision deteriorated, resulting in amaurosis on her left eye and marginal peripheral vision on the right. A biopsy of the left optic nerve revealed a pilocytic astrocytoma, which to some extent contrasted the observed clinical course. After discussing the treatment options including radiotherapy and chemotherapy, the patient opted for supportive care and died 3 months later.


Assuntos
Astrocitoma/diagnóstico , Neoplasias do Nervo Óptico/diagnóstico , Nervo Óptico/patologia , Idoso , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia , Feminino , Humanos , Imagem por Ressonância Magnética , Nervo Óptico/diagnóstico por imagem , Neoplasias do Nervo Óptico/diagnóstico por imagem , Neoplasias do Nervo Óptico/patologia
4.
Pediatr Blood Cancer ; 67(1): e27998, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571399

RESUMO

BACKGROUND: Retinoblastoma with macroscopic optic nerve (ON) invasion depicted by imaging at diagnosis remains a major problem and carries a poor prognosis. We sought to describe the treatment and outcome of these high-risk patients. METHODS: Retrospective mono-institutional clinical, radiological, and histological review of patients with uni- or bilateral retinoblastoma with obvious ON invasion, defined by radiological optic nerve enlargement (RONE) depicted by computed tomography scan or magnetic resonance imaging (MRI), was performed. RESULTS: Between 1997 and 2014, among the 936 patients with retinoblastoma treated at Institut Curie, 11 had detectable RONE. Retinoblastoma was unilateral in 10 and bilateral in one. Median age at diagnosis was 28 months (range, 11-96). ON enlargement extended to the orbital portion in three patients, to the optic canal in five, to the prechiasmatic portion in two, and to the optic chiasm in one. Nine patients received neoadjuvant chemotherapy and partial response was obtained in all. Enucleation was performed in 10/11 patients-by an anterior approach in three and by anterior and subfrontal approaches in seven. Three patients had a positive ON resection margin (2/3 after primary enucleation). All enucleated patients received adjuvant treatment (conventional chemotherapy: 10, high-dose chemotherapy: seven, radiotherapy: five). Leptomeningeal progression occurred in four patients. Seven are in first complete remission (median follow up: 8 years [3.5-19.4]). CONCLUSION: Neoadjuvant chemotherapy and microscopic complete resection have a pivotal role in the management of retinoblastoma with RONE. MRI is recommended for initial and pre-operative accurate staging. Surgery should be performed by neurosurgeons in case of posterior nerve invasion. Radiotherapy is required in case of incomplete resection.


Assuntos
Neoplasias do Nervo Óptico/patologia , Nervo Óptico/patologia , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Lactente , Imagem por Ressonância Magnética/métodos , Masculino , Invasividade Neoplásica , Neoplasias do Nervo Óptico/diagnóstico por imagem , Neoplasias do Nervo Óptico/terapia , Prognóstico , Neoplasias da Retina/diagnóstico por imagem , Neoplasias da Retina/terapia , Retinoblastoma/diagnóstico por imagem , Retinoblastoma/terapia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
5.
J Pediatr Ophthalmol Strabismus ; 56: e68-e72, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31821510

RESUMO

Differentiating true optic nerve edema from pseudo-optic nerve edema is a diagnostic dilemma faced by pediatric ophthalmologists. This case series suggests that oral fluorescein angiography is equivalent to intravenous fluorescein angiography in making this distinction. [J Pediatr Ophthalmol Strabismus. 2019;56:e68-e72.].


Assuntos
Angiofluoresceinografia/métodos , Verde de Indocianina/administração & dosagem , Drusas do Disco Óptico/diagnóstico , Nervo Óptico/patologia , Administração Oral , Adolescente , Criança , Corantes/administração & dosagem , Feminino , Fundo de Olho , Humanos , Injeções Intravenosas , Masculino
6.
J BUON ; 24(5): 2168-2172, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31786891

RESUMO

PURPOSE: Farnesol has been shown to exhibit important anticancer potential. However, its antiproliferative effects have not been examined against the optic nerve sheath meningioma cells. In this study the potential of Farnesol in the treatment of optic nerve meningioma was evaluated by examining its antiproliferative effects against the HBL-52 cells. METHODS: The MTT assay was used to determine cell viability of HBL-52 cells. Autophagy was detected by transfection assay. The cell migration and invasion of HBL-52 cells was determined by transwell assay. Protein expression was checked by western blot assay. RESULTS: The results showed that Farnesol decreased significantly the viability of HBL-52 cells and showed an IC50 of 25 µM. The antiproliferative effects were due to the activation of the autophagy in the HBL-52 cells. The autophagy was also accompanied by upsurge of LC3 II and Beclin 1 expression. Farnesol also triggered the cell cycle arrest of the HBL-52 at the G2/M phase of the cell cycle which was accompanied by suppression of cyclin B1. The cell migration and invasion of the HBL-52 cells was also suppressed by Farnesol via inhibition of MMP-2 and 9 expressions. CONCLUSIONS: To sum up, Farnesol may prove beneficial in the treatment of optic nerve sheath meningioma as it has shown significant antiproliferative effects against this rare form of tumor.


Assuntos
Proliferação de Células/efeitos dos fármacos , Farneseno Álcool/farmacologia , Meningioma/tratamento farmacológico , Neoplasias do Nervo Óptico/tratamento farmacológico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Meningioma/genética , Meningioma/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/patologia , Neoplasias do Nervo Óptico/genética , Neoplasias do Nervo Óptico/patologia , Transdução de Sinais/efeitos dos fármacos
7.
Ideggyogy Sz ; 72(11-12): 427-431, 2019 Nov 30.
Artigo em Húngaro | MEDLINE | ID: mdl-31834687

RESUMO

Among tumours found in the suprasellar region metastases are very rare and the most frequent primary tumours are lung and breast cancer. Data of a patient with clear cell renal carcinoma with intra-suprasellar metastasis will be discussed. As in most of the tumours in the sellar region, the first symptom was visual deterioration with visual field defect. A transsphenoidal debulking of the tumour was performed and the residual tumor was treated by CyberKnife hypofractionated stereotactic radiotherapy. Both our patient's visual acuity and visual field impairment improved after the surgery and CyberKnife treatment. At 6-month after irradiation, MR of the sella showed a complete remission of the tumour. This was the first treatment with CyberKnife in our country in case of a tumour close to the optic chiasm. According to our best knowledge, there are 21 cases in the literature with renal cell carcinoma metastasis in the suprasellar region.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Nervo Óptico/cirurgia , Radiocirurgia/métodos , Sela Túrcica/cirurgia , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Metástase Neoplásica , Nervo Óptico/patologia , Neoplasias Hipofisárias , Radiocirurgia/instrumentação , Resultado do Tratamento , Transtornos da Visão/etiologia
8.
Tunis Med ; 97(7): 925-928, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31872405

RESUMO

Optic nerve infiltration is relatively rare in acute lymphoblastic leukemia. We present a case of a -53 year-old-man who was diagnosed with T- acute lymphoblastic leukemia (ALL). The patient was treated with ALL national protocol and the central nervous system (CNS) prophylactic management. On treatment, the patient presented with sudden severe vision deterioration of both eyes. Fundoscopic examination of the eye and magnetic resonance imaging of the orbits were in favor of an infiltration of the optical nerve. An isolated extramedullary relapse of the optical nerve was retained. The patient was treated with salvage chemotherapy systematic and intrathecal. Waiting forthe beginning of radiotherapy, the patient presented a bone marrow relapse. He died of a severe hemorrhagic syndrome. Conclusion: Optic nerve leukemic infiltration has a severe prognosis. Ophthalmic assessment is essential in patients with ALL in order to diagnose an early ocular involvement and the patient's vision can be preserved if treatment is initiated promptly.


Assuntos
Infiltração Leucêmica/diagnóstico , Nervo Óptico/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Antineoplásicos/administração & dosagem , Evolução Fatal , Humanos , Infiltração Leucêmica/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Terapia de Salvação/métodos
9.
J Comp Pathol ; 172: 107-109, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31690407

RESUMO

A juvenile female Moroccan uromastyx (Uromastyx acanthinurus nigriventris) that died unexpectedly was necropsied. Necropsy examination revealed minimal intracoelomic fat, small numbers of intestinal nematodes and intraocular masses within the vitreous chamber of both eyes. One of the intraocular masses was focally contiguous with the optic nerve and composed of neuroparenchyma with rare glial cells, consistent with a diagnosis of neural heterotopia. This condition is considered a neuroectodermal malformation, readily recognized in human medicine but rarely reported in animals. To the authors' knowledge, this is the first case of intraocular neural heterotopia reported in a reptile.


Assuntos
Coristoma/veterinária , Lagartos , Malformações do Sistema Nervoso/veterinária , Nervo Óptico/patologia , Animais , Olho/patologia , Feminino , Placa Neural/crescimento & desenvolvimento , Placa Neural/patologia
10.
Tunis Med ; 97(3): 504-507, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31729727

RESUMO

INTRODUCTION: Ocular infiltration of leukemia can involve orbit, uveal tract, retina and optic nerve. It may result from direct ocular infiltration by leukemic cells or indirect ocular involvement resulting from secondary hematologic changes, opportunistic infections and complications of various modalities of therapy. We report a case of unilateral infiltration of the optic nerve revealing a relapse of acute lymphoblastic leukemia. CASE REPORT: forty eight years-old woman in a remission of acute B lymphoblastic leukemia presented with headaches and blurred vision in the left eye. Ophthalmic examination showed a visual acuity reduced to 20/200 in the left eye, and a voluminous disc edema with papillary mass surrounded by retinal hemorrhages, exudates and important serous retinal detachment. CT scan showed a thickened left optic nerve and excluded true papillary edema due to intracranial hypertension secondary to central nervous system involvement. Myelogram and lumbar punction demonstrated blast infiltration and confirmed ocular relapse of the leukemia. CONCLUSION: The incidence of ocular involvement lymphoblastic acute leukemias decreased since the introduction of a systematic prophylactic treatment of central nervous system. Periodic ophthalmic examination is necessary to allow early diagnosis and treatment.


Assuntos
Infiltração Leucêmica/diagnóstico , Nervo Óptico/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Diagnóstico Diferencial , Neoplasias Oculares/diagnóstico , Neoplasias Oculares/secundário , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva
11.
Invest Ophthalmol Vis Sci ; 60(14): 4896-4903, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31752019

RESUMO

Purpose: The geometry of retinal nerve fibers may be altered with myopia, a known risk factor for glaucoma. Recent developments in high resolution imaging have enabled direct visualization of nerve fiber bundles at the temporal raphe with clinical hardware, providing evidence that this area is sensitive to glaucomatous damage. Here, we test the hypothesis that nerve fiber geometry is altered by myopia, both at the temporal raphe and surrounding the optic nerve head. Methods: Seventy-eight healthy individuals participated, with refractive errors distributed between emmetropia and high myopia (+0 to -13 DS). Custom high-density OCT scans were used to visualize RFNL bundle trajectory at the temporal raphe. A standard clinical OCT protocol was used to assess papillary minimum rim width (MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness. Results: Measures of raphe shape-including position, orientation, and width-did not depend significantly on axial length. In 7.5% of subjects, the raphe was rotated sufficiently that inversion of structure-function mapping to visual field space is predicted in the nasal step region. Low concordance to ISNT and related rules was observed in myopia (e.g., for RNFL, 8% of high axial myopes compared with 67% of emmetropes). Greater robustness to refractive error was observed for the IT rule. Conclusions: High density OCT scans enabled visualization of marked interindividual variation in temporal raphe geometry; however, these variations were not well predicted by degree of myopia as represented by axial length. That said, degree of myopia was associated with abnormal thickness profiles for the papillary and peripapillary nerve fiber layer.


Assuntos
Comprimento Axial do Olho/patologia , Emetropia/fisiologia , Miopia/patologia , Fibras Nervosas/patologia , Nervo Óptico/patologia , Retina/patologia , Células Ganglionares da Retina/patologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Nervo Óptico/diagnóstico por imagem , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica , Campos Visuais , Adulto Jovem
12.
Oxid Med Cell Longev ; 2019: 8060962, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781352

RESUMO

Glaucoma is characterized by a progressive optic nerve degeneration and retinal ganglion cell loss, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role in glaucomatous neurodegeneration. Here, we investigate the impact of activation of cyclic adenosine 3',5'-monophosphate (cAMP)/protein kinase A (PKA) pathway on mitochondrial dynamics of ONH astrocytes exposed to oxidative stress. ONH astrocytes showed a significant loss of astrocytic processes in the glial lamina of glaucomatous DBA/2J mice, accompanied by basement membrane thickening and collagen deposition in blood vessels and axonal degeneration. Serial block-face scanning electron microscopy data analysis demonstrated that numbers of total and branched mitochondria were significantly increased in ONH astrocytes, while mitochondrial length and volume density were significantly decreased. We found that hydrogen peroxide- (H2O2-) induced oxidative stress compromised not only mitochondrial bioenergetics by reducing the basal and maximal respiration but also balance of mitochondrial dynamics by decreasing dynamin-related protein 1 (Drp1) protein expression in rat ONH astrocytes. In contrast, elevated cAMP by dibutyryl-cAMP (dbcAMP) or isobutylmethylxanthine treatment significantly increased Drp1 protein expression in ONH astrocytes. Elevated cAMP exacerbated the impairment of mitochondrial dynamics and reduction of cell viability to oxidative stress in ONH astrocytes by decreasing optic atrophy type 1 (OPA1), and mitofusin (Mfn)1/2 protein expression. Following combined treatment with H2O2 and dbcAMP, PKA inhibition restored mitochondrial dynamics by increasing mitochondrial length and decreasing mitochondrial number, and this promoted cell viability in ONH astrocytes. Also, PKA inhibition significantly promoted Akt/Bax phosphorylation and Mfn1/2 oligomerization in ONH astrocytes. These results suggest that modulation of the cAMP/PKA signaling pathway may have therapeutic potential by activating Akt/Bax phosphorylation and promoting Mfn1/2 oligomerization in glaucomatous ONH astrocytes.


Assuntos
Astrócitos/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Glaucoma/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Nervo Óptico/metabolismo , Estresse Oxidativo , Multimerização Proteica , Transdução de Sinais , Proteína X Associada a bcl-2/metabolismo , Animais , Astrócitos/patologia , Feminino , Glaucoma/patologia , Camundongos , Nervo Óptico/patologia , Ratos , Ratos Sprague-Dawley
13.
J Pediatr Ophthalmol Strabismus ; 56: e57-e59, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31622478

RESUMO

Few anecdotal reports have documented new onset and progression of myelination of the retinal nerve fiber layer. The authors report the unusual onset and progression of acquired myelination of the retinal nerve fiber layer in two children, following the diagnosis of presumed idiopathic intracranial hypertension. The nosologic relationship between myelination of the retinal nerve fiber layer and idiopathic intracranial hypertension is unclear and requires elucidation by further studies. [J Pediatr Ophthalmol Strabismus. 2019;56:e57-e59.].


Assuntos
Fibras Nervosas Mielinizadas/patologia , Pseudotumor Cerebral/complicações , Doenças Retinianas/diagnóstico , Células Ganglionares da Retina/patologia , Criança , Humanos , Lactente , Masculino , Nervo Óptico/patologia , Pseudotumor Cerebral/diagnóstico , Doenças Retinianas/etiologia , Tomografia de Coerência Óptica
14.
Nat Commun ; 10(1): 4794, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641127

RESUMO

Central nervous system myelin is a multilayered membrane produced by oligodendrocytes to increase neural processing speed and efficiency, but the molecular mechanisms underlying axonal selection and myelin wrapping are unknown. Here, using combined morphological and molecular analyses in mice and zebrafish, we show that adhesion molecules of the paranodal and the internodal segment work synergistically using overlapping functions to regulate axonal interaction and myelin wrapping. In the absence of these adhesive systems, axonal recognition by myelin is impaired with myelin growing on top of previously myelinated fibers, around neuronal cell bodies and above nodes of Ranvier. In addition, myelin wrapping is disturbed with the leading edge moving away from the axon and in between previously formed layers. These data show how two adhesive systems function together to guide axonal ensheathment and myelin wrapping, and provide a mechanistic understanding of how the spatial organization of myelin is achieved.


Assuntos
Axônios/fisiologia , Sistema Nervoso Central/fisiologia , Bainha de Mielina/fisiologia , Moléculas de Adesão de Célula Nervosa/metabolismo , Animais , Animais Geneticamente Modificados , Adesão Celular/fisiologia , Moléculas de Adesão Celular Neuronais/genética , Moléculas de Adesão Celular Neuronais/metabolismo , Contactina 1/genética , Contactina 1/metabolismo , Feminino , Larva , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Bainha de Mielina/patologia , Glicoproteína Associada a Mielina/genética , Glicoproteína Associada a Mielina/metabolismo , Moléculas de Adesão de Célula Nervosa/genética , Nervo Óptico/metabolismo , Nervo Óptico/patologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
15.
G3 (Bethesda) ; 9(12): 3953-3959, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31575636

RESUMO

Time-course high-throughput assays of gene expression and enhancer usage in zebrafish provide a valuable characterization of the dynamic mechanisms governing gene regulatory programs during CNS axon regeneration. To facilitate the exploration and functional interpretation of a set of fully-processed data on regeneration-associated temporal transcription networks, we have created an interactive web application called Regeneration Rosetta Using either built-in or user-provided lists of genes in one of dozens of supported organisms, our web application facilitates the (1) visualization of clustered temporal expression trends; (2) identification of proximal and distal regions of accessible chromatin to expedite downstream motif analysis; and (3) description of enriched functional gene ontology categories. By enabling a straightforward interrogation of these rich data without extensive bioinformatic expertise, Regeneration Rosetta is broadly useful for both a deep investigation of time-dependent regulation during regeneration in zebrafish and hypothesis generation in other organisms.


Assuntos
Cromatina/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Internet , Regeneração Nervosa/genética , Software , Animais , Evolução Biológica , Colesterol/metabolismo , Genoma , Lipídeos/biossíntese , Nervo Óptico/patologia , Nervo Óptico/fisiopatologia , Peixe-Zebra/genética
16.
Artigo em Russo | MEDLINE | ID: mdl-31577273

RESUMO

The infraoptic anterior cerebral artery (ACA) is an abnormal vessel that usually is a bifurcation of the intradural part of the internal carotid artery (ICA) or near the site of discharge of the ophthalmic artery, which passes under the ipsilateral optic nerve and penetrates between the optic nerves into the prechiasm cistern, reaching the ACA-AcomA complex. The infra-optic ACA is an extremely rare anomaly, but it may be of great clinical significance in surgery of the arteries of the anterior sections of the Willis circle. The article describes the case of a combination of infra-optical ACA with an aneurysm of the ACA-AcomA complex. This observation is of interest both from the viewpoint of the rarity of the considered pathology and the associated increased risk of the formation of intracranial aneurysms.


Assuntos
Artéria Cerebral Anterior , Aneurisma Intracraniano , Artéria Cerebral Anterior/diagnóstico por imagem , Artéria Cerebral Anterior/cirurgia , Artéria Carótida Interna , Círculo Arterial do Cérebro , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Nervo Óptico/patologia
17.
Exp Neurol ; 322: 113063, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31518568

RESUMO

Visual deficits after traumatic brain injury (TBI) are common, but interventions that limit the post-trauma impairments have not been identified. We have found that treatment with the cannabinoid type-2 receptor (CB2) inverse agonist SMM-189 for 2 weeks after closed-head blast TBI greatly attenuates the visual deficits and retinal pathology this otherwise produces in mice, by modulating the deleterious role of microglia in the injury process after trauma. SMM-189, however, has not yet been approved for human use. Raloxifene is an FDA-approved estrogen receptor drug that is used to treat osteoporosis, but it was recently found to also show noteworthy CB2 inverse agonism. In the current studies, we found that a high pressure air blast in the absence of raloxifene treatment yields deficits in visual acuity and contrast sensitivity, reductions in the A-wave and B-wave of the scotopic electroretinogram (ERG), light aversion, and increased pupil constriction to light. Raloxifene delivered daily for two weeks after blast at 5-10 mg/kg mitigates or eliminates these abnormalities (with the higher dose generally more effective). This functional rescue with raloxifene is accompanied by a biasing of microglia from the harmful M1 to the helpful M2 state, and reductions in retinal, optic nerve, and oculomotor nucleus pathology. We also found that raloxifene treatment is still effective even when delayed until 48 h after TBI, and that raloxifene benefit appears attributable to its CB2 inverse agonism rather than its estrogenic actions. Our studies show raloxifene is effective in treating visual injury after brain and/or eye trauma, and they provide basis for phase-2 efficacy testing in human clinical trials.


Assuntos
Concussão Encefálica/complicações , Fármacos Neuroprotetores/farmacologia , Cloridrato de Raloxifeno/farmacologia , Receptor CB2 de Canabinoide/efeitos dos fármacos , Transtornos da Visão/etiologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/patologia , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/patologia , Receptor CB2 de Canabinoide/agonistas , Retina/patologia , Transtornos da Visão/patologia
18.
Med Sci Monit ; 25: 6911-6916, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31551404

RESUMO

BACKGROUND Epiduroscopy is commonly used for the evaluation and treatment of low back pain. Saline with or without local anesthetic addition was used to visualize epidural space structure during this procedure. A rapid increase in epidural space pressure is transmitted into the spinal space to the optic nerve sheath. This study aimed to estimate the effects of epiduroscopy on optic nerve sheath diameter (ONSD) according to the volume of fluid using the ultrasonographic measurement of optic nerve diameter in adult patients. MATERIAL AND METHODS Sixty patients who had been treated for low back pain with epiduroscopy using low-volume (LV) or high-volume (HV) fluid application were enrolled into the study. Measurement of ONSD was performed before (T0) and immediately after epiduroscopy (T1), at 10 min (T2), and 20 min (T3) after the epiduroscopy. RESULTS Both groups showed significant differences over time in ONSD (PGroup×Time=0.001). The HV group showed greater changes from T0 to T2 and T3 than the LV group in ONSD. However, in both groups, ONSDs at T2 and T3 were significantly larger than those with the highest values at T2 compared to T0. CONCLUSIONS Ultrasonography of ONSD presents a good level of diagnostic accuracy for identifying epidural hypertension. In the clinical decision-making phase, this may help physicians to be more cautious about volume when performing epidural injections to treat this disease.


Assuntos
Espaço Epidural/diagnóstico por imagem , Pressão Intracraniana/fisiologia , Nervo Óptico/diagnóstico por imagem , Adulto , Anestésicos Locais/administração & dosagem , China , Feminino , Humanos , Hipertensão Intracraniana/fisiopatologia , Laparoscopia/métodos , Dor Lombar/terapia , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Bainha de Mielina/patologia , Nervo Óptico/patologia , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Coluna Vertebral/cirurgia , Ultrassonografia
20.
Proc Natl Acad Sci U S A ; 116(33): 16507-16512, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31371497

RESUMO

The retina is an extension of the brain. Like the brain, neurodegeneration of the retina occurs with age and is the cause of several retinal diseases including optic neuritis, macular degeneration, and glaucoma. Liver X receptors (LXRs) are expressed in the brain where they play a key role in maintenance of cerebrospinal fluid and the health of dopaminergic neurons. Herein, we report that LXRs are expressed in the retina and optic nerve and that loss of LXRß, but not LXRα, leads to loss of ganglion cells in the retina. In the retina of LXRß-/- mice, there is an increase in amyloid A4 and deposition of beta-amyloid (Aß) aggregates but no change in the level of apoptosis or autophagy in the ganglion cells and no activation of microglia or astrocytes. However, in the optic nerve there is a loss of aquaporin 4 (AQP4) in astrocytes and an increase in activation of microglia. Since loss of AQP4 and microglial activation in the optic nerve precedes the loss of ganglion cells, and accumulation of Aß in the retina, the cause of the neuronal loss appears to be optic nerve degeneration. In patients with optic neuritis there are frequently AQP4 autoantibodies which block the function of AQP4. LXRß-/- mouse is another model of optic neuritis in which AQP4 antibodies are not detectable, but AQP4 function is lost because of reduction in its expression.


Assuntos
Receptores X do Fígado/deficiência , Degeneração Neural/patologia , Nervo Óptico/patologia , Retina/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Aquaporina 4/metabolismo , Astrócitos/metabolismo , Astrócitos/patologia , Feminino , Receptores X do Fígado/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Degeneração Neural/metabolismo , Neuroglia/metabolismo , Neuroglia/patologia , Oligodendroglia/metabolismo , Nervo Óptico/metabolismo , Retina/metabolismo , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia
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