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1.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806565

RESUMO

Congenital fibrosis of the extraocular muscles (CFEOM) is a congenital cranial dysinnervation disorder caused by developmental abnormalities affecting cranial nerves/nuclei innervating the extraocular muscles. Autosomal dominant CFEOM arises from heterozygous missense mutations of KIF21A or TUBB3. Although spatiotemporal expression studies have shown KIF21A and TUBB3 expression in developing retinal ganglion cells, it is unclear whether dysinnervation extends beyond the oculomotor system. We aimed to investigate whether dysinnervation extends to the visual system by performing high-resolution optical coherence tomography (OCT) scans characterizing retinal ganglion cells within the optic nerve head and retina. Sixteen patients with CFEOM were screened for mutations in KIF21A, TUBB3, and TUBB2B. Six patients had apparent optic nerve hypoplasia. OCT showed neuro-retinal rim loss. Disc diameter, rim width, rim area, and peripapillary nerve fiber layer thickness were significantly reduced in CFEOM patients compared to controls (p < 0.005). Situs inversus of retinal vessels was seen in five patients. Our study provides evidence of structural optic nerve and retinal changes in CFEOM. We show for the first time that there are widespread retinal changes beyond the retinal ganglion cells in patients with CFEOM. This study shows that the phenotype in CFEOM extends beyond the motor nerves.


Assuntos
Fibrose/patologia , Músculos Oculomotores/patologia , Oftalmoplegia/patologia , Nervo Óptico/patologia , Retina/patologia , Adulto , Nervos Cranianos/patologia , Feminino , Fibrose/genética , Humanos , Masculino , Mutação de Sentido Incorreto/genética , Oftalmoplegia/genética , Disco Óptico/patologia , Fenótipo , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Adulto Jovem
2.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33671012

RESUMO

The need for remyelinating drugs is essential for healing disabling diseases such as multiple sclerosis (MS). One of the reasons for the lack of this class of therapies is the impossibility to monitor remyelination in vivo, which is of utmost importance to perform effective clinical trials. Here, we show how optical coherence tomography (OCT), a cheap and non-invasive technique commonly used in ophthalmology, may be used to assess remyelination in vivo in MS patients. Our pioneer approach validates OCT as a technique to study remyelination of the optic nerve and reflects what is occurring in non-accessible central nervous system (CNS) structures, like the spinal cord. In this study we used the orally bioavailable small molecule VP3.15, confirming its therapeutical potential as a neuroprotective, anti-inflammatory, and probably remyelinating drug for MS. Altogether, our results confirm the usefulness of OCT to monitor the efficacy of remyelinating therapies in vivo and underscore the relevance of VP3.15 as a potential disease modifying drug for MS therapy.


Assuntos
Esclerose Múltipla/tratamento farmacológico , Nervo Óptico/efeitos dos fármacos , Remielinização , Bibliotecas de Moléculas Pequenas/farmacologia , Tomografia de Coerência Óptica/métodos , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Neuroproteção , Nervo Óptico/diagnóstico por imagem , Nervo Óptico/patologia
6.
PLoS One ; 16(1): e0243862, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33406093

RESUMO

ST266 is the biological secretome of cultured Amnion-derived Multipotent Progenitor cells containing multiple growth factors and cytokines. While intranasally-administered ST266 improves the phenotype in experimental optic neuritis, specific ST266 components mediating these effects are not known. We compared the effects of ST266 with and without removal of large molecular weight proteins both in vitro and in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice. Mice were treated daily with intranasal vehicle, ST266 or lower molecular weight fraction of ST266. Retinal ganglion cells were counted in isolated retinas, and optic nerves were assessed for inflammation and demyelination. ST266 treatment significantly improved retinal ganglion cell survival and reduced optic nerve demyelination in EAE mice. The lower molecular weight ST266 fraction significantly improved optic nerve demyelination, but only showed a trend towards improved retinal ganglion cell survival. ST266 fractions below 50kDa increased Schwann cell proliferation in vitro, but were less effective than non-fractionated ST266. Demyelination attenuation was partially associated with the lower molecular weight ST266 fraction, but removal of higher molecular weight biomolecules from ST266 diminishes its neuroprotective effects, suggesting at least some high molecular weight proteins play a role in ST266-mediated neuroprotection.


Assuntos
Âmnio/citologia , Células-Tronco Multipotentes/citologia , Neuroproteção , Animais , Proliferação de Células , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/patologia , Encefalomielite Autoimune Experimental/complicações , Encefalomielite Autoimune Experimental/patologia , Feminino , Camundongos Endogâmicos C57BL , Peso Molecular , Glicoproteína Mielina-Oligodendrócito , Nervo Óptico/patologia , Neurite Óptica/complicações , Neurite Óptica/patologia , Peptídeos , Células Ganglionares da Retina/patologia , Células de Schwann/patologia
7.
Int J Mol Sci ; 22(3)2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33499149

RESUMO

Gelsolin amyloidosis typically presents with corneal lattice dystrophy and is most frequently associated with pathogenic GSN variant p.Asp214Asn. Here we report clinical and histopathological features of gelsolin amyloidosis associated with a novel GSN variant p.Glu580Lys. We studied DNA samples of seven members of a two-generation family. Exome sequencing was performed in the proband, and targeted Sanger sequencing in the others. The heterozygous GSN variant p.Glu580Lys was identified in six patients. The patients exhibited corneal dystrophy (5/6), loose skin (5/6) and/or heart arrhythmia (3/6) and one presented with bilateral optic neuropathy. The impact of the mutation on the protein structure was evaluated in silico. The substitution is located in the fifth domain of gelsolin protein, homologous to the second domain harboring the most common pathogenic variant p.Asp214Asn. Structural investigation revealed that the mutation might affect protein folding. Histopathological analysis showed amyloid deposits in the skin. The p.Glu580Lys is associated with corneal dystrophy, strengthening the association of the fifth domain of gelsolin protein with the typical amyloidosis phenotype. Furthermore, optic neuropathy may be related to the disease and is essential to identify before discussing corneal transplantation.


Assuntos
Amiloidose Familiar/diagnóstico , Amiloidose Familiar/genética , Gelsolina/química , Gelsolina/genética , Mutação , Adulto , Idoso , Neuropatias Amiloides Familiares , Amiloidose , Doenças da Córnea , Distrofias Hereditárias da Córnea , Exoma , Saúde da Família , Feminino , Fundo de Olho , Estudos de Associação Genética , Ácido Glutâmico/química , Humanos , Lisina/química , Masculino , Pessoa de Meia-Idade , Nervo Óptico/patologia , Doenças do Nervo Óptico , Fenótipo , Dobramento de Proteína , Tomografia de Coerência Óptica
8.
BMJ Case Rep ; 14(1)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472799

RESUMO

We report the case of a 19-year-old patient with symptomatic unilateral serous maculopathy associated with an optic nerve coloboma. Fluorescein angiography detected a focal late leak at the temporal edge of the coloboma which was later found to correspond with an area of choroidal neovascularisation on optical coherence tomography angiography. A course of intravitreal ranibizumab achieved good clinical and structural response. This report contributes to the evidence that maculopathies associated with cavitary optic nerve anomalies may in some instances result from choroidal neovascularisation. It also highlights the importance of angiography to identify potential choroidal neovascular membranes, particularly in the absence of haemorrhages and neovascular membranes on fundus examination and conventional optical coherence tomography.


Assuntos
Coriorretinopatia Serosa Central/diagnóstico por imagem , Neovascularização de Coroide/diagnóstico por imagem , Coloboma/diagnóstico por imagem , Nervo Óptico/anormalidades , Inibidores da Angiogênese , Coriorretinopatia Serosa Central/complicações , Coriorretinopatia Serosa Central/tratamento farmacológico , Coriorretinopatia Serosa Central/patologia , Neovascularização de Coroide/complicações , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/patologia , Coloboma/complicações , Coloboma/patologia , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Nervo Óptico/diagnóstico por imagem , Nervo Óptico/patologia , Ranibizumab/uso terapêutico , Tomografia de Coerência Óptica , Resultado do Tratamento , Adulto Jovem
9.
Radiol Med ; 126(5): 698-706, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33392980

RESUMO

OBJECTIVE: Retinal nerve fiber layer thickness (RNFL) is a biomarker of neuroaxonal loss and index of visual function in multiple sclerosis (MS). We aimed to assess the correlation between radiomic features and RNFL, visual acuity (VA) at patients' presentation, visual outcome (VO), and clinical diagnosis. METHODS: We reviewed imaging and clinical data of 25 patients with a first episode of optic neuritis (ON) (14 females, 11 males; 5 bilateral ON; 7 left ON; 13 right ON). All patients underwent a complete ophthalmological assessment, including visual acuity and RNFL, neurological evaluation, orbits MRI. Segmentation of the optic nerves was performed through 3D slicer open software to get radiomics analysis. All patients underwent a complete neuro-ophthalmological follow-up at 6 months to assess the VO, classified as: complete recovery, partial recovery, deficit persistence/relapse, or visual worsening and were diagnosed as MS or clinically isolated syndrome. RESULTS: We observed significant correlations between radiomic features and RNFL and between radiomic features and VA. Regression model analysis identified 1 radiomic feature with significant association with VO (Gray Level non-uniformity Normalized, p = 0.004) and 6 radiomic features with significant correlation with diagnosis (High Gray Level Zone Emphasis, p < 0.001; Entropy, p < 0.001, for T1 segmentation; Mean Absolute Deviation, p < 0.001; Coarseness < 0.001; Small Area Low Gray Level Emphasis, p < 0.001; Contrast, p = 0.008, for STIR segmentation). CONCLUSION: Orbits MRI analysis at the first episode of ON has the potential to assess the visual function and VO in ON patients, and predict MS development.


Assuntos
Doenças Desmielinizantes/diagnóstico , Imageamento por Ressonância Magnética/métodos , Neurite Óptica/diagnóstico por imagem , Doença Aguda , Adulto , Feminino , Humanos , Imageamento Tridimensional , Masculino , Esclerose Múltipla/diagnóstico , Nervo Óptico/diagnóstico por imagem , Nervo Óptico/patologia , Neurite Óptica/patologia , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Acuidade Visual
10.
BMJ Case Rep ; 14(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431444

RESUMO

A 71-year-old man, living with metastatic castrate-resistant prostate cancer to the lymph nodes, spine and skull, presented with acute on chronic left eye vision loss. Examination revealed no-light-perception vision, a relative afferent pupillary defect and optic disc cupping. MRI brain revealed optic canal narrowing from metastatic sphenoid bone expansion and extraosseous tumour compressing the intracanalicular optic nerve. The optic disc cupping and excavation without significant pallor of the remaining neuroretinal rim was likely secondary to chronic compression of the optic nerve. The patient was treated with radiation therapy, but did not regain vision and was referred to palliative care as his condition continued to worsen. As patients live longer with advanced cancer, there is a greater risk of metastasis to atypical areas of the body including the optic nerve. This case demonstrates the unique combination of optic disc cupping from optic canal metastasis due to prostate cancer.


Assuntos
Cegueira/etiologia , Síndromes de Compressão Nervosa/etiologia , Nervo Óptico/patologia , Neoplasias Orbitárias/diagnóstico , Neoplasias da Próstata/patologia , Idoso , Cegueira/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Masculino , Síndromes de Compressão Nervosa/diagnóstico , Nervo Óptico/diagnóstico por imagem , Neoplasias Orbitárias/complicações , Neoplasias Orbitárias/radioterapia , Neoplasias Orbitárias/secundário , Neoplasias da Próstata/terapia , Radiocirurgia , Acuidade Visual
11.
J Neurovirol ; 27(1): 171-177, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33460014

RESUMO

The complete features of the neurological complications of coronavirus disease 2019 (COVID-19) still need to be elucidated, including associated cranial nerve involvement. In the present study we describe cranial nerve lesions seen in magnetic resonance imaging (MRI) of six cases of confirmed COVID-19, involving the olfactory bulb, optic nerve, abducens nerve, and facial nerve. Cranial nerve involvement was associated with COVID-19, but whether by direct viral invasion or autoimmunity needs to be clarified. The development of neurological symptoms after initial respiratory symptoms and the absence of the virus in the cerebrospinal fluid (CSF) suggest the possibility of autoimmunity.


Assuntos
Nervo Abducente/diagnóstico por imagem , Doenças dos Nervos Cranianos/diagnóstico por imagem , Nervo Facial/diagnóstico por imagem , Bulbo Olfatório/diagnóstico por imagem , Nervo Óptico/diagnóstico por imagem , Nervo Abducente/imunologia , Nervo Abducente/patologia , Nervo Abducente/virologia , Adulto , Idoso , Autoimunidade , /patologia , Doenças dos Nervos Cranianos/imunologia , Doenças dos Nervos Cranianos/patologia , Doenças dos Nervos Cranianos/virologia , Nervo Facial/imunologia , Nervo Facial/patologia , Nervo Facial/virologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Bulbo Olfatório/imunologia , Bulbo Olfatório/patologia , Bulbo Olfatório/virologia , Nervo Óptico/imunologia , Nervo Óptico/patologia , Nervo Óptico/virologia , /patogenicidade
13.
BMJ Case Rep ; 13(12)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33334745

RESUMO

Optic pathway cavernous malformations represent less than 1% of all central nervous system cavernomas. They can lead to visual loss with indeterminate speed, and therefore, the timing of intervention is controversial. We present a patient with an optic nerve cavernoma, which was discovered incidentally 3 years before the onset of visual symptoms. The evolution of her symptoms, visual function and radiographic findings are reported in detail. The cavernoma was eventually removed via a transciliary orbitocranial keyhole approach with the goal to protect the optic chiasm from progressive involvement. The function in the affected optic nerve was not salvageable. This is the second reported case of a cavernoma selectively involving the intracranial portion of the optic nerve. The debate on the timing of intervention is highlighted with reference to the natural history of these rare lesions.


Assuntos
Cegueira/etiologia , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias do Nervo Óptico/cirurgia , Adulto , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Humanos , Achados Incidentais , Imageamento por Ressonância Magnética , Nervo Óptico/patologia , Nervo Óptico/cirurgia , Neoplasias do Nervo Óptico/complicações , Neoplasias do Nervo Óptico/diagnóstico , Neoplasias do Nervo Óptico/patologia , Fatores de Tempo , Tempo para o Tratamento/normas , Conduta Expectante/normas
14.
Nat Commun ; 11(1): 5594, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154371

RESUMO

The underlying pathological mechanisms of glaucomatous trabecular meshwork (TM) damage and elevation of intraocular pressure (IOP) are poorly understood. Here, we report that the chronic endoplasmic reticulum (ER) stress-induced ATF4-CHOP-GADD34 pathway is activated in TM of human and mouse glaucoma. Expression of ATF4 in TM promotes aberrant protein synthesis and ER client protein load, leading to TM dysfunction and cell death. These events lead to IOP elevation and glaucomatous neurodegeneration. ATF4 interacts with CHOP and this interaction is essential for IOP elevation. Notably, genetic depletion or pharmacological inhibition of ATF4-CHOP-GADD34 pathway prevents TM cell death and rescues mouse models of glaucoma by reducing protein synthesis and ER client protein load in TM cells. Importantly, glaucomatous TM cells exhibit significantly increased protein synthesis along with induction of ATF4-CHOP-GADD34 pathway. These studies indicate a pathological role of ATF4-CHOP-GADD34 pathway in glaucoma and provide a possible treatment for glaucoma by targeting this pathway.


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Estresse do Retículo Endoplasmático , Glaucoma de Ângulo Aberto/metabolismo , Biossíntese de Proteínas , Fator 4 Ativador da Transcrição/antagonistas & inibidores , Fator 4 Ativador da Transcrição/genética , Animais , Humor Aquoso/metabolismo , Morte Celular , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/patologia , Humanos , Camundongos , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/metabolismo , Hipertensão Ocular/patologia , Nervo Óptico/metabolismo , Nervo Óptico/patologia , Biossíntese de Proteínas/efeitos dos fármacos , Proteína Fosfatase 1/genética , Proteína Fosfatase 1/metabolismo , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia , Transdução de Sinais , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/metabolismo , Malha Trabecular/patologia , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo
15.
PLoS One ; 15(10): e0240109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33007029

RESUMO

PURPOSE: To compare the properties of the lamina cribrosa (LC) and the peripapillary vessel density between branch retinal vein occlusion (BRVO) and normal-tension glaucoma (NTG), using swept-source optical coherence tomography and optical coherence tomography angiography. METHODS: This retrospective study included 21 eyes of 21 patients with BRVO and 43 eyes of 43 patients with NTG who were treated from June 2016 to September 2017. The anterior LC depth (ALCD) and LC thickness (LCT) at the mid-superior, central, and mid-inferior levels; the mean difference in ALCD; and the peripapillary vessel density in the superficial and deep capillary plexuses and the choriocapillaris were compared between groups. RESULTS: ALCD at the mid-superior, central, and mid-inferior levels was significantly greater in the NTG group (P < 0.05), while LCT was comparable between the groups. The mean difference in ALCD was significantly greater in the BRVO group (P = 0.03). The peripapillary vessel density in the superotemporal segment of the superficial capillary plexus was significantly lower in the BRVO group, while the density in all segments of the choriocapillaris was significantly lower in the NTG group (P < 0.05 for all). CONCLUSIONS: Our findings demonstrate that BRVO and NTG have different LC structures and peripapillary vessel densities.


Assuntos
Glaucoma de Baixa Tensão/patologia , Oclusão da Veia Retiniana/patologia , Vasos Retinianos/patologia , Idoso , Feminino , Fundo de Olho , Humanos , Glaucoma de Baixa Tensão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Nervo Óptico/diagnóstico por imagem , Nervo Óptico/patologia , Reprodutibilidade dos Testes , Oclusão da Veia Retiniana/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica
16.
BMC Neurol ; 20(1): 354, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962645

RESUMO

BACKGROUND: In acute large anterior circulation infarct patients with large core volume, we evaluated the role of optic nerve sheath diameter (ONSD) change rates in prediction of malignant progression. METHODS: We performed a retrospective observational study including patients with anterior circulation acute ischemic stroke with large ischemic cores from January 2010 to October 2017. Primary outcome was defined as undergoing decompressive surgery or death due to severe cerebral edema, and termed malignant progression. Patients were divided into malignant progressors and nonprogressors. Malignant progression was divided into early progression that occurred before D1 CT, and late progression that occurred afterwards. Retrospective analysis of changes in mean ONSD/eyeball transverse diameter (ETD) ratio, and midline shifting (MLS) were evaluated on serial computed tomography (CT). Through analysis of CT at baseline, postprocedure, and at D1, the predictive ability of time based change in ONSD/ETD ratio in predicting malignant progression was evaluated. RESULTS: A total of 58 patients were included. Nineteen (32.8%) were classified as malignant; 12 early, and 7 late progressions. In analysis of CTpostprocedure, A 1 mm/hr. rate of change in MLS during the CTbaseline-CTpostprocedure time phase lead to a 6.7 fold increased odds of early malignant progression (p < 0.05). For ONSD/ETD, 1%/hr. change lead to a 1.6 fold increased odds, but this association was trending (p = 0.249). In the CTD1, 1%/day change of ONSD/ETD in the CTbaseline-CTD1 time phase lead to a 1.4 fold increased odds of late malignant progression (p = 0.021) while 1 mm/day rate of change in MLS lead to a 1.5 fold increased odds (p = 0.014). CONCLUSIONS: The rate of ONSD/ETD changes compared to baseline at D1 CT can be a predictor of late malignant progression along with MLS. ONSD/ETD change rates evaluated at postprocedure did not predict early malignant progression.


Assuntos
Edema Encefálico/etiologia , Nervo Óptico/patologia , Acidente Vascular Cerebral/patologia , Edema Encefálico/patologia , Edema Encefálico/cirurgia , Craniotomia , Descompressão Cirúrgica , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Óptico/diagnóstico por imagem , Seleção de Pacientes , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/cirurgia , Tomografia Computadorizada por Raios X/métodos
17.
Ocul Immunol Inflamm ; 28(6): 922-925, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32870739

RESUMO

OBJECTIVE: To describe the ocular manifestations in a case of novel coronavirus disease 2019 (COVID-19). MATERIAL AND METHODS: A case of unilateral panuveitis and optic neuritis as initial presentation of COVID-19. RESULTS: As it is published, angiotensin-converting-enzyme-2 receptors can be found in many organs, such as the eyes, nerves, and vessels, so extrapulmonary involvement would be expected. According to current evidence and clinical characteristics of the patient, uveitis and optic neuritis could be produced by the virus. CONCLUSIONS: It is fundamental to consider panuveitis and optic neuritis as an unusual presentation of ocular involvement in COVID-19 so proper care can be given to the patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções Oculares Virais/etiologia , Neurite Óptica/etiologia , Pan-Uveíte/etiologia , Pneumonia Viral/complicações , Infecções por Coronavirus/epidemiologia , Infecções Oculares Virais/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Nervo Óptico/patologia , Neurite Óptica/diagnóstico , Pandemias , Pan-Uveíte/diagnóstico , Pneumonia Viral/epidemiologia , Tomografia de Coerência Óptica/métodos
18.
PLoS One ; 15(8): e0238104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822415

RESUMO

PURPOSE: To delineate responses of optic nerve head astrocytes to sustained intraocular pressure (IOP) elevation in mice. METHODS: We elevated IOP for 1 day to 6 weeks by intracameral microbead injection in 4 strains of mice. Astrocyte alterations were studied by transmission electron microscopy (TEM) including immunogold molecular localization, and by laser scanning microscopy (LSM) with immunofluorescence for integrin ß1, α-dystroglycan, and glial fibrillary acidic protein (GFAP). Astrocyte proliferation and apoptosis were quantified by Ki67 and TUNEL labeling, respectively. RESULTS: Astrocytes in normal optic nerve head expressed integrin ß1 and α-dystroglycan by LSM and TEM immunogold labeling at electron dense junctional complexes that were found only on cell membrane zones bordering their basement membranes (BM) at the peripapillary sclera (PPS) and optic nerve head capillaries. At 1-3 days after IOP elevation, abnormal extracellular spaces appeared between astrocytes near PPS, and axonal vesical and mitochondrial accumulation indicated axonal transport blockade. By 1 week, abnormal spaces increased, new collagen formation occurred, and astrocytes separated from their BM, leaving cell membrane fragments. Electron dense junctional complexes separated or were absent at the BM. Astrocyte proliferation was modest during the first week, while only occasional apoptotic astrocytes were observed by TEM and TUNEL. CONCLUSIONS: Astrocytes normally exhibit junctions with their BM which are disrupted by extended IOP elevation. Responses include reorientation of cell processes, new collagen formation, and cell proliferation.


Assuntos
Astrócitos/fisiologia , Glaucoma/patologia , Nervo Óptico/fisiologia , Animais , Apoptose , Astrócitos/citologia , Astrócitos/patologia , Proliferação de Células , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Pressão Intraocular , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Nervo Óptico/citologia , Nervo Óptico/patologia
19.
PLoS One ; 15(7): e0236450, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706792

RESUMO

Retinal ganglion cell (RGC) loss and optic neuropathy, both hallmarks of glaucoma, have been shown to involve N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity. This study investigated the neuroprotective effects of Philanthotoxin (PhTX)-343 in NMDA-induced retinal injury to alleviate ensuing visual impairments. Sprague-Dawley rats were divided into three; Group I was intravitreally injected with phosphate buffer saline as the control, Group II was injected with NMDA (160 nM) to induce retinal excitotoxic injury, while Group III was injected with PhTX-343 (160 nM) 24 h prior to excitotoxicity induction with NMDA. Rats were subjected to visual behaviour tests seven days post-treatment and subsequently euthanized. Rat retinas and optic nerves were subjected to H&E and toluidine blue staining, respectively. Histological assessments showed that NMDA exposure resulted in significant loss of retinal cell nuclei and thinning of ganglion cell layer (GCL). PhTX-343 pre-treatment prevented NMDA-induced changes where the RGC layer morphology is similar to the control. The numbers of nuclei in the NMDA group were markedly lower compared to the control (p<0.05). PhTX-343 group had significantly higher numbers of nuclei within 100 µm length and 100 µm2 area of GCL (2.9- and 1.7-fold, respectively) compared to NMDA group (p<0.05). PhTX-343 group also displayed lesser optic nerve fibres degeneration compared to NMDA group which showed vacuolation in all sections. In the visual behaviour test, the NMDA group recorded higher total distance travelled, and lower total immobile time and episodes compared to the control and PhTX-343 groups (p<0.05). Object recognition tests showed that the rats in PhTX-343 group could recognize objects better, whereas the same objects were identified as novel by NMDA rats despite multiple exposures (p<0.05). Visual performances in the PhTX-343 group were all comparable with the control (p>0.05). These findings suggested that PhTX-343 inhibit retinal cell loss, optic nerve damage, and visual impairments in NMDA-induced rats.


Assuntos
Fármacos Neuroprotetores , Traumatismos do Nervo Óptico/tratamento farmacológico , Nervo Óptico/efeitos dos fármacos , Fenóis , Poliaminas , Células Ganglionares da Retina/efeitos dos fármacos , Animais , Masculino , N-Metilaspartato/toxicidade , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Nervo Óptico/patologia , Traumatismos do Nervo Óptico/induzido quimicamente , Fenóis/farmacologia , Fenóis/uso terapêutico , Poliaminas/farmacologia , Poliaminas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Células Ganglionares da Retina/patologia , Visão Ocular/efeitos dos fármacos
20.
Medicine (Baltimore) ; 99(29): e20670, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702816

RESUMO

RATIONAL: Cavernous hemangiomas are one of the most common benign primary orbital lesions. These tumors are insidious in onset, slowly progressive and present more often in middle aged women. Multiple orbital cavernous hemangiomas are extremely rare, and only a few cases have been reported in the published literature. PATIENT CONCERNS: Here, we report the diagnosis and treatment of multiple cavernous hemangiomas in the right orbit of a female patient with impaired visual acuity and proptosis of the eye for more than 10 years. DIAGNOSIS: Magnetic resonance imaging of the orbit showed a giant and irregular soft mass filling the intraconal and extraconal space of the right orbit, compressing the right optic nerve. After tumor resection, histopathological examination confirmed the diagnosis of cavernous hemangioma. INTERVENTIONS: A lateral orbitotomy was performed and a total of 13 tumors were excised, with the largest tumor measuring approximately 2.5 × 3.0 cm. OUTCOMES: The visual acuity of the patient was preserved, with only a slightly dilated pupil of the right eye. The follow-up period was 6 months with no signs of recurrence. LESSONS: Multiple cavernous hemangiomas in the orbit is rare and should be excised surgically as soon as possible.


Assuntos
Hemangioma Cavernoso/cirurgia , Síndromes de Compressão Nervosa/etiologia , Nervo Óptico/patologia , Neoplasias Orbitárias/patologia , Adulto , Assistência ao Convalescente , Criança , Exoftalmia/etiologia , Feminino , Hemangioma Cavernoso/complicações , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Orbitárias/diagnóstico por imagem , Resultado do Tratamento , Transtornos da Visão/etiologia
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