Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.971
Filtrar
1.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-33462012

RESUMEN

Morning glory disc anomaly (MGDA) is most commonly found in white females in childhood with reduced vision. One in two cases have been reported to develop maculopathy or posterior pole retinal detachment as they grow older. The pathophysiology of MGDA-associated maculopathy is not well understood.We describe a 31-year-old black woman, who presented with gradual reduction of vision in the right eye due to MGDA-associated maculopathy. We identified morphological characteristics of the optic disc and macula with multicolour and optical coherence tomography imaging.We speculate that the centripetal inner retina traction and cerebrospinal fluid pressure fluctuation play an important role in inner retinal fluid accumulation in the pathology of retinoschisis in MGDA. Further studies will shed some light of a potential cause-and-effect relationship between MGDA and retinoschisis.


Asunto(s)
Disco Óptico/anomalías , Disco Óptico/diagnóstico por imagen , Enfermedades de la Retina/congénito , Enfermedades de la Retina/diagnóstico por imagen , Tomografía de Coherencia Óptica , Adulto , Femenino , Humanos , Enfermedades de la Retina/patología
2.
Arch. Soc. Esp. Oftalmol ; 95(12): 611-614, dic. 2020. ilus
Artículo en Español | IBECS | ID: ibc-197761

RESUMEN

CASO CLÍNICO: Presentamos tres casos de pacientes con hiperquilomicronemia familiar y lipemia retinalis, y analizamos de forma comparada las características fundoscópicas de cada uno de ellos. DISCUSIÓN: El aspecto característico del fondo retiniano en color salmón-pálido corresponde con grados severos de lipemia retinalis. Los hallazgos relativos a la tonalidad del árbol vascular en segmentos distales constituyen probablemente el dato exploratorio que mejor orienta el diagnóstico oftalmológico en niveles inferiores de hipertrigliceridemia


CASES REPORT: Three cases are presented of patients with familial hyperchylomicronaemia and lipaemia retinalis, in whom an analysis is made of the fundoscopic characteristics of each of them. DISCUSSION: The typical appearance of the retinal fundus is pale salmon coloured and corresponds to levels of severe lipaemia retinalis. As regards the findings, the vascular tree tonality is probably the best exploratory evidence to help in the ophthalmological diagnosis


Asunto(s)
Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Hiperlipoproteinemia Tipo I/diagnóstico por imagen , Oftalmoscopía/métodos , Hiperlipidemias/diagnóstico por imagen , Enfermedades de la Retina/diagnóstico por imagen , Hiperlipoproteinemia Tipo I/patología , Hiperlipidemias/patología , Enfermedades de la Retina/patología , Fondo de Ojo
3.
Am J Trop Med Hyg ; 103(5): 2026-2028, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32901600

RESUMEN

Ocular complications are rare in patients with dengue fever, but may cause permanent loss of vision. We present the case of a 29-year-old German woman who developed severe acute vision loss because of dengue-associated maculopathy after traveling to Vietnam and Cambodia. Initially, the optical coherence tomography showed detachment of the retinal pigment epithelium, a central shift in the retinal pigmentation and intraretinal cysts. The patient was hospitalized and treated with a short course of intravenous prednisolone. Vision improved, and the patient showed full recovery at 9 months after the onset. This case highlights the importance of awareness and adequate management for ocular involvement in patients with dengue fever, including travelers.


Asunto(s)
Dengue/diagnóstico por imagen , Enfermedades de la Retina/diagnóstico por imagen , Adulto , Cambodia , Dengue/complicaciones , Dengue/parasitología , Dengue/patología , Femenino , Alemania , Humanos , Degeneración Macular , Retina/diagnóstico por imagen , Retina/parasitología , Retina/patología , Enfermedades de la Retina/complicaciones , Enfermedades de la Retina/parasitología , Enfermedades de la Retina/patología , Tomografía de Coherencia Óptica , Viaje , Vietnam
4.
Neurology ; 95(14): e1918-e1931, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-32887784

RESUMEN

OBJECTIVE: To characterize lesion evolution and neurodegeneration in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) using multimodal MRI. METHODS: We prospectively performed MRI and cognitive testing in RVCL-S and healthy control cohorts. Gray and white matter volume and disruption of white matter microstructure were quantified. Asymmetric spin echo acquisition permitted voxel-wise oxygen extraction fraction (OEF) calculation as an in vivo marker of microvascular ischemia. The RVCL-S cohort was included in a longitudinal analysis of lesion subtypes in which hyperintense lesions on fluid-attenuated inversion recovery (FLAIR), T1-postgadolinium, and diffusion-weighted imaging were delineated and quantified volumetrically. RESULTS: Twenty individuals with RVCL-S and 26 controls were enrolled. White matter volume and microstructure declined faster in those with RVCL-S compared to controls. White matter atrophy in RVCL-S was highly linear (ρ = -0.908, p < 0.0001). Normalized OEF was elevated in RVCL-S and increased with disease duration. Multiple cognitive domains, specifically those measuring working memory and processing speed, were impaired in RVCL-S. Lesion volumes, regardless of subtype, progressed/regressed with high variability as a function of age, while FLAIR lesion burden increased near time to death (p < 0.001). CONCLUSION: RVCL-S is a monogenic microvasculopathy affecting predominantly the white matter with regard to atrophy and cognitive impairment. White matter volumes in RVCL-S declined linearly, providing a potential metric against which to test the efficacy of future therapies. Progressive elevation of white matter OEF suggests that microvascular ischemia may underlie neurodegeneration in RVCL-S.


Asunto(s)
Disfunción Cognitiva/patología , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/patología , Degeneración Nerviosa/patología , Enfermedades de la Retina/patología , Enfermedades Vasculares/patología , Sustancia Blanca/patología , Adulto , Disfunción Cognitiva/diagnóstico por imagen , Femenino , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Degeneración Nerviosa/diagnóstico por imagen , Neuroimagen/métodos , Enfermedades de la Retina/diagnóstico por imagen , Enfermedades Vasculares/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen
6.
Med Sci (Paris) ; 36(6-7): 626-632, 2020.
Artículo en Francés | MEDLINE | ID: mdl-32614314

RESUMEN

Generation of retinal organoids from pluripotent stem cells represents an important advance in the study of retinal development and offer new perspectives for the study of retinal diseases missing suitable animal models. Understanding the key stages of retinal development in vertebrates enabled to design protocols to generate self-organized three-dimensional structures derived from pluripotent stem cells and containing all retinal cell types. In addition to their application in basic research, such as the characterization of molecular and cellular mechanisms in retinal pathophysiology, these miniature organs also open up encouraging prospects in the field of cell therapy or the screening of therapeutic molecules, although some obstacles remain to be overcome.


Asunto(s)
Organoides/citología , Retina/citología , Enfermedades de la Retina/etiología , Enfermedades de la Retina/patología , Enfermedades de la Retina/terapia , Animales , Células Cultivadas , Humanos , Modelos Biológicos , Organoides/fisiología , Retina/patología , Retina/fisiología , Terapias en Investigación/métodos , Terapias en Investigación/tendencias , Técnicas de Cultivo de Tejidos/métodos , Técnicas de Cultivo de Tejidos/tendencias
7.
Proc Natl Acad Sci U S A ; 117(31): 18780-18787, 2020 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-32699144

RESUMEN

Macular telangiectasia type 2 (MacTel), a late-onset macular degeneration, has been linked to a loss in the retina of Müller glial cells and the amino acid serine, synthesized by the Müller cells. The disease is confined mainly to a central retinal region called the MacTel zone. We have used electron microscopic connectomics techniques, optimized for disease analysis, to study the retina from a 48-y-old woman suffering from MacTel. The major observations made were specific changes in mitochondrial structure within and outside the MacTel zone that were present in all retinal cell types. We also identified an abrupt boundary of the MacTel zone that coincides with the loss of Müller cells and macular pigment. Since Müller cells synthesize retinal serine, we propose that a deficiency of serine, required for mitochondrial maintenance, causes mitochondrial changes that underlie MacTel development.


Asunto(s)
Conectoma/métodos , Retina , Enfermedades de la Retina , Femenino , Humanos , Degeneración Macular/diagnóstico por imagen , Degeneración Macular/patología , Microscopía Electrónica , Persona de Mediana Edad , Retina/citología , Retina/diagnóstico por imagen , Retina/patología , Enfermedades de la Retina/diagnóstico por imagen , Enfermedades de la Retina/patología
8.
Int J Mol Sci ; 21(14)2020 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-32674481

RESUMEN

Effective treatment of retinal diseases with adeno-associated virus (AAV)-mediated gene therapy is highly dependent on the proportion of successfully transduced cells. However, due to inflammatory reactions at high vector doses, adjunctive treatment may be necessary to enhance the therapeutic outcome. Hydroxychloroquine and chloroquine are anti-malarial drugs that have been successfully used in the treatment of autoimmune diseases. Evidence suggests that at high concentrations, hydroxychloroquine and chloroquine can impact viral infection and replication by increasing endosomal and lysosomal pH. This effect has led to investigations into the potential benefits of these drugs in the treatment of viral infections, including human immunodeficiency virus and severe acute respiratory syndrome coronavirus-2. However, at lower concentrations, hydroxychloroquine and chloroquine appear to exert immunomodulatory effects by inhibiting nucleic acid sensors, including toll-like receptor 9 and cyclic GMP-AMP synthase. This dose-dependent effect on their mechanism of action supports observations of increased viral infections associated with lower drug doses. In this review, we explore the immunomodulatory activity of hydroxychloroquine and chloroquine, their impact on viral infections, and their potential to improve the efficacy and safety of retinal gene therapy by reducing AAV-induced immune responses. The safety and practicalities of delivering hydroxychloroquine into the retina will also be discussed.


Asunto(s)
Cloroquina/uso terapéutico , Terapia Genética , Hidroxicloroquina/uso terapéutico , Enfermedades de la Retina/terapia , Virosis/tratamiento farmacológico , Animales , Betacoronavirus/efectos de los fármacos , Cloroquina/farmacología , Dependovirus/genética , Humanos , Hidroxicloroquina/farmacología , Inmunomodulación/efectos de los fármacos , Enfermedades de la Retina/patología
9.
J Fr Ophtalmol ; 43(8): 727-730, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32620415

RESUMEN

We report a case of a patient treated with tamoxifen 20mg daily as hormone therapy for breast cancer. On regular ophthalmological follow-up, tamoxifen maculopathy was detected on SD-OCT (Spectral Domain Optic Coherence Tomography, Carl Zeiss Meditec®), so the medication was discontinued. Despite discontinuation of the medication, the maculopathy progressed over time. We have been following our patient for seven years. Tamoxifen may produce a toxic maculopathy which may progress despite discontinuation of the medication. We consider our case interesting, given the lengthy follow-up of the patient with sequential SD-OCT images. To the best of our knowledge, our case represents the longest follow-up period for a patient with tamoxifen maculopathy. Moreover, we would like to stress the importance of screening in asymptomatic patients on this medication, in order to detect early pathological signs.


Asunto(s)
Monitoreo Fisiológico , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/diagnóstico , Tamoxifeno/efectos adversos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Humanos , Mácula Lútea/efectos de los fármacos , Mácula Lútea/patología , Degeneración Macular/inducido químicamente , Degeneración Macular/diagnóstico , Degeneración Macular/patología , Monitoreo Fisiológico/métodos , Enfermedades de la Retina/patología , Tamoxifeno/administración & dosificación , Tomografía de Coherencia Óptica
10.
PLoS One ; 15(6): e0234151, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32520956

RESUMEN

OBJECTIVES: To examine interocular asymmetry of foveal avascular zone (FAZ) and parafoveal capillary density metrics in sickle cell retinopathy (SCR) using optical coherence tomography angiography (OCT-A). METHODS: This cross-sectional, retrospective study evaluated SCR patients and unaffected controls who underwent 3x3mm macular OCT-A imaging using a spectral domain-OCT system. FAZ (area, perimeter, and acircularity index) and parafoveal capillary density metrics were computed for both eyes of each participant. In unaffected controls, interocular difference in FAZ and parafoveal capillary density metrics were evaluated using Bland-Altman plots. SCR patients with interocular difference outside the upper 97.5% and lower 2.5% limits of agreement from controls were defined as having interocular asymmetry. Area under receiver operating characteristic curve (AROC) was also performed to determine the ability of the absolute interocular difference to differentiate between subjects with SCR-including non-proliferative SCR (NP-SCR) and proliferative SCR (P-SCR)-and unaffected controls. RESULTS: Thirty-one patients with SCR (21 NP-SCR and 10 P-SCR) and 14 race-matched and age-matched controls were included for analysis. Interocular asymmetry was seen for all FAZ and parafoveal capillary density metrics in NP-SCR and P-SCR subjects. SCR subjects showed greater disease severity in the left-eye for FAZ and parafoveal capillary density metrics. CONCLUSIONS: NP-SCR and P-SCR patients demonstrated quantifiable interocular asymmetry in FAZ and parafoveal capillary density metrics compared to unaffected subjects, with left-eye predominance in disease severity.


Asunto(s)
Anemia de Células Falciformes/patología , Capilares/fisiología , Fóvea Central/fisiología , Enfermedades de la Retina/patología , Adulto , Anemia de Células Falciformes/complicaciones , Área Bajo la Curva , Estudios de Casos y Controles , Estudios Transversales , Ojo/diagnóstico por imagen , Femenino , Fóvea Central/irrigación sanguínea , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Enfermedades de la Retina/etiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía de Coherencia Óptica , Adulto Joven
12.
Am J Pathol ; 190(8): 1723-1734, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32389572

RESUMEN

Retinal ischemic events, which result from occlusion of the ocular vasculature share similar causes as those for central nervous system stroke and are among the most common cause of acute and irreversible vision loss in elderly patients. Currently, there is no established treatment, and the condition often leaves patients with seriously impaired vision or blindness. The immune system, particularly T-cell-mediated responses, is thought to be intricately involved, but the exact roles remain elusive. We found that acute ischemia-reperfusion injury to the retina induced a prolonged phase of retinal ganglion cell loss that continued to progress during 8 weeks after the procedure. This phase was accompanied by microglial activation and CD4+ T-cell infiltration into the retina. Adoptive transfer of CD4+ T cells isolated from diseased mice exacerbated retinal ganglion cell loss in mice with retinal reperfusion damage. On the other hand, T-cell deficiency or administration of T-cell or interferon-γ-neutralizing antibody attenuated retinal ganglion cell degeneration and retinal function loss after injury. These findings demonstrate a crucial role for T-cell-mediated responses in the pathogenesis of neural ischemia. These findings point to novel therapeutic targets of limiting or preventing neuron and function loss for currently untreatable conditions of optic neuropathy and/or central nervous system ischemic stroke.


Asunto(s)
Linfocitos T CD4-Positivos/patología , Isquemia/patología , Retina/patología , Degeneración Retiniana/patología , Enfermedades de la Retina/patología , Vasos Retinianos/patología , Traslado Adoptivo , Animales , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Ratones , Células Ganglionares de la Retina/patología
15.
Medicine (Baltimore) ; 99(15): e19794, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32282743

RESUMEN

RATIONALE: Multiple evanescent white dot syndrome (MEWDS) is a self-limited multifocal chorioretinopathy that typically affects otherwise healthy young females in the second to fourth decades of life. Current understanding of the pathophysiology of MEWDS is still limited. One of the possible underlying causes is an infectious etiology. PATIENT CONCERNS: A 24-year-old female with recurrent episodes of typical MEWDS ocular manifestation was observed over 2 years. Viral-specific antibody serologic tests showed evidence of exposure to the Herpesviridae family during the acute stage of MEWDS in the first and recurrent episodes. DIAGNOSES: MEWDS was diagnosed by the clinical findings and ancillary testing results of fundus photography, optical coherence tomography, fluorescein angiography, indocyanine green angiography and electroretinogram. The laboratory serology data was positive for varicella-zoster virus (VZV) immunoglobulin M (IgM) in the first episode and exhibited high Epstein-Barr virus (EBV) elevated immunoglobulin G (IgG) titer in the recurrent episode. INTERVENTIONS: Due to the self-limited nature of MEWDS, we observed the clinical course without intervention. OUTCOMES: During acute onset of MEWDS, serologic data for VZV IgM antibody was positive in the first episode. Two years later, the patient had recurrent episodes of MEWDS in the contralateral eye. Serologic study showed highly elevated IgG titer (1:160) of Epstein-Barr virus capsid antigen (EB-VCA) in the acute stage. The follow-up paired serum virus serology test showed that the prior EB-VCA IgG titer decreased fourfold to 1:40 in the recovery stage. LESSONS: Recurrence of MEWDS may be associated with acute systemic infection of the Herpesviridae family or virus-induced autoimmune inflammatory reaction.


Asunto(s)
Infecciones por Herpesviridae/complicaciones , Herpesviridae/inmunología , Enfermedades de la Retina/virología , Síndromes de Puntos Blancos/virología , Angiografía/métodos , Antígenos Virales/inmunología , Grupo de Ascendencia Continental Asiática/etnología , Proteínas de la Cápside/inmunología , Electrorretinografía/métodos , Femenino , Angiografía con Fluoresceína/métodos , Fondo de Ojo , Infecciones por Herpesviridae/virología , Herpesvirus Humano 3/inmunología , Herpesvirus Humano 4/inmunología , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Verde de Indocianina/administración & dosificación , Recurrencia , Enfermedades de la Retina/diagnóstico por imagen , Enfermedades de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Síndromes de Puntos Blancos/diagnóstico por imagen , Síndromes de Puntos Blancos/etiología , Adulto Joven
16.
Zhonghua Yan Ke Za Zhi ; 56(4): 258-265, 2020 Apr 11.
Artículo en Chino | MEDLINE | ID: mdl-32306617

RESUMEN

Objective: To investigate the characteristics of retinal nerve fiber layer (RNFL) thickness in AIDS patients with normal fundus, HIV-related microvascular retinopathy (MVR), and cytomegalovirus retinitis (CMVR). Methods: In this cross-sectional study, 111 patients were diagnosed with AIDS from 2012 to 2017 by infectious disease physicians in Beijing You'an Hospital. There were 105 males and 6 females, aged 20-65 years. According to the results of ophthalmic examination, the patients were divided into three groups: 31 patients in the active-stage CMVR group, 47 patients in the MVR group, and 33 patients with normal fundus in the control group. RNFL thickness was measured by optical coherence tomography in all patients. At the same time, visual acuity, intraocular pressure, and fundus were examined, and AIDS-related systemic examination (CD4(+) T lymphocyte count, HAART treatment status, and blood cytomegalovirus DNA level) was performed. The measurement data were compared by t-test, variance analysis or rank sum test. The counting data were compared by chi square test or Fisher exact probability method. Results: In the control group, the thickness of RNFL in the superior quadrant in the left and right eyes was 145 (79, 231) µm and 142 (46, 179) µm, respectively; the difference was statistically significant (Z=-2.481, P=0.013). The RNFL thickness of the diseased and healthy eyes in the MVR group was 116 (91, 138) µm and 122 (82, 192) µm, respectively, with no significant difference (Z=-0.861, P=0.389); the best corrected visual acuity was 0.0 (0.0, 0.2) and 0.0 (0.0, 0.2), respectively, with no significant difference (Z=-0.378, P=0.705). In the CMVR group, the best corrected visual acuity of the diseased and healthy eyes was (0.23±0.48) and (0.02±0.82), respectively, and the difference was statistically significant (t=-2.944, P=0.003); the RNFL thickness was 133 (61, 219) µm and 121 (69, 146), respectively, in the whole optic disc, with statistically significant difference (Z=-2.385, P=0.017), 104 (41, 374) µm and 82 (55, 121) µm, respectively, in the nasal quadrant, and 99 (14, 173) µm and 72 (36, 111) µm, respectively, in the temporal quadrant, with statistically significant difference (Z=-2.045, -2.543; P=0.041, 0.011). The RNFL thickness in the CMVR group, the MVR group, and the control group was 149 (61, 350) µm, 126 (71, 304) µm, and 113 (87, 149) µm, respectively, with statistically significant difference (H=20.908, P=0.000). Conclusions: The fundus of AIDS patients had different characteristics on optical coherence tomography. In active CMVR patients, the thickness of RNFL was generally thickened. In MVR patients, the average thickness of RNFL was thicker than that in the normal control group.(Chin J Ophthalmol, 2020, 56:258-265).


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Retinitis por Citomegalovirus/patología , Fibras Nerviosas/patología , Disco Óptico , Enfermedades de la Retina/patología , Adulto , Anciano , Estudios Transversales , Retinitis por Citomegalovirus/complicaciones , Femenino , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Retina/complicaciones , Tomografía de Coherencia Óptica , Adulto Joven
17.
Medicine (Baltimore) ; 99(16): e19875, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32312013

RESUMEN

INTRODUCTION: Systemic lupus erythematosus (SLE) is a multisystem, chronic, autoimmune disease which can affect any organ system including the eye. About one-third of the patients can be diagnosed with SLE-related eye involvement which is usually indicative of disease activity. Retinopathy is one of the most vision-threatening complications that can be associated with the disease. PATIENT CONCERNS: An 11-year-old girl was hospitalized with complains of repeated swelling and pain in her extremities for 1 month, chest pain for 24 days, rash for 5 days and proteinuria for 1 day. On the morning of her fourth day in hospital, she suddenly complained of sudden, painless vision loss in the left eye. The ophthalmologist found that she had obstruction of central retinal vein and artery with diffuse retinal hemorrhages and macular edema. DIAGNOSIS: The patient was diagnosed with systemic lupus erythematosus, lupus nephritis, and lupus retinopathy through her clinical manifestations and laboratory tests. INTERVENTIONS: After diagnosis, she received steroid therapy, retinal laser photocoagulation, and intravitreal injection of dexamethasone (OZURDEX, Allergan Pharmaceuticals, Dublin, Ireland) early in her course. OUTCOMES: At the latest follow-up, her vision improved partially. However, she still has the possibility of subsequent neovascular glaucoma and bleeding in the future. CONCLUSIONS: An early diagnosis and the prompt therapeutic measures are necessary to prevent sight-threatening consequences, especially in pediatric patients with SLE.


Asunto(s)
Lupus Eritematoso Sistémico/complicaciones , Enfermedades de la Retina/etiología , Enfermedades de la Retina/terapia , Trastornos de la Visión/etiología , Niño , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Femenino , Glaucoma Neovascular/epidemiología , Glaucoma Neovascular/etiología , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Hemorragia , Humanos , Inyecciones Intravítreas , Coagulación con Láser/métodos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/patología , Nefritis Lúpica/complicaciones , Nefritis Lúpica/diagnóstico , Edema Macular , Oclusión de la Arteria Retiniana/diagnóstico , Oclusión de la Arteria Retiniana/etiología , Enfermedades de la Retina/patología , Oclusión de la Vena Retiniana/diagnóstico , Oclusión de la Vena Retiniana/etiología , Resultado del Tratamiento
18.
Proc Natl Acad Sci U S A ; 117(16): 9001-9012, 2020 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-32265282

RESUMEN

The interplay of transcription factors and cis-regulatory elements (CREs) orchestrates the dynamic and diverse genetic programs that assemble the human central nervous system (CNS) during development and maintain its function throughout life. Genetic variation within CREs plays a central role in phenotypic variation in complex traits including the risk of developing disease. We took advantage of the retina, a well-characterized region of the CNS known to be affected by pathogenic variants in CREs, to establish a roadmap for characterizing regulatory variation in the human CNS. This comprehensive analysis of tissue-specific regulatory elements, transcription factor binding, and gene expression programs in three regions of the human visual system (retina, macula, and retinal pigment epithelium/choroid) reveals features of regulatory element evolution that shape tissue-specific gene expression programs and defines regulatory elements with the potential to contribute to Mendelian and complex disorders of human vision.


Asunto(s)
Evolución Molecular , Regulación del Desarrollo de la Expresión Génica , Secuencias Reguladoras de Ácidos Nucleicos/genética , Retina/patología , Enfermedades de la Retina/genética , Adulto , Animales , Análisis Mutacional de ADN , Epigenómica , Femenino , Variación Genética , Humanos , Masculino , Ratones , Persona de Mediana Edad , Mutación , RNA-Seq , Retina/crecimiento & desarrollo , Enfermedades de la Retina/patología , Especificidad de la Especie
19.
Exp Eye Res ; 193: 107997, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32165157

RESUMEN

We aimed to assess the neuroprotective effect of a pyruvate dehydrogenase kinase (PDK) inhibitor, Nov3r after ischemia/reperfusion (IR) injury in rats. IR injury was induced by applying 150 mmHg of intraocular pressure for 50 min. Nov3r was orally administered (100 mg/kg) 3 h before and 24 h after IR injury. TUNEL-positive cells increased and immunoreactive RBPMS-positive cells decreased in the rat retinas after IR injury. Administration of Nov3r significantly ameliorated the increase in TUNEL-positive cells and prevented the RBPMS-positive cell decrease. Similarly, the number of IR-induced Iba1-positive microglial cells was significantly reduced with Nov3r treatment. Among metabolic parameters, IR damage induced the elevation of lactate and pyruvate, and the reduction of ATP. Oral administration of Nov3r ameliorated these changes. Our data suggest that the Nov3r had a retinal neuroprotective effect in IR injury in rats. This finding suggests that the regulation of pyruvate dehydrogenase (PDH) activity has potential therapeutic value by enabling metabolic reprograming in diseases associated with ischemic retinal damage, such as diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, ischemic optic neuropathy and glaucoma.


Asunto(s)
Metabolismo Energético/fisiología , Daño por Reperfusión/prevención & control , Enfermedades de la Retina/prevención & control , Células Ganglionares de la Retina/patología , Animales , Muerte Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Masculino , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/patología , Células Ganglionares de la Retina/efectos de los fármacos
20.
Sci Rep ; 10(1): 4251, 2020 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-32144342

RESUMEN

In glaucoma, retinal ganglion cells are damaged, leading to the progressive constriction of the visual field. We have previously shown that the valosin-containing protein (VCP) modulators, Kyoto University Substance (KUS)121 and KUS187, prevent the death of retinal ganglion cells in animal models of glaucoma, including the one generated by N-methyl-D-aspartate (NMDA)-induced neurotoxicity. KUSs appeared to avert endoplasmic reticulum (ER) stress by maintaining ATP levels, resulting in the protection of ganglion cells from cell death. To further elucidate the protective mechanisms of KUSs, we examined gene expression profiles in affected ganglion cells. We first injected KUS-treated mice with NMDA and then isolated the affected retinal ganglion cells using fluorescence-activated cell sorting. Gene expression in the cells was quantified using a next-generation sequencer. Resultantly, we found that KUS121 upregulated several genes involved in energy metabolism. In addition, we observed the upregulation of Zfp667, which has been reported to suppress apoptosis-related genes and prevent cell death. These results further support the suitability of KUS121 as a therapeutic drug in protecting retinal ganglion cells in ophthalmic disorders, such as glaucoma.


Asunto(s)
Susceptibilidad a Enfermedades , Enfermedades de la Retina/etiología , Enfermedades de la Retina/metabolismo , Células Ganglionares de la Retina/metabolismo , Transcriptoma , Proteína que Contiene Valosina/genética , Proteína que Contiene Valosina/metabolismo , Enfermedad Aguda , Animales , Apoptosis , Biomarcadores , Biología Computacional/métodos , Modelos Animales de Enfermedad , Metabolismo Energético , Perfilación de la Expresión Génica , Ontología de Genes , Inmunofenotipificación , Redes y Vías Metabólicas , Ratones , N-Metilaspartato/efectos adversos , Enfermedades de la Retina/patología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...