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2.
Ophthalmol Retina ; 4(7): e5, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32646558
4.
Ophthalmol Retina ; 4(7): e6-e7, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32646560
6.
Medicine (Baltimore) ; 99(26): e21007, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590817

RESUMO

The aim of this study was to investigate the changes of retinal vessel density (VD) and choriocapillary blood flow area (CBFA) in macula after an acute intraocular pressure (IOP) elevation observed using optical coherence tomography angiography.This was a prospective comparative study of subjects with narrow anterior chamber angles who underwent laser peripheral iridotomies (LPIs). The IOP was measured before and 1 hour after the LPI. The retinal VDs and CBFAs of the macula were measured using optical coherence tomography angiography at the baseline and 1 hour after the LPI.A total of 88 eyes of 88 individuals were enrolled in our study, and 70 eyes of 70 individuals finally completed the study with a mean IOP rise of 10.2 ±â€Š7.5 mm Hg after the LPI. The VDs and areas of foveal avascular zone of all of the subjects did not differ significantly between the measurements obtained at the baseline and 1 hour after the LPI (P > .05). However, there were statistically significant differences in the CBFAs at the baseline and 1 hour after the LPI (P < .05). Based on the magnitude of the rise in the IOP, we divided the subjects into three groups: group A = IOP rise ≤ 10 mm Hg, group B = 10 mm Hg < IOP rise ≤20 mm Hg, and group C = IOP rise > 20 mmHg. The VDs of the macula measured at the baseline were significantly different from the measurements obtained 1 hour after the LPI in group C in either the superficial retinal layer or deep retinal layer (P < .05). Compared with baseline, the CBFAs measured at 1 hour after the LPI were decreased in group B and group C (P < .05).In these subjects with narrow antenior chamber, the blood flow in macula began to be affected with the acute IOP rise greater than 10 mm Hg. It was confirmed that the retina and choroid showed some different ability to regulate its blood flow in response to changes in IOP.


Assuntos
Corioide/irrigação sanguínea , Macula Lutea/irrigação sanguínea , Hipertensão Ocular/fisiopatologia , Retina/fisiopatologia , Idoso , Capilares , Corioide/fisiopatologia , Feminino , Humanos , Pressão Intraocular , Macula Lutea/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica/métodos
7.
J Environ Pathol Toxicol Oncol ; 39(1): 89-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479015

RESUMO

Oxidative stress and inflammation are regarded as prime reasons for the progression and development of diabetic retinopathy. Currently, nuclear factor erythroid-2-related factor 2 (Nrf2), thioredoxin interacting protein (TXNIP) and NLRP3 inflammasome pathways are under increasing focus in research on oxidative stress and inflammation-related diseases. On the other hand, tilianin (TN) has received much attention because of its various pharmacological properties. Based on results of these studies, this investigation was performed to inspect the therapeutic efficiency of TN on the retina in diabetic rats. Rats were arbitrarily assigned to three groups: control group, diabetic group, and diabetic plus TN (20 mg/ kg body weight for 42 days, orally) group. TN supplementation in diabetic rats, their food intake, fasting blood glucose status, glycosylated hemoglobin (HbA1c) levels were drastically reduced, and there was a marked augmentation in serum insulin status. TN treatment of diabetic rats increased mRNA expression of Nrf2 and its target gene, HO-1, and noticeably decreased the malondialdehyde status. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidases (GPX) were increased relative to diabetic rats. Furthermore, administering TN to the diabetic rats resulted in decreased expression of TXNIP, NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and IL-1ß proteins and decreased distribution of TXNIP, NLRP3, ASC, and caspase-1 proteins in retinas. In addition, TN treatment ameliorated morphological and morphometric changes in the retinas of diabetic rats. Together, all of these findings provide clear evidence that TN treatment of diabetic rats attenuated diabetic retinal changes through its hypoglycemic, antioxidant, and anti-inflammatory properties. The antioxidant and anti-inflammatory effects in diabetic retinas occur at least in part through the modulation of Nrf2/TXNIP/NLRP3 inflammasome pathways, which may have remedial benefits in the healing of diabetic retinopathy.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Flavonoides/farmacologia , Glicosídeos/farmacologia , Inflamassomos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Retina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ração Animal/análise , Animais , Dieta , Suplementos Nutricionais/análise , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Retina/patologia
8.
Nature ; 581(7807): 194-198, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32404998

RESUMO

Daily changes in light and food availability are major time cues that influence circadian timing1. However, little is known about the circuits that integrate these time cues to drive a coherent circadian output1-3. Here we investigate whether retinal inputs modulate entrainment to nonphotic cues such as time-restricted feeding. Photic information is relayed to the suprachiasmatic nucleus (SCN)-the central circadian pacemaker-and the intergeniculate leaflet (IGL) through intrinsically photosensitive retinal ganglion cells (ipRGCs)4. We show that adult mice that lack ipRGCs from the early postnatal stages have impaired entrainment to time-restricted feeding, whereas ablation of ipRGCs at later stages had no effect. Innervation of ipRGCs at early postnatal stages influences IGL neurons that express neuropeptide Y (NPY) (hereafter, IGLNPY neurons), guiding the assembly of a functional IGLNPY-SCN circuit. Moreover, silencing IGLNPY neurons in adult mice mimicked the deficits that were induced by ablation of ipRGCs in the early postnatal stages, and acute inhibition of IGLNPY terminals in the SCN decreased food-anticipatory activity. Thus, innervation of ipRGCs in the early postnatal period tunes the IGLNPY-SCN circuit to allow entrainment to time-restricted feeding.


Assuntos
Ritmo Circadiano/fisiologia , Comportamento Alimentar/fisiologia , Luz , Vias Neurais , Retina/fisiologia , Animais , Axônios/fisiologia , Axônios/efeitos da radiação , Ritmo Circadiano/efeitos da radiação , Sinais (Psicologia) , Ingestão de Alimentos/fisiologia , Ingestão de Alimentos/efeitos da radiação , Comportamento Alimentar/efeitos da radiação , Feminino , Corpos Geniculados/citologia , Corpos Geniculados/fisiologia , Corpos Geniculados/efeitos da radiação , Masculino , Camundongos , Vias Neurais/efeitos da radiação , Neuropeptídeo Y/metabolismo , Retina/citologia , Retina/efeitos da radiação , Células Ganglionares da Retina/fisiologia , Células Ganglionares da Retina/efeitos da radiação , Transdução de Sinais/efeitos da radiação , Núcleo Supraquiasmático/citologia , Núcleo Supraquiasmático/fisiologia , Núcleo Supraquiasmático/efeitos da radiação , Fatores de Tempo
9.
PLoS One ; 15(5): e0232785, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469871

RESUMO

BACKGROUND: Alzheimer's disease (AD) pathology precedes symptoms and its detection can identify at-risk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) Aß42 (A) and tau (T) ratio. METHODS: As part of an ongoing longitudinal study, we enrolled CH individuals, excluding those with cognitive impairment and significant ocular pathology. We classified the CH group into two sub-groups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27), using a logistic regression model from the CSF AT ratio that identified >85% of patients with a clinically probable AD diagnosis. Spectral-domain optical coherence tomography (OCT) was acquired for RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness. Group differences were tested using mixed model repeated measures and a classification model derived using multiple logistic regression. RESULTS: Mean age (± standard deviation) in the CH-PAT group (n = 27; 75.2 ± 8.4 years) was similar (p = 0.50) to the CH-NAT group (n = 16; 74.1 ± 7.9 years). Mean RNFL (standard error) was thinner in the CH-PAT group by 9.8 (2.7) µm; p < 0.001. RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity. CONCLUSIONS: Our retinal data predict which individuals have CSF biomarkers of AD pathology before cognitive deficits are detectable with 87% sensitivity. Such results from easy-to-acquire, objective and non-invasive measurements of the RNFL merit further study of OCT technology to monitor or screen for early AD pathology.


Assuntos
Doença de Alzheimer/genética , Peptídeos beta-Amiloides/genética , Disfunção Cognitiva/genética , Proteínas tau/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Amiloidose/líquido cefalorraquidiano , Amiloidose/diagnóstico por imagem , Amiloidose/genética , Amiloidose/patologia , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/metabolismo , Fibras Nervosas/patologia , Disco Óptico/diagnóstico por imagem , Disco Óptico/metabolismo , Disco Óptico/patologia , Retina/diagnóstico por imagem , Retina/metabolismo , Retina/patologia , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Proteínas tau/líquido cefalorraquidiano
10.
PLoS One ; 15(5): e0232779, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32365083

RESUMO

Apoptosis of neurovascular cells, including astroglial cells, contributes to the pathogenesis of diseases in which neurovascular disruption plays a central role. Bim is a pro-apoptotic protein that modulates not only apoptosis but also various cellular functions such as migration and extracellular matrix protein expression. Astroglial cells act as an intermediary between neural and vascular cells facilitating retinal vascular development and remodeling while maintaining normal vascular function and neuronal integrity. We previously showed that Bim deficient (Bim -/-) mice were protected from hyperoxia mediated vessel obliteration and ischemia-mediated retinal neovascularization. However, the underlying mechanisms and more specifically the role Bim expression in astroglial cells play remains elusive. Here, using retinal astroglial cells prepared from wild-type and Bim -/- mice, we determined the impact of Bim expression in retinal astroglial cell function. We showed that astroglial cells lacking Bim expression demonstrate increased VEGF expression and altered matricellular protein production including increased expression of thrombospondin-2 (TSP2), osteopontin and SPARC. Bim deficient astroglial cells also exhibited altered proliferation, migration, adhesion to various extracellular matrix proteins and increased expression of inflammatory mediators. Thus, our data emphasizes the importance of Bim expression in retinal astroglia cell autonomous regulatory mechanisms, which could influence neurovascular function.


Assuntos
Astrócitos/metabolismo , Proteína 11 Semelhante a Bcl-2/genética , Inflamação/genética , Retina/metabolismo , Animais , Apoptose/genética , Astrócitos/patologia , Movimento Celular/genética , Proliferação de Células/genética , Proteínas da Matriz Extracelular/genética , Regulação da Expressão Gênica/genética , Humanos , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Neovascularização Fisiológica/genética , Neurônios/metabolismo , Osteonectina/genética , Osteopontina/genética , Retina/patologia , Trombospondinas/genética , Fator A de Crescimento do Endotélio Vascular/genética
11.
PLoS One ; 15(5): e0232700, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392207

RESUMO

PURPOSE: To analyze the relationships between qualitative and quantitative parameters of spectral-domain optical coherence tomography (SD-OCT) and the central retinal sensitivity in patients with retinitis pigmentosa (RP). MATERIALS AND METHODS: Ninety-three eyes of 93 patients were finally enrolled, with a median age (quartile) of 58 (24.5) years. We assessed the patients using SD-OCT and the 10-2 program of a Humphry Field Analyzer (HFA). As a qualitative parameter, two graders independently classified the patients' SD-OCT images into five severity grades (grades 1-5) based on the severity of damage to the photoreceptor inner and outer segments (IS/OS) layer. As quantitative parameters, we measured the IS-ellipsoid zone (IS-EZ) width, IS/OS thickness, outer nuclear layer (ONL) thickness, central macular thickness (CMT, 1 and 3 mm) and macular cube (6 × 6 mm) volume and thickness. The central retinal sensitivity was defined by the best-corrected visual acuity (BCVA; logMAR), average sensitivities of the central 4 (foveal sensitivity [FS]) and 12 (macular sensitivity [MS]) points of the HFA 10-2 program and the mean deviation (MD) of the 10-2 program. Spearman's correlation was used to assess the association between both qualitative and quantitative parameters and variables of the central retinal sensitivity. In addition, we performed a multiple regression analysis using these parameters to identify the parameters most strongly influencing the central retinal sensitivity. RESULTS: The IS/OS severity grade was significantly correlated with the BCVA (ρ = 0.741, P < 0.001), FS (ρ = -0.844, P < 0.001), MS (ρ = -0.820, P < 0.001) and MD (ρ = -0.681, P < 0.001) and showed stronger correlations to them than any other quantitative parameters including the IS-EZ width, IS/OS thickness, ONL thickness, CMTs and macular cube volume/thickness. Furthermore, a step-wise multiple regression analysis indicated that the IS/OS severity grade was more strongly associated with the BCVA (ß = 0.659, P < 0.001), FS (ß = -0.820, P < 0.001), MS (ß = -0.820, P < 0.001) and MD (ß = -0.674, P < 0.001) than any other quantitative parameters. The intraclass correlation coefficient between two graders indicated substantial correlation (κ = 0.70). DISCUSSION: The qualitative grading of OCT based on the severity of the IS/OS layer was simple and strongly correlated with the central retinal sensitivity in patients with RP. It may be useful to assess the central visual function in patients with RP, although there is some variation in severity within the same severity grade.


Assuntos
Retina/diagnóstico por imagem , Retina/fisiopatologia , Retinite Pigmentosa/diagnóstico por imagem , Retinite Pigmentosa/fisiopatologia , Tomografia de Coerência Óptica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Retina/patologia , Adulto Jovem
13.
Proc Biol Sci ; 287(1927): 20200607, 2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32396797

RESUMO

The human visual field, on the temporal side, extends to at least 90° from the line of sight. Using a two-alternative forced-choice procedure in which observers are asked to report the direction of motion of a Gabor patch, and taking precautions to exclude unconscious eye movements in the direction of the stimulus, we show that the limiting eccentricity of image-forming vision can be established with precision. There are large, but reliable, individual differences in the limiting eccentricity. The limiting eccentricity exhibits a dependence on log contrast; but it is not reduced when the modulation visible to the rods is attenuated, a result compatible with the histological evidence that the outermost part of the retina exhibits a high density of cones. Our working hypothesis is that only one type of neural channel is present in the far periphery of the retina, a channel that responds to temporally modulated stimuli of low spatial frequency and that is directionally selective.


Assuntos
Campos Visuais , Sensibilidades de Contraste , Feminino , Humanos , Movimento (Física) , Retina , Células Fotorreceptoras Retinianas Cones , Acuidade Visual
14.
Nature ; 581(7808): 264-265, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32433616
15.
Am J Pathol ; 190(5): 1080-1094, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32354571

RESUMO

This study explored the anti-inflammatory effects of a glucagon-like peptide-1 receptor agonist (GLP-1RA), known as lixisenatide, on the eyes of early type 2 diabetic mice. Diabetic (db/db) mice were divided into three groups: GLP-1RA [lixisenatide (LIX)], insulin (INS) with controlled hyperglycemia based on the glucose concentration of lixisenatide, and diabetic control (D-CON). Nondiabetic control mice (db/dm) were also characterized for comparison. After 8 weeks of treatment, mRNA levels of inflammatory markers, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, immunohistochemical staining; Western blot of glial fibrillary acidic protein (GFAP) and thioredoxin-interacting protein; and retinal thickness were assessed in the central and peripheral neurosensory retina. LIX showed decreased immunohistochemical staining for both thioredoxin-interacting protein and GFAP in the central and peripheral neurosensory retina compared with D-CON and INS, and decreased expression of these proteins in the neurosensory retina and immunohistochemical staining in the optic nerve head for GFAP compared with D-CON. The inner nuclear layer in the peripheral retina in LIX was only thinner than those of D-CON and INS. In an early type 2 diabetic mouse model, lixisenatide treatment showed superior anti-inflammatory effects on the retina and optic nerve head independent of hyperglycemia. Thus, the neuroprotective effects of lixisenatide treatment in the peripheral inner nuclear layer should be evaluated in early type 2 diabetic retinopathy.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos/farmacologia , Retina/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2 , Retinopatia Diabética/patologia , Hipoglicemiantes , Camundongos
16.
Nature ; 581(7808): 278-282, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32433619

RESUMO

Human eyes possess exceptional image-sensing characteristics such as an extremely wide field of view, high resolution and sensitivity with low aberration1. Biomimetic eyes with such characteristics are highly desirable, especially in robotics and visual prostheses. However, the spherical shape and the retina of the biological eye pose an enormous fabrication challenge for biomimetic devices2,3. Here we present an electrochemical eye with a hemispherical retina made of a high-density array of nanowires mimicking the photoreceptors on a human retina. The device design has a high degree of structural similarity to a human eye with the potential to achieve high imaging resolution when individual nanowires are electrically addressed. Additionally, we demonstrate the image-sensing function of our biomimetic device by reconstructing the optical patterns projected onto the device. This work may lead to biomimetic photosensing devices that could find use in a wide spectrum of technological applications.


Assuntos
Materiais Biomiméticos , Biomimética/instrumentação , Compostos de Cálcio , Nanofios , Óxidos , Retina , Titânio , Desenho de Equipamento , Humanos , Robótica/instrumentação , Visão Ocular
17.
PLoS One ; 15(5): e0231677, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32421691

RESUMO

Retinal oximetry is an important screening tool for early detection of retinal pathologies due to changes in the vasculature and also serves as a useful indicator of human-body-wide vascular abnormalities. We present an automatic technique for the measurement of oxygen saturation in retinal arterioles and venules using dual-wavelength retinal oximetry images. The technique is based on segmenting an optic-disc-centered ring-shaped region of interest and subsequent analysis of the oxygen saturation levels. We show that the two dominant peaks in the histogram of the oxygen saturation levels correspond to arteriolar and venular oxygen saturations from which the arterio-venous saturation difference (AVSD) can be calculated. For evaluation, we use a normative database of Asian Indian eyes containing 44 dual-wavelength retinal oximetry images. Validations against expert manual annotations of arterioles and venules show that the proposed technique results in an average arteriolar oxygen saturation (SatO2) of 87.48%, venular SatO2 of 57.41%, and AVSD of 30.07% in comparison with the expert ground-truth average arteriolar SatO2 of 89.41%, venular SatO2 of 56.32%, and AVSD of 33.09%, respectively. The results exhibit high consistency across the dataset indicating that the automated technique is an accurate alternative to the manual procedure.


Assuntos
Oximetria/métodos , Vasos Retinianos/diagnóstico por imagem , Arteríolas/diagnóstico por imagem , Arteríolas/metabolismo , Feminino , Humanos , Masculino , Oxigênio/metabolismo , Consumo de Oxigênio , Retina/fisiologia , Vasos Retinianos/metabolismo , Vênulas/diagnóstico por imagem , Vênulas/metabolismo
18.
BMC Med Genet ; 21(1): 96, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381069

RESUMO

BACKGROUND: Joubert syndrome (JBTS) is a genetically heterogeneous group of neurodevelopmental syndromes caused by primary cilia dysfunction. Usually the neurological presentation starts with abnormal neonatal breathing followed by muscular hypotonia, psychomotor delay, and cerebellar ataxia. Cerebral MRI shows mid- and hindbrain anomalies including the molar tooth sign. We report a male patient with atypical presentation of Joubert syndrome type 23, thus expanding the phenotype. CASE PRESENTATION: Clinical features were consistent with JBTS already from infancy, yet the syndrome was not suspected before cerebral MRI later in childhood showed the characteristic molar tooth sign and ectopic neurohypophysis. From age 11 years seizures developed and after few years became increasingly difficult to treat, also related to inadequate compliance to therapy. He died at 23 years of sudden unexpected death in epilepsy (SUDEP). The genetic diagnosis remained elusive for many years, despite extensive genetic testing. We reached the genetic diagnosis by performing whole genome sequencing of the family trio and analyzing the data with the combination of one analysis pipeline for single nucleotide variants (SNVs)/indels and one for structural variants (SVs). This lead to the identification of the most common variant detected in patients with JBTS23 (OMIM# 616490), rs534542684, in compound heterozygosity with a 8.3 kb deletion in KIAA0586, not previously reported. CONCLUSIONS: We describe for the first time ectopic neurohypophysis and SUDEP in JBTS23, expanding the phenotype of this condition and raising the attention on the possible severity of the epilepsy in this disease. We also highlight the diagnostic power of WGS, which efficiently detects SNVs/indels and in addition allows the identification of SVs.


Assuntos
Anormalidades Múltiplas/genética , Proteínas de Ciclo Celular/genética , Cerebelo/anormalidades , Morte Súbita/patologia , Epilepsia/genética , Anormalidades do Olho/genética , Doenças Renais Císticas/genética , Retina/anormalidades , Anormalidades Múltiplas/mortalidade , Anormalidades Múltiplas/patologia , Adulto , Cerebelo/patologia , Criança , Morte Súbita/epidemiologia , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/mortalidade , Deficiências do Desenvolvimento/patologia , Epilepsia/mortalidade , Epilepsia/patologia , Anormalidades do Olho/mortalidade , Anormalidades do Olho/patologia , Feminino , Heterozigoto , Humanos , Mutação INDEL , Doenças Renais Císticas/mortalidade , Doenças Renais Císticas/patologia , Masculino , Neuro-Hipófise/metabolismo , Neuro-Hipófise/patologia , Retina/patologia , Sequenciamento Completo do Genoma , Adulto Jovem
19.
Eur J Ophthalmol ; 30(3): 586-594, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32347762

RESUMO

PURPOSE: To report 12-month outcomes of a Polish National Treatment Program using aflibercept and ranibizumab in eyes with wet, age-related macular degeneration in routine clinical practice. MATERIAL AND METHODS: This was a non-randomized, retrospective, observational multicenter study. Anonymous data contained in the electronic Therapeutic Program Monitoring System were utilized in this study. RESULTS: The study population consisted of 2828 eyes from 2718 patients. The median age was 76.0 [70.0, 81.0] years; 61.7% were female. Best corrected visual acuity increased from 58.86 [50.05, 69.95] letters to 65.1 [50.1, 73.9] letters (p < 0.001). The median change in best corrected visual acuity was 0.0 [-4.0, 12.2] letters: 2.9 [-2.9, 15.1] letters for treatment-naïve eyes and 0.0 [-4.0, 8.8] letters for those continuing treatment (p < 0.001). The median central retinal thickness was significantly reduced from 341.0 [281.0, 422.0] to 275.0 [221.0, 344.0] µm (p < 0.001). The median number of visits was 9.0 [8.0, 9.0]. The median number of injections was 7.0 [6.0, 8.0]: 8.0 [7.0, 8.0] for treatment-naïve eyes and 6.0 [5.0, 7.0] for those continuing treatment (p < 0.001). CONCLUSION: Eyes treated as part of the Polish therapeutic program gained functional stability and morphological improvement. Treatment-naïve eyes showed the greatest functional benefit.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/fisiopatologia , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Polônia , Retina/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/fisiopatologia
20.
Proc Natl Acad Sci U S A ; 117(16): 9001-9012, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32265282

RESUMO

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.


Assuntos
Evolução Molecular , Regulação da Expressão Gênica no Desenvolvimento , Sequências Reguladoras de Ácido Nucleico/genética , Retina/patologia , Doenças Retinianas/genética , Adulto , Animais , Análise Mutacional de DNA , Epigenômica , Feminino , Variação Genética , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Mutação , RNA-Seq , Retina/crescimento & desenvolvimento , Doenças Retinianas/patologia , Especificidade da Espécie
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