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1.
Eur J Pediatr ; 183(2): 885-895, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37864600

RESUMO

The purpose of the study was to determine the associations of self-perception, motor skills, and clinical features of young school-age children with glaucoma (CG). This is a cross-sectional observational study. Children from preschool to second grade, including CG (N = 19), children with amblyopia (CA, N = 28), and controls (N = 32), completed the Manual Dexterity and Aiming and Catching Scales of the Movement Assessment Battery for Children-2nd edition (MABC-2), including Manual Dexterity, Aiming and Catching, and Balance. CG, CA, and their parent completed the Pictorial Scale of Perceived Competence and Social Acceptance for Young Children, respectively, assessing the child's cognitive competence, peer acceptance, physical competence, and maternal acceptance. The Kruskal-Wallis H test and Bonferroni post hoc test compared motor skills among groups. Spearman's correlation analysis evaluated the correlations between motor skills, self-perception, and clinical features. The CG reported lower peer acceptance than CA (P = 0.040), and the parents of CG reported lower cognitive competence than CG reported (P = 0.046). Compared with controls, CG had worse performance of Aiming and Catching, and Balance (P = 0.018 and P = 0.001), and CA had worse performance of Balance (P = 0.009). The motor skills were comparable between CG and CA. For CG, older age correlated with worse competence of Aiming and Catching (r = - 0.620, P = 0.005), better best-corrected visual acuity of better-seeing eye correlated with higher competence of Manual Dexterity and Balance (r = - 0.494, P = 0.032, and r = - 0.516, P = 0.024), and longer duration of glaucoma correlated with worse competence of Manual Dexterity (r = - 0.487, P = 0.034). CONCLUSION:  Glaucoma and amblyopia have significant negative impacts on children's daily motor skills. The acuity of a better-seeing eye is an important factor influencing motor movement. TRIAL REGISTRATION: ClinicalTrials.gov identifier, ChiCTR2100050415. WHAT IS KNOWN: • The state of mental health in early childhood influences the development of their future personality and physical development. The prognosis and management of glaucoma may seriously impair the mental health development of the affected children. However, the exploration of psychological aspects and motor movement of childhood glaucoma was limited. WHAT IS NEW: • Children with glaucoma have impaired motor skills and self-perception development, especially in terms of peer socialization.


Assuntos
Ambliopia , Glaucoma , Percepção de Movimento , Criança , Humanos , Pré-Escolar , Ambliopia/psicologia , Estudos Transversais , Destreza Motora , Autoimagem , Glaucoma/diagnóstico
2.
Eur J Pediatr ; 183(4): 1891-1900, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38319404

RESUMO

Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment, and the increase in number and survival of premature infants may inflate its burden globally. We aimed to comprehensively assess the trends and inequalities in the burden of ROP-related visual impairment and to identify improvement gaps to facilitate appropriate actions in neonatal care systems. We obtained ROP data from the Global Burden of Disease 2019 study. We employed joinpoint regression analysis to assess the trends of the burden of ROP-related visual impairment, measured by age-standardised prevalence rates, health equity analysis methods to evaluate cross-country burden inequalities, and data envelopment and stochastic frontier analyses to identify improvement gaps based on the development status, i.e., sociodemographic index (SDI). Between 1990 and 2019, the age-standardised prevalence rates of ROP-related visual impairment significantly increased worldwide (average annual percentage change: 0.23 [95% confidence interval, 0.21-0.26] among males and 0.26 [0.25-0.27] among females), primarily in developed regions. Although significant SDI-related cross-country inequalities were identified, these reduced over time (slope index of inequality: -57.74 [-66.22 to -49.25] in 1990 to -29.68 [-38.39 to -20.97] in 2019; health concentration index: -0.11 [-0.13 to -0.09] in 1990 to -0.07 [-0.09 to -0.06] in 2019). Notably, some less-developed countries exhibited superior performance despite limited resources, whereas others with a higher SDI delivered lagging performance.  Conclusion: The global burden of ROP-related visual impairment has steadily increased between 1990 and 2019, with disproportionate burden concentration among less-developed countries, requiring appropriate preventive and intervention measures. What is Known: • Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment. • The prevalence of ROP is anticipated to increase due to the growing number of extremely premature infants. What is New: • The prevalence of ROP-related visual impairment has increased worldwide, primarily in developed regions, with declining but persisting cross-country inequalities. • The increasing burden of ROP-related visual impairment should be considered as part of global and national health agendas, requiring interventions with proven efficacy.


Assuntos
Doenças do Recém-Nascido , Retinopatia da Prematuridade , Recém-Nascido , Masculino , Lactente , Feminino , Humanos , Criança , Retinopatia da Prematuridade/complicações , Retinopatia da Prematuridade/epidemiologia , Países em Desenvolvimento , Lactente Extremamente Prematuro , Prevalência , Transtornos da Visão/epidemiologia , Transtornos da Visão/etiologia , Idade Gestacional
3.
Exp Eye Res ; 231: 109473, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37061115

RESUMO

N6-methyladenosine (m6A) modification is one of the most common types of methylation modifications in eukaryotic mRNA. However, its role in the pathogenesis of pseudoexfoliation glaucoma (PXG) has not yet been reported. To enhance understanding in this regard, we assessed the m6A methylome in the aqueous humor of patients with PXG. MeRIP-Seq and RNA-Seq analyses were performed to compare the m6A methylomes and gene expression profiles of the aqueous humor of patients with PXG with those of patients with age-related cataract (ARC). Colorimetric m6A quantification was performed to detect global m6A levels. Quantitative reverse transcription PCR confirmed the expression of m6A-related enzymes and mRNAs in both groups. Results showed significantly higher aqueous humor m6A levels in the PXG group than in the ARC group. Five m6A-related enzymes, including METTL3, YTHDC2, HNRNPA2B1, HNRNPC, and LRPPRC, were significantly up-regulated in PXG specimens. We also observed 9728 m6A-modified peaks related to 6126 gene transcripts in the PXG group, with more than 250 genes containing one m6A peak (hypomethylated or hypermethylated). The distribution of the m6A peaks was enriched in coding sequences and 3'-untranslated regions for both groups. GGAC motif structures were also significantly enriched. Bioinformatics analysis further revealed that m6A plays a critical role in extracellular matrix formation and histone deacetylation. Additionally, MMP14, ADAMTSL1, FN1, and HDAC1 showed significant changes in m6A methylation and mRNA expression in the PXG group. Therefore, m6A methylation may regulate extracellular matrix composition in PXG and METTL3 may be a pivotal regulator of this process. In the future, it would be necessary to investigate MMP14, ADAMTSL1, FN1, and HDAC1, which are potential target genes.


Assuntos
Catarata , Síndrome de Exfoliação , Glaucoma , Humanos , Transcriptoma , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 14 da Matriz/metabolismo , Metilação , Humor Aquoso/metabolismo , Síndrome de Exfoliação/metabolismo , Catarata/genética , Catarata/metabolismo , Glaucoma/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Metiltransferases/genética
4.
Exp Eye Res ; 233: 109545, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37406955

RESUMO

PURPOSE: To characterize the distribution of refractive and ocular biometry parameters and analyze the effect factors of the refractive status in cynomolgus monkey colonies. METHODS: A Population-based cross-sectional study was conducted in adult cynomolgus macaque colonies. Animals were anesthetized with Zoletil 50. Intraocular pressure was measured using the Icare tonometer. Cycloplegic refraction (three drops of 1% tropicamide) and corneal radius of curvature (CRC) were measured using an autorefractor. The spherical equivalent (SE) was calculated. Biometric measurements, including the anterior chamber depth (ACD), lens thickness (LT), and axial length (AL), were obtained by A-scan ultrasonography. The AL-to-CR ratio (AL/CRC) was calculated. Central corneal thickness (CCT) and choroidal thickness (ChT) were measured using the Heidelberg Spectralis HRA OCT. Multiple regression analysis was performed to explore the association between refraction and ocular biometry. RESULTS: Among 263 cynomolgus monkeys (aged 5-26 years), which consisted of 520 eyes, 29.42% had hyperopia, 27.12% had emmetropia, 33.27% had mild-to-moderate myopia and 10.19% had high myopia. The mean SE was -1.27 ± 3.44 Diopters (D). The mean CRC, CCT, AL, and ChT was 5.70 ± 0.22 mm, 454.30 ± 32.40 µm, 18.76 ± 0.89 mm and 188.96 ± 38.19 µm, respectively. The LT was the thickest in the hyperopic eyes. CRC was the lowest, and CCT was the thickest in high myopic eyes. AL increased, while ChT decreased as SE decreased. For the SE variance, AL alone explained 40.5%; age, AL, and CRC together explained 57.5%. CONCLUSIONS: The refractive characteristics and biometry parameters of cynomolgus monkeys are highly comparable to those of humans. AL, CRC, and ChT showed the similar variation tendency in cynomolguses when compared to humans. Cynomolgus monkeys with naturally-occurring refractive errors may be a good animal model for refractive studies.


Assuntos
Hiperopia , Miopia , Adulto , Humanos , Animais , Macaca fascicularis , Estudos Transversais , Refração Ocular , Córnea/diagnóstico por imagem , Biometria
5.
Int J Med Sci ; 20(10): 1363-1376, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37786442

RESUMO

Repeated low-level red-light (RLRL), characterized by increased energy supply and cellular metabolism, thus enhancing metabolic repair processes, has gained persistent worldwide attention in recent years as a new novel scientific approach for therapeutic application in myopia. This therapeutic revolution led by RLRL therapy is due to significant advances in bioenergetics and photobiology, for instance, enormous progresses in photobiomodulation regulated by cytochrome c oxidase, the primary photoreceptor of the light in the red to near infrared regions of the electromagnetic spectrum, as the primary mechanism of action in RLRL therapy. This oxidase is also a key mitochondrial enzyme for cellular bioenergetics, especially for the nerve cells in the retina and brain. In addition, dopamine (DA)-enhanced release of nitric oxide may also be involved in controlling myopia by activation of nitric oxide synthase, enhancing cGMP signaling. Recent evidence has also suggested that RLRL may inhibit myopia progression by inhibiting spherical equivalent refraction (SER) progression and axial elongation without adverse effects. In this review, we provide scientific evidence for RLRL therapy as a unique paradigm to control myopia and support the theory that targeting neuronal energy metabolism may constitute a major target for the neurotherapeutics of myopia, with emphasis on its molecular, cellular, and nervous tissue levels, and the potential benefits of RLRL therapy for myopia.


Assuntos
Terapia com Luz de Baixa Intensidade , Miopia , Humanos , Miopia/tratamento farmacológico , Retina/metabolismo , Refração Ocular , Dopamina/metabolismo
6.
Int J Med Sci ; 20(1): 50-56, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36619230

RESUMO

Objective: To evaluate the effects of long-term wear and discontinuation of the orthokeratology lenses (Orth-K) on the biological parameters of eyeballs in children with myopia. Methods: In this prospective study, a total of 308 subjects with myopia were randomized to receive Orth-K (n = 154) or single vision spectacles (SVS) (n = 154) for 12 months followed by a 1-month withdrawal period. The axial length (AL), the central corneal thickness (CCT), the anterior chamber depth (ACD) and the central lens thickness (CLT) were assessed at the baseline, 6 months, 12 months, and 13 months (1-month after lens withdrawal). Results: A total of 279 subjects completed the 13-month follow-up (142 in Orth-K group and 137 in SVS group). No statistical difference was noted in AL, CCT, ACD and CLT between the two groups at the baseline (all p > 0.05). However, compared with the baseline, the AL from the two groups became elongated 12 months after wearing Orth-K or SVS. The increase of AL in Orth-K group was 0.22 ± 0.11 mm, significantly smaller than 0.35 ± 0.08 mm in SVS group (p < 0.05). In addition, CCT in Orth-K group was 544.26 ± 11.69 µm at 12 months, significantly thinner than 550.49 ± 12.13 µm in SVS group (p < 0.05). Interestingly, the change in CCT between the baseline and 1-month after withdrawal of the lens was not statistically different in either group (all p > 0.05). Furthermore, at 12-months, CLT in Orth-K group was 3.35 ± 0.21 mm, significantly thicker than 3.31 ± 0.15 mm at baseline and thicker than 3.30 ± 0.05 mm in SVS group at 12 months (all p < 0.05). Lastly, ACD was not statistically different between Orth-K and SVS groups at any time point (p > 0.05). Conclusion: Orthokeratology lenses can effectively retard axial elongation, reversibly reduce CCT, increase CLT in myopic children, but have no obvious effect on ACD, indicating that Orth-K may significantly retard myopia without noticeable myopia rebound after interruption of Orth-K.


Assuntos
Miopia , Humanos , Criança , Estudos Prospectivos , Miopia/terapia , Refração Ocular
7.
BMC Ophthalmol ; 23(1): 53, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36750922

RESUMO

PURPOSE: To describe the normative profile of ophthalmic parameters in a healthy cynomolgus monkey colony, and to identify the characteristic of the spontaneous ocular disease non-human primates (NHP) models. METHODS: The NHP eye study was a cross-sectional on-site ocular examination with about 1,000 macaques held in Guangdong Province, southeastern China. The NHPs (Macaca fascicularis, cynomolgus) in this study included middle-aged individuals with a high prevalence of the ocular disease. The NHP eye study (NHPES) performed the information including systematic data and ocular data. Ocular examination included measurement of intraocular pressure (IOP), anterior segment- optical coherence tomography (OCT), slit-lamp examination, fundus photography, autorefraction, electroretinography, etc. Ocular diseases included measurement of refractive error, anisometropia, cataract, pterygium, etc. RESULTS: A total of 1148 subjects were included and completed the ocular examination. The average age was 16.4 ± 4.93 years. Compared to the male participants, the females in the NHPES had shorter axial length and the mean Average retinal nerve fiber layer (RNFL) thickness (except for the nasal quadrants). The mean IOP, anterior chamber depth, lens thickness, axial length, central corneal thickness, choroid thickness and other parameters were similar in each group. CONCLUSION: The NHPES is a unique and high-quality study, this is the first large macaque monkey cohort study focusing on ocular assessment along with comprehensive evaluation. Results from the NHPES will provide important information about the normal range of ophthalmic measurements in NHP.


Assuntos
Retina , Células Ganglionares da Retina , Feminino , Animais , Masculino , Macaca fascicularis , Estudos de Coortes , Estudos Transversais , Tomografia de Coerência Óptica/métodos
8.
Ophthalmic Res ; 66(1): 1406-1416, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37926084

RESUMO

INTRODUCTION: The primary aim of this study was to assess the longitudinal changes in retinal nerve fiber layer (RNFL) thickness and relative ONH parameters using spectral-domain optical coherence tomography (SD-OCT) in the living eyes of nonhuman primates with spontaneous glaucoma. METHODS: Totally 9 macaque subjects underwent a standard fundus photo and OCT examination, including 3 adult monkeys with stable elevated intraocular pressure (IOP) as the glaucoma suspect group and 6 normal IOP monkeys as the control group. Each eye of primates with IOP measurement was repeated three times. OCT measurements recorded RNFL, Bruch's membrane opening (BMO) minimum rim width (MRW). The follow-up scan of glaucomatous subjects was undergone in 10 months. RESULTS: The mean ages of glaucoma and healthy subjects are 19.33 ± 0.33 and 20.5 ± 1.46 years. Elevated IOP was achieved in three nonhuman primate eyes with an average increase of 10 mm Hg over the study period. Elevated IOP was associated with decreased RNFL thickness in all the regions and decreased RNFL phase retardation in the superior and inferior regions. When averaged over the entire retinal area, only the whole RNFL and temporal regions showed a significant decrease. The mean IPL thicknesses are 87.17 ± 2.15 µm in glaucomatous and 93.33 ± 1.51 µm in healthy eyes (p = 0.03). Lamina cribrosa parameters are measured from the OCT images and showed significant differences between glaucoma primates and normal primates. CONCLUSIONS: Of the measured parameters, decreased RNFL and MRW were correlated with glaucomatous damage. Natural glaucoma primate can be a natural glaucoma model which is closer to glaucoma in humans.


Assuntos
Glaucoma , Hipertensão Ocular , Disco Óptico , Adulto , Animais , Humanos , Adolescente , Adulto Jovem , Pressão Intraocular , Células Ganglionares da Retina , Glaucoma/diagnóstico , Hipertensão Ocular/diagnóstico , Tomografia de Coerência Óptica/métodos , Primatas
9.
J Med Internet Res ; 25: e39507, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36857115

RESUMO

BACKGROUND: Patients with high myopia have an increased lifetime risk of complications. The prevalence patterns of high myopia in children and adolescents in southern China are unclear. Early identification of high-risk individuals is critical for reducing the occurrence and development of high myopia and avoiding the resulting complications. OBJECTIVE: This study aimed to determine the prevalence of high myopia in children and adolescents in southern China via real-world screening data and to predict its onset by studying the risk factors for high myopia based on machine learning. METHODS: This retrospective school-based study was conducted in 13 cities with different gross domestic products in southern China. Through data acquisition and filtering, we analyzed the prevalence of high myopia and its association with age, school stage, gross domestic product, and risk factors. A random forest algorithm was used to predict high myopia among schoolchildren and then assessed in an independent hold-out group. RESULTS: There were 1,285,609 participants (mean age 11.80, SD 3.07, range 6-20 years), of whom 658,516 (51.2%) were male. The overall prevalence of high myopia was 4.48% (2019), 4.88% (2020), and 3.17% (2021), with an increasing trend from the age of 11 to 17 years. The rates of high myopia increased from elementary schools to high schools but decreased at all school stages from 2019 to 2021. The coastal and southern cities had a higher proportion of high myopia, with an overall prevalence between 2.60% and 5.83%. Age, uncorrected distance visual acuity, and spherical equivalents were predictive factors for high myopia onset in schoolchildren. The random forest algorithm achieved a high accuracy of 0.948. The area under the receiver operator characteristic curve (AUC) was 0.975. Both indicated sufficient model efficacy. The performance of the model was validated in an external test with high accuracy (0.971) and a high AUC (0.957). CONCLUSIONS: High myopia had a high incidence in Guangdong Province. Its onset in children and adolescents was well predicted with the random forest algorithm. Efficient use of real-world data can contribute to the prevention and early diagnosis of high myopia.


Assuntos
Miopia , Humanos , Adolescente , Criança , Masculino , Adulto Jovem , Adulto , Feminino , Prevalência , Estudos Retrospectivos , China , Cidades
10.
J Neuroinflammation ; 19(1): 261, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36289494

RESUMO

BACKGROUND: The aim of this study was to establish a complete retinal cell atlas of ischemia-reperfusion injury by single-cell RNA sequencing, and to explore the underlying mechanism of retinal ischemia-reperfusion injury in mice. METHODS: Single-cell RNA sequencing was used to evaluate changes in the mouse retinal ischemia reperfusion model. In vivo and in vitro experiments were performed to verify the protective effect of inhibiting ferroptosis in retinal ischemia-reperfusion injury. RESULTS: After ischemia-reperfusion injury, retinal cells were significantly reduced, accompanied by the activation of myeloid and a large amount of blood-derived immune cell infiltration. The IFNG, MAPK and NFKB signaling pathways in retinal neuronal cells, together with the TNF signaling pathway in myeloid give rise to a strong inflammatory response in the I/R state. Besides, the expression of genes implicating iron metabolism, oxidative stress and multiple programed cell death pathways have changed in cell subtypes described above. Especially the ferroptosis-related genes and blocking this process could apparently alleviate the inflammatory immune responses and enhance retinal ganglion cells survival. CONCLUSIONS: We established a comprehensive landscape of mouse retinal ischemia-reperfusion injury at the single-cell level, revealing the important role of ferroptosis during this injury, and targeted inhibition of ferroptosis can effectively protect retinal structure and function.


Assuntos
Ferroptose , Traumatismo por Reperfusão , Camundongos , Animais , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Modelos Animais de Doenças , Isquemia , Análise de Sequência de RNA , Ferro
11.
Stem Cells ; 39(3): 280-295, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33373496

RESUMO

Quiescence and self-renewal of human corneal epithelial progenitor/stem cells (LEPC) are regulated by the limbal niche, presumably through close interaction with limbal (stromal) niche cells (LNC). Paired box homeotic gene 6 (Pax6), a conserved transcription factor essential for eye development, is essential for proper differentiation of limbal and corneal epithelial stem cells. Pax6 haploinsufficiency causes limbal stem cell deficiency, which leads to subsequent corneal blindness. We previously reported that serial passage of nuclear Pax6+ LNC resulted in the gradual loss of nuclear Pax6+ and neural crest progenitor status, the latter of which was reverted upon recovery of Pax6. These findings suggest Pax6 plays a pivotal role in supporting the self-renewal of LEPC in limbal niche. Herein, we show that HC-HA/PTX3, a unique matrix purified from amniotic membrane (AM) and consists of heavy chain 1of inter-α-trypsin inhibitor covalently linked to hyaluronic acid and complexed with pentraxin 3, is capable of reverting senescent LNC to nuclear Pax6+ neural crest progenitors that support self-renewal of LEPC. Such reversion is causally linked to early cell aggregation mediated by activation of C-X-C chemokine receptor type 4 (CXCR4)-mediated signaling followed by activation of bone morphogenetic protein (BMP) signaling. Furthermore, CXCR4-mediated signaling, but not BMP signaling, controls recovery of the nuclear Pax6+ neural crest progenitors. These findings not only explain why AM helps in vivo and ex vivo expansion of human LEPC, but they also illuminate the potential role of HC-HA/PTX3 as a surrogate matrix niche that complements stem cell-based therapies in regenerative medicine.


Assuntos
Proteína C-Reativa/metabolismo , Limbo da Córnea/citologia , Fator de Transcrição PAX6/metabolismo , Componente Amiloide P Sérico/metabolismo , Nicho de Células-Tronco/fisiologia , Idoso , Diferenciação Celular/fisiologia , Células Cultivadas , Doenças da Córnea/genética , Células Epiteliais/metabolismo , Epitélio Corneano/citologia , Humanos , Pessoa de Meia-Idade , Crista Neural/citologia , Células-Tronco/metabolismo
12.
Mol Ther ; 29(4): 1639-1657, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33388417

RESUMO

Glaucoma is the leading cause of irreversible vision loss, affecting more than 70 million individuals worldwide. Circulatory disturbances of aqueous humor (AH) have long been central pathological contributors to glaucomatous lesions. Thus, targeting the AH outflow is a promising approach to treat glaucoma. However, the epigenetic mechanisms initiating AH outflow disorders and the targeted treatments remain to be developed. Studying glaucoma patients, we identified GDF7 (growth differentiation factor 7) hypomethylation as a crucial event in the onset of AH outflow disorders. Regarding the underlying mechanism, the hypomethylated GDF7 promoter was responsible for the increased GDF7 production and secretion in primary open-angle glaucoma (POAG). Excessive GDF7 protein promoted trabecular meshwork (TM) fibrosis through bone morphogenetic protein receptor type 2 (BMPR2)/Smad signaling and upregulated pro-fibrotic genes, α-smooth muscle actin (α-SMA) and fibronectin (FN). GDF7 protein expression formed a positive feedback loop in glaucomatous TM (GTM). This positive feedback loop was dependent on the activated TET (ten-eleven translocation) enzyme, which kept the GDF7 promoter region hypomethylated. The phenotypic transition in TM fortified the AH outflow resistance, thus elevating the intraocular pressure (IOP) and attenuating the nerve fiber layer. This methylation-dependent mechanism is also confirmed by a machine-learning model in silico with a specificity of 84.38% and a sensitivity of 89.38%. In rhesus monkeys, we developed GDF7 neutralization therapy to inhibit TM fibrosis and consequent AH outflow resistance that contributes to glaucoma. The neutralization therapy achieved high-efficiency control of the IOP (from 21.3 ± 0.3 to 17.6 ± 0.2 mmHg), a three-fold improvement in the outflow facility (from 0.1 to 0.3 µL/min · mmHg), and protection of nerve fibers. This study provides new insights into the epigenetic mechanism of glaucoma and proposes an innovative GDF7 neutralization therapy as a promising intervention.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Proteínas Morfogenéticas Ósseas/genética , Fibrose/terapia , Glaucoma de Ângulo Aberto/terapia , Fatores de Diferenciação de Crescimento/genética , Actinas/genética , Animais , Humor Aquoso/metabolismo , Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Metilação de DNA/genética , Modelos Animais de Doenças , Fibrose/genética , Fibrose/patologia , Glaucoma de Ângulo Aberto/genética , Glaucoma de Ângulo Aberto/patologia , Fatores de Diferenciação de Crescimento/antagonistas & inibidores , Humanos , Macaca mulatta/genética , Oxigenases de Função Mista/genética , Proteínas Proto-Oncogênicas/genética , Transdução de Sinais/genética , Proteínas Smad/genética , Malha Trabecular/metabolismo , Malha Trabecular/patologia
13.
Ophthalmic Res ; 65(3): 342-350, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35272293

RESUMO

INTRODUCTION: The aim of this study was to investigate the long-term visual outcomes and factors associated with vision loss in Chinese patients with primary congenital glaucoma (PCG) after successful intraocular pressure (IOP) control (IOP ≤21 mm Hg). METHODS: PCG patients with IOP control who were examined in the glaucoma clinic at Zhongshan Ophthalmic Center from 2019 to 2020 were enrolled. The final visual outcome was evaluated by the best corrected visual acuity (VA). Univariate and multivariate analyses were used to investigate the associations of visual impairment with potential risk factors. The causes for decreased VA (<20/50) were also analyzed. RESULTS: Fifty-nine patients (95 eyes) were included in the cohort, with a mean age of 8.7 years. The mean logMAR VA was 0.62 ± 0.64. The VAs of eyes treated for PCG were good (≥20/50) in 56%, fair (20/60-20/200) in 30%, and poor (<20/200) in 14%. The most common cause of decreased VA was amblyopia (64.3%). Multivariate logistic regression analysis showed that undergoing multiple surgeries (OR: 4.86, 95% CI: 1.11-21.16, p = 0.035) was significantly associated with visual impairment. CONCLUSION: The results showed that good VA was attainable in approximately half of PCG eyes under IOP control. Prompt and effective treatment of PCG, management of amblyopia and ocular comorbidities may be potential steps toward achieving good visual outcomes in PCG patients.


Assuntos
Ambliopia , Glaucoma , Trabeculectomia , Criança , Seguimentos , Glaucoma/complicações , Glaucoma/epidemiologia , Humanos , Pressão Intraocular , Estudos Retrospectivos , Trabeculectomia/métodos , Resultado do Tratamento , Transtornos da Visão/epidemiologia , Transtornos da Visão/etiologia , Acuidade Visual
14.
Int J Med Sci ; 18(1): 109-119, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390779

RESUMO

Near infrared (NIR) light therapy, or photobiomodulation therapy (PBMT), has gained persistent worldwide attention in recent years as a new novel scientific approach for therapeutic applications in ophthalmology. This ongoing therapeutic adoption of NIR therapy is largely propelled by significant advances in the fields of photobiology and bioenergetics, such as the discovery of photoneuromodulation by cytochrome c oxidase and the elucidation of therapeutic biochemical processes. Upon transcranial delivery, NIR light has been shown to significantly increase cytochrome oxidase and superoxide dismutase activities which suggests its role in inducing metabolic and antioxidant beneficial effects. Furthermore, NIR light may also boost cerebral blood flow and cognitive functions in humans without adverse effects. In this review, we highlight the value of NIR therapy as a novel paradigm for treatment of visual and neurological conditions, and provide scientific evidence to support the use of NIR therapy with emphasis on molecular and cellular mechanisms in eye diseases.


Assuntos
Oftalmopatias/terapia , Terapia com Luz de Baixa Intensidade/métodos , Apoptose/efeitos da radiação , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Oftalmopatias/patologia , Humanos , Terapia com Luz de Baixa Intensidade/instrumentação , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/efeitos da radiação , Células Fotorreceptoras de Vertebrados/citologia , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/efeitos da radiação , Superóxido Dismutase/metabolismo , Resultado do Tratamento
15.
Int J Med Sci ; 18(12): 2493-2499, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104080

RESUMO

Purpose: The anatomical parameters of normal lacrimal puncta and vertical canaliculus using optical coherence tomography (OCT) and the OCT imaging features of punctal lesions were analyzed to provide a basis for clinical diagnosis and treatment. Methods: From June to September 2019, 40 volunteers (80 eyes) from Tongji Hospital were enrolled. The external punctal diameter (ELP) was measured using slit-lamp microscopy and OCT. The internal lacrimal punctal diameter (ILP) at 100 µm, vertical canalicular length (VCL), and tear meniscus depth were measured by OCT with open eyes. Twenty-eight volunteers (56 eyes) underwent the same examinations with their eyes closed. The OCT imaging features of 26 patients (27 eyes) with lacrimal lesions were examined. Results: The ELP of the right and left healthy eyes under slit-lamp microscopy were 564.40 and 555.40 µm respectively. Under OCT, the ELP, ILP, and VCL of the right and left eyes were 628.20 um and 616.85 µm, 343.40 µm and 346.95 µm, 731.95 um and 709.20 µm respectively. The ELP was larger when measured by OCT than slit-lamp microscopy (p<0.05). Twenty-eight volunteers (56 eyes) had measurements taken under different conditions. The ELP, ILP, and VCL of the open and closed right eyes were 667.54 and 567.21 µm, 369.18 and 303.18 µm, 715.00 and 417.14 µm, respectively. The ELP, ILP, and VCL of the open and closed left eyes were 655.86 um and 551.68 µm, 369.25 um and 313.54 µm, 719.96 um and 433.89 µm respectively. The anatomical parameters of the open eyes were greater than those of the closed eyes (p<0.05). Thus, we identified the imaging features of lacrimal stenosis, punctal obstruction, punctal tear, lacrimal atresia, and lacrimal mass using OCT. Conclusions: OCT can be used to measure the anatomical parameters of lacrimal puncta and vertical canaliculus in vivo. In addition, OCT can detect punctal lesions in vivo and provide an objective basis for the clinical diagnosis and treatment of punctal lesions.


Assuntos
Aparelho Lacrimal/anatomia & histologia , Tomografia de Coerência Óptica , Adulto , Idoso , Estudos de Viabilidade , Feminino , Voluntários Saudáveis , Humanos , Aparelho Lacrimal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Microscopia com Lâmpada de Fenda , Adulto Jovem
16.
BMC Pregnancy Childbirth ; 21(1): 496, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238233

RESUMO

BACKGROUND: We aimed to evaluate the clinical value of copy number variation-sequencing (CNV-Seq) in combination with cytogenetic karyotyping in prenatal diagnosis. METHODS: CNV-Seq and cytogenetic karyotyping were performed in parallel for 9452 prenatal samples for comparison of the diagnostic performance of the two methods, and to evaluate the screening performance of maternal age, maternal serum screening, fetal ultrasound scanning and noninvasive prenatal testing (NIPT) for fetal pathogenic copy number variation (CNV). RESULTS: Among the 9452 prenatal samples, traditional karyotyping detected 704 cases (7.5%) of abnormal cytogenetic karyotypes, 171 (1.8%) chromosome polymorphism, 20 (0.2%) subtle structural variations, 74 (0.7%) mutual translocation (possibly balanced), 52 (0.6%) without karyotyping results, and 8431 (89.2%) normal cytogenetic karyotypes. Among the 8705 cases with normal karyotype, polymorphism, mutual translocation, or marker chromosome, CNV-Seq detected 63 cases (0.7%) of pathogenic chromosome microdeletion/duplication. Retrospectively, noninvasive prenatal testing (NIPT) had high sensitivity and specificity for the screening of fetal pathogenic CNV, and NIPT combining with maternal age, maternal serum screening or fetal ultrasound scanning, which improved the screening performance. CONCLUSION: The combined application of cytogenetic karyotyping and CNV-Seq significantly improved the detection rate of fetal pathogenic chromosome microdeletion/duplication. NIPT was recommended for the screening of pathogenic chromosome microdeletion/duplication, and NIPT combining with other screening methods further improved the screening performance for pathogenic fetal CNV.


Assuntos
Transtornos Cromossômicos/diagnóstico , Variações do Número de Cópias de DNA , Cariotipagem/estatística & dados numéricos , Diagnóstico Pré-Natal/estatística & dados numéricos , Análise de Sequência de DNA/estatística & dados numéricos , Adulto , Transtornos Cromossômicos/embriologia , Análise Citogenética , Feminino , Humanos , Idade Materna , Testes para Triagem do Soro Materno/estatística & dados numéricos , Teste Pré-Natal não Invasivo/métodos , Teste Pré-Natal não Invasivo/estatística & dados numéricos , Gravidez , Diagnóstico Pré-Natal/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassonografia Pré-Natal/estatística & dados numéricos
17.
Inorg Chem ; 59(4): 2575-2583, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32027494

RESUMO

Polyoxometalates (POMs)-porphyrin hybrids can serve as multifunctional materials with fascinating photocatalytic and photovoltaic properties. However, most previous POM-porphyrin hybrids are synthesized relied on electrostatic interactions to form ion pairs, which is not stable enough and subject to leaching and poor electronic communication. To our knowledge, no specific crystalline structure of direct covalently tris-functionalized POM-porphyrin hybrids has been identified. Herein, we discover an unprecedented polyoxometalates (POMs)-based photoresponsive cluster, {V6O13[ZnC61H58N5O4]2}2- (denoted as V6-Zn-2Por), which can be synthesized by covalently grafting two tris-functionalized Zn-porphyrin ligands onto Lindqvist-type hexavanadate cluster using decavanadates (TBA)3[H3V10O28] (denoted as V10, TBA = tetrabutylammonium cation) as precursor. Additionally, using tetraphenyl phosphonium as counterion, for the first time, a high-quality single crystal structure of the hybrid hexavanadate-porphyrin molecule is uncovered. Interestingly, the fluorescence emission spectra show that the fluorescence intensity of the organic-inorganic hybrid is partly quenched compared to pristine porphyrins, indicating possible energy/electron transfer between POMs cluster and porphyrin under light irradiation. Their UV-vis diffuse reflectance spectra show an extended absorption in the visible-light range. Finally, the as-prepared photoresponsive hexavanadate-porphyrin molecule is proved to exhibit effective photocatalytic activity toward removal of rhodamine B (an organic dye) under visible-light illumination.

18.
Int J Med Sci ; 17(13): 2024-2030, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32788881

RESUMO

To evaluate the efficacy of trabeculo-canalectomy in treating glaucoma patients, a retrospective investigation of 53 glaucoma patients (53 eyes) who underwent trabeculo-canalectomy was conducted at the First Affiliated Hospital of Nanjing Medical University, China, from April 2017 to January 2019. Intraocular pressure (IOP), visual acuity, surgical success rates, medications, and complications were monitored at post-operative 1 day, 1 week, 1, 3, 6, 12 and 24 months. Surgical success criteria were defined as 6 mm Hg≤IOP≤21 mmHg with or without additional medications. Our results showed that average IOP was statistically significant between pre-operative visit and each follow-up visit (all P <0.05). The total success rate of trabeculo-canalectomy at 1, 3, 6, 12 and 24 months was 92.5%, 86.8%, 94.3%, 92.5% and 90.6% respectively. After 3 months post-operatively, all patients had no obvious filtering blebs. The main early complications included postoperative hyphema (7.5%), elevated IOP (5.7%) and anterior chamber exudation (3.8%), which were all cured after conservative treatment. No blebitis, shallow anterior chamber, choroidal detachment and endophthalmitis were observed. Logistic regression analysis showed that patients with secondary glaucoma were more likely to undergo surgical failure 24 months post-operatively (P= 0.008). Thus, we conclude that trabeculo-canalectomy is effective and safe for the treatment of glaucoma.


Assuntos
Glaucoma/cirurgia , Trabeculectomia/métodos , Adulto , Idoso , Povo Asiático , Feminino , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual
19.
Int J Med Sci ; 17(8): 1095-1101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32410839

RESUMO

Colorectal cancer is the third common cancer in this world, accounting for more than 1 million cases each year. However, detailed etiology and mechanism of colorectal cancer have not been fully understood. For example, cyclooxygenase-2 (COX-2) and its product prostaglandin E2 (PGE2) have been closely linked to its occurrence, progression and prognosis. However, the mechanisms on how COX-2 and PGE2-mediate the pathogenesis of colorectal cancer are obscure. In this review, we have summarized recent advances in studies of pathogenesis and control in colorectal cancer to assist further advances in the research for the cure of the cancer. In addition, the knowledge gained may also guide the audiences for reduction of the risk and control of this deadly disease.


Assuntos
Carcinogênese/patologia , Neoplasias Colorretais/patologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Animais , Biópsia , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/patologia , Colo/citologia , Colo/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/epidemiologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Modelos Animais de Doenças , Progressão da Doença , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/patologia , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Prognóstico , Reto/citologia , Reto/patologia , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
20.
Int J Med Sci ; 17(6): 734-744, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32218695

RESUMO

We aimed to investigate the in vitro effect of pirfenidone (PFD) on proliferation, migration and collagen contraction of human pterygium fibroblasts (HPFs). HPFs were obtained from tissue explants during pterygium surgery. After treatment with pirfenidone, the HPFs proliferation was measured by MTT, cell cycle progression measured by flow cytometry, cell migration measured by the scratch assay, and cell contractility evaluated in fibroblast-populated collagen gels. The expression of TGF-ß1, TGF-ß2, MMP-1 and TIMP-1 were also determined with quantitative PCR, western blot and immunofluorescence staining. Results showed pirfenidone markedly inhibited HPFs proliferation with an IC50 of approximately 0.2 mg/ml. After treatment with 0.2 mg/ml pirfenidone for 24 hours, HPFs were at G0/G1 cell cycle arrest, with significantly reduced cell migration capability and collagen contraction, decreased mRNA and protein expressions of TGF-ß1, TGF-ß2 and MMP-1, and no alterations of TIMP-1 expression. Thus, we have concluded that pirfenidone at 0.2 mg/ml inhibits proliferation, migration, and collagen contraction of HPFs, which is associated with decreased expression of TGF-ß and MMP-1, and pirfenidone might represent a potentially therapeutic agent to prevent the recurrence of pterygium after surgery.


Assuntos
Fibrose/tratamento farmacológico , Metaloproteinase 1 da Matriz/genética , Pterígio/tratamento farmacológico , Piridonas/farmacologia , Fator de Crescimento Transformador beta1/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibrose/genética , Fibrose/patologia , Fibrose/cirurgia , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Pterígio/genética , Pterígio/patologia , Pterígio/cirurgia , Inibidor Tecidual de Metaloproteinase-1/genética , Fator de Crescimento Transformador beta2/genética
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