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Alzheimer's disease, one of the most common neurodegenerative diseases, is pathologically characterized by Amyloid beta containing plaques and neurofibrillary tangles. Amyloid beta (Aß) induces neuronal apoptosis through the intracellular Ca2+ increase, subsequent hyperactivation of cyclin-dependent kinase 5 (Cdk5) and mitochondrial abnormality. Recently, Cdk5 was identified as an upstream regulator of mitochondrial fission during neuronal apoptosis, but the underlying mechanism remains unclear. Here, in vitro phosphorylation assays showed that Cdk5 could phosphorylate the recombinant Drp1 at Serine 579. Aß1-42 stimulation increased the phosphorylation level of Drp1 at Serine 579 in mouse cortical neurons. Cdk5 inhibitor roscovitine and knockdown of Cdk5 by a lentiviral vector expressing shRNA targeting Cdk5 (Lenti-Cdk5-shRNA) efficiently prevented Aß1-42 induced Drp1 phosphorylation in neurons. In addition, Aß1-42 stimulation induced markedly mitochondrial fission in neurons. Roscovitine, Lenti-Cdk5-shRNA and expression of phospho-defect mutatant GFP-Drp1-S579A in neurons attenuated Aß1-42 induced mitochondrial fission, whereas expression of phospho-mimetic mutant GFP-Drp1-S579D alone resulted in mitochondiral fission similar to Aß1-42 stimulation. Moreover, Roscovitine and Lenti-Cdk5-shRNA suppressed the cleavage of caspase-3 and protected neurons against Aß1-42 induced neuronal apoptosis.Thus, our data indicate that Drp1 is a direct target of Cdk5, and Cdk5-mediated phosphorylation of Drp1 at Serine 579 regulates Aß1-42 induced mitochondrial fission and neuronal toxicity.
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Peptídeos beta-Amiloides/metabolismo , Apoptose , Quinase 5 Dependente de Ciclina/metabolismo , Dinaminas/metabolismo , Dinâmica Mitocondrial , Neurônios/metabolismo , Fragmentos de Peptídeos/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Animais , Quinase 5 Dependente de Ciclina/genética , Dinaminas/genética , Humanos , Camundongos , Neurônios/patologia , Fragmentos de Peptídeos/genética , Fosforilação/genéticaRESUMO
BACKGROUND: BHLHB5, an OLIG-related basic helix-loop-helix transcription factor, is required for the development of a subset of gamma-amino butyric acid-releasing (GABAergic) amacrine cells and OFF-cone bipolar (CB) cells in mouse retinas. In order to determine BHLHB5's functional mechanism in retinogenesis, we used the Cre-loxP recombination system to genetically trace the lineage of BHLHB5+ cells in normal and Bhlhb5-null retinas. The Bhlhb5-Cre knock-in allele was used to activate the constitutive expression of a GFP reporter in the Bhlhb5-expressing cells, and the cell fates of Bhlhb5-lineage cells were identified by using specific cell markers and were compared between normal and Bhlhb5-null retinas. RESULTS: In addition to GABAergic amacrine and OFF-CB cells, Bhlhb5 lineage cells give rise to ganglion, glycinergic amacrine, rod bipolar, ON-bipolar, and rod photoreceptor cells during normal retinal development. Targeted deletion of Bhlhb5 resulted in the loss of GABAergic amacrine, glycinergic amacrine, dopaminergic amacrine, and Type 2 OFF-CB cells. Furthermore, in the absence of BHLHB5, a portion of Bhlhb5 lineage cells switch their fate and differentiate into cholinergic amacrine cells. CONCLUSIONS: Our data reveal a broad expression pattern of Bhlhb5 throughout retinogenesis and demonstrate the cell-autonomous as well as non-cell-autonomous role of Bhlhb5 in the specification of amacrine and bipolar subtypes.
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Células Amácrinas/fisiologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Diferenciação Celular/fisiologia , Retina/citologia , Células Bipolares da Retina/fisiologia , Células Amácrinas/metabolismo , Animais , Diferenciação Celular/genética , Proteínas de Fluorescência Verde , Técnicas Histológicas , Imuno-Histoquímica , Camundongos , Retina/crescimento & desenvolvimento , Células Bipolares da Retina/metabolismoRESUMO
OBJECTIVE: To investigate the prevalence of blindness and moderate and severe visual impairment among adults aged 50 years or above in Ji'an county of Jiangxi province, China. METHODS: It was a population-based cross-section study. Geographically defined cluster sampling was used in 5402 randomly selected individuals aged ≥ 50 years in 28 clusters in Ji'an from September to November 2006. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. All participants were enumerated through village registers followed door-to-door visits. Eligible individuals were invited to receive visual acuity measurement and eye examination. Statistical analyses were performed using Stata/SE Statistical Software, release 9.0. Chi-square test was used to investigate the association of age, gender and education with presenting and best corrected visual acuity. RESULTS: Five thousands four hundreds and two individuals were enumerated and 5010 persons were examined, the response rate was 92.74%. Based on the criteria of World Health Organization visual impairment classification in 1973, 78 persons were diagnosed as blindness, 265 persons were diagnosed as moderate and severe visual impairment defined as best corrected visual acuity, the prevalence of blindness and moderate and severe visual impairment were 1.56% and 5.29% respectively. Ninety-four persons were diagnosed as blindness, 726 persons were diagnosed as moderate and severe visual impairment defined as presenting visual acuity, the prevalence of blindness and moderate and severe visual impairment defined as presenting visual acuity was 1.88% and 14.50% respectively. The prevalence of blindness and moderate and severe visual impairment was higher in aged (trend χ(2) = 970.15, P = 0.000), female (χ(2) = 89.81, P = 0.000), and illiterate persons (trend χ(2) = 241.85, P = 0.000). Cataract was still the first leading cause of blindness and visual impairment, the retinal diseases was the second. Un-corrected refractive error also was the main cause of visual impairment. CONCLUSIONS: The prevalence of blindness and moderate and severe visual impairment was higher than other district in China. The first leading cause of blindness and visual impairment is still cataract.
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Cegueira/epidemiologia , Baixa Visão/epidemiologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Catarata/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Transtornos da Visão/epidemiologiaRESUMO
OBJECTIVE: To estimate the prevalence of cataract, the outcomes of cataract surgery, cataract surgical coverage rate, cataract blindness social burden rate in Ji'an county of Jiangxi province, China. METHODS: Cluster sampling was used in randomly selected 5010 individuals aged ≥ 50 years in Ji'an county of Jiangxi province. All individuals were received visual acuity and eye examination, including the evaluation of lens status and cataract surgical status by slit lamp biomicroscopy. Data bank was established by Epi-info Software. Statistical analyses were performed using Stata/SE Statistical Software, release 9.0 (Stata Corp, College Station, TX). Confidence intervals and P values (considered significance at the P < 0.05 level) for prevalence of cataract, cataract surgical coverage rate, cataract blindness social burden rate and outcomes of surgery were calculated with adjustment for clustering effects and stratification associated with the sampling design. RESULTS: In 5010 individuals, 1158 cases of cataract were found, the prevalence of cataract was 23.11% among adults aged 50 or above. The prevalence of cataract was higher in the aged, female (P < 0.01). In 99 eyes with cataract surgery, 50.51% and 5.05% of eyes were performed by the modern extra-capsular surgery and phacoemulsification respectively. The rate of intraocular lens implantation was 55.56%. Post-operative presenting and best corrected visual acuity equal to or more than 0.7 was 10.1% and 45.5% of operated eyes respectively. The main causes of the post-operated eyes with worse visual acuity were post-capsular opacity and refractive error. The cataract surgical coverage rate was 32.29%, and the cataract blindness social burden rate was 3.83%. The cataract surgical rate was lower and cataract blindness social burden rate was higher in the aged persons (P < 0.01). CONCLUSIONS: Cataract is the most common eye disease that may lead into blindness and severe visual impairment among older adults aged equal or more than 50 years. The cataract surgical coverage rate is not high but the cataract blindness social burden rate is heavy in Ji'an county. The rate of intraocular lens implantation need increase and the visual outcomes of the surgery should be further improved in the future.
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Cegueira/epidemiologia , Extração de Catarata/estatística & dados numéricos , Catarata/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
OBJECTIVE: To search for the characteristics of MFS in corneal morphology and thickness. METHODS: Twenty-four patients (48 eyes) with MFS and 24 healthy age- and gender-matched volunteers (48 eyes) were recruited in this clinical prospective, and comparative series study. Firstly, biomicroscopic examination and Type-A ultrasonometry was conducted to search for ectopia lentis and axis length. Secondly, the corneal morphologic parameter [including the height of anterior and posterior surface, the centre corneal curvature, the mean astigmatism in the 3.0-mm central zone (Mean A), the mean simulated astigmatism (Sim A), the mean keratometry in the 3.0-mm central zone (Mean K), the mean simulated keratometry (Sim K), the 3.0-mm zone irregularity (3.0ZI), the 5.0-mm zone irregularity (5.0ZI), corneal thickness index (CTI)] and thickness (at the central location and at eight midperipheral locations) were obtained by the the autorefractometer and the Orbscan II Z corneal topography. Last, the statistics method including Crosstabs, One-way ANOVA, student-t test and discriminant analysis were applied and the correlations were established. RESULTS: There is no statistically significance between MFS group and control group in ages (38 ± 7) and (37 ± 8) years, gender (8/16) and (9/15), and axis length (23.12 ± 1.06) mm and (24.26 ± 2.96) mm (age χ(2) = 0.091, P = 0.763;gender t = 0.324, axis length t = 1.976, P > 0.05). Flat cornea ratio (66.7% and 12.5%) and topography of the oval (25.0% and 16.7%), irregular bow-shaped (41.7% and 37.5%) and irregular-shaped (12.5% and 8.3%) were increased significantly in patients with MFS. The corneal topography (MFS/control) showed that there are statistically significance in the thinnest thickness of cornea (489.8 ± 42.9)µm and (544.8 ± 25.7)µm, Mean K (40.60 ± 1.30) D and (42.80 ± 1.40) D, Sim K (40.50 ± 1.30) D and (42.80 ± 1.20) D, Sim A (1.08 ± 0.86)D and (0.91 ± 0.46) D, CTI 1.57 ± 0.24 and 1.21 ± 0.14, 3.0ZI (1.76 ± 0.96) D and (1.54 ± 0.82) D, and 5.0ZI (1.91 ± 1.26) D and (0.92 ± 0.68) D (thinnest thickness t = 6.996, Mean K t = 2.554, Sim K t = 3.326, Sim A t = 2.324, CTI t = 3.116, 3.0ZI t = 2.686, 5.0ZI t = 3.768, P < 0.05), while no statistically significance in the Mean A between the MFS (1.11 ± 0.89) D and control group (0.99 ± 0.49) D (Mean A t = 1.898, P = 0.08); except for temple inferior, the significant decrease of pachymetry (including the center and the seven midperipheral locations) appeared in the MFS group compared with the control group. CONCLUSION: The characteristic of MFS in corneal topography is that corneal axial refractive power descends and corneal thickness decreases.
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Córnea/patologia , Síndrome de Marfan/patologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVE: To evaluate the visual development and prevalence of amblyopia, strabismus among preschool children. METHODS: A random sample survey was performed in 4 610 preschool children from both urban and rural, aged 3 to 6 years. Participants underwent eye examination including visual acuity, refractive status, eye position, strabismus and amblyopia. RESULTS: Percentage of visual acuity above 1.0 was 28.4%, 39.3%, 46.2% and 76.5% in children of 3, 4, 5 and 6-year-old group, respectively. The mean visual acuity of each group was 0.63 ± 0.19 in 3-years old, 0.69 ± 0.16 in 4-year-old, 0.71 ± 0.22 in 5-year-old, 0.79 ± 0.29 in 6-year-old. Rural children have better vision acuity compared with those from urban. Hypermetropic was frequent refractive errors. Manifeststrabismus was found in 2.21%, with exotropia being more prevalence than esotropia; detection rate of recessive strabismus was 33.52%, mainly being exophoria; Based on current diagnostic criteria, the prevalence of amblyopia were 2.93% in 6 year-old group, 4.81% in 5-year-old group, 16.21% in 4-year-old group, 33.33% in 3-year-old group. CONCLUSION: Vision acuity is increasing with age in preschool population. A diagnosis standard of amblyopia suitable for each age group should be established to substitute the current one which has a high visual standard for amblyopia. Refractive error, strabismus and amblyopia are the leading causes of visual impairment among preschool-aged children, which represent the focus of prevention of blindness in preschool children.
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Ambliopia/epidemiologia , Erros de Refração/epidemiologia , Estrabismo/epidemiologia , Baixa Visão/etiologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Acuidade VisualRESUMO
AIM: To compare the results of visual acuity (VA) measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart, 5 m Standard Logarithm Visual Acuity (5SL) chart, and 2.5 m Standard Logarithm Visual Acuity (2.5SL) chart in outpatients of age 12-80y. METHODS: Each patient (totally 2000 outpatients) had both eyes tested with ETDRS chart at 4 m, 5SL chart at 5 m, and 2.5SL chart at 2.5 m in random order. The VA values of outpatients were categorized by ages. VA values were expressed by logMAR recording method. RESULTS: The mean VA results of ETDRS charts, 5SL, and 2.5SL chart were 0.52±0.28, 0.50±0.30, and 0.46±0.28 logMAR, respectively. There was a statistically significant difference in the three eye charts in the whole group (P<0.001). For all subjects, the correlation of VA tested with three charts was statistically significant (Spearman correlation coefficient=0.944, 0.937, 0.946, all P<0.001). Bland-Altman analysis shows the 95% limits of agreement between the 5SL and 2.5SL chart were -0.182 to 0.210, -0.139 to 0.251, and -0.151 to 0.235 logMAR, respectively). CONCLUSION: The agreement between the three eye charts is not high. The VA measured by 5SL chart is slightly better than that by ETDRS chart and 5SL chart would be a suitable alternative when ETDRS chart are not available in the clinical situation. The VA measured by 2.5SL chart is about 0.5 line better than VA tested with ETDRS chart, which may overestimate VA.
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AIM: To explore the intrinsic brain activity variations in retinal vein occlusion (RVO) subjects by using the voxel-wise degree centrality (DC) technique. METHODS: Twenty-one subjects with RVO and twenty-one healthy controls (HCs) were enlisted and underwent the resting-state functional magnetic resonance imaging (rs-fMRI) examination. The spontaneous cerebrum activity variations were inspected using the DC technology. The receiver operating characteristic (ROC) curve was implemented to distinguish the DC values of RVOs from HCs. The relationships between DC signal of definite regions of interest and the clinical characteristics in RVO group were evaluated by Pearson's correlation analysis. RESULTS: RVOs showed notably higher DC signals in right superior parietal lobule, middle frontal gyrus and left precuneus, but decreased DC signals in left middle temporal gyrus and bilateral anterior cingulated (BAC) when comparing with HCs. The mean DC value of RVOs in the BAC were negatively correlated with the anxiety and depression scale. CONCLUSION: RVO is associated aberrant intrinsic brain activity patterns in several brain areas including pain-related as well as visual-related regions, which might assist to reveal the latent neural mechanisms.
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AIM: To investigate whether inhibition of acetylcholinesterase (AChE) by donepezil ameliorate aberrant retinal neovascularization (RNV) and abnormal glial activation in oxygen-induced retinopathy (OIR). METHODS: A mouse model of RNV was induced in postnatal day 7 (P7) mice by exposure to 75% oxygen. Donepezil was administrated to P12 mice by intraperitoneal injection. Expression and localization of AChE in mouse retinas were determined by immunofluorescence. RNV was evaluated by paraffin sectioning and hematoxylin and eosin (HE) staining. Activation of retinal Müller glial cells were examined by immunoblot of glial fibrillary acidic protein (GFAP). rMC-1, a retinal Müller cell line, was used for in vitro study. Expression of hypoxia-induced factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) were determined by Western-blot analysis, enzyme-linked immunosorbent assay (ELISA) or immunostaining. RESULTS: Aberrant RNV and glial activation was observed after OIR. Of note, retinal AChE was mainly expressed by retinal Müller glial cells and markedly increased in OIR mice. Systemic administration of donepezil significantly reduced RNV and abnormal glial activation in mice with OIR. Moreover, ischemia-induced HIF-1α accumulation and VEGF upregulation in OIR mouse retinas and cultured rMC-1 were significantly inhibited by donepezil intervention. CONCLUSION: AchE is implicated in RNV with OIR. Inhibition of AChE by donepeizl is likely to be a potential therapeutic approach for retinal neovascular diseases.
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The aim of the present study was to investigate the changes of retinal microvascular network in patients with central serous chorioretinopathy (CSCR). A total of fifteen patients (right eye) with CSCR and 15 normal controls (right eye) were recruited. We used optical coherence tomography angiography to scan 6x6 mm macular retinal blood flow images with the application of a series of customized image segmentation processing program software to obtain microvascular and macrovascular density, and compared the superficial microvascular (SMIR), superficial macrovascular ring (SMAR) and the superficial total microvascular (STMI) density between CSCR patients and control group. Using the annular partition (C1C6) and quadrant partition methods on the macular, we compared the retinal vessel density changes. We also performed ROC analysis of superficial retinal microvessel density in CSCR retina to investigate the relationship between the microvascular density, the foveal thickness and visual acuity. The density of STMI and SMIR decreased in macular area in the patients with CSCR compared to the normal controls (P<0.05), while the density of SMAR did not change significantly. We found no significant difference in the density of SMIR with the quadrant partition method, whereas the annular partition method showed significantly decreased SMIR density only in the C1 region in patients with CSCR (P<0.05), with no significant difference observed in C2C6 regions. The density of SMIR had the highest differentiation power in the CSCR group, whereas the density of SC1 ring had the lowest differentiation power by the annular method. The largest area under the ROC curves was 0.77. The correlation index of the SMIR density and visual acuity was 0.544, whereas macular thickness and visual acuity was 0.644 in the CSCR group. The density of STMI and SMIR were decreased in patients with CSCR, which might provide further understanding of the pathogenesis of CSCR.
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Coriorretinopatia Serosa Central/diagnóstico , Microvasos/patologia , Vasos Retinianos/patologia , Adulto , Coriorretinopatia Serosa Central/patologia , Feminino , Humanos , Macula Lutea/irrigação sanguínea , Macula Lutea/patologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Tomografia de Coerência Óptica , Acuidade VisualRESUMO
AIM: To compare the effectiveness of combined fenofibrate and spironolactone with fenofibrate alone for treatment of central serous chorioretinopathy (CSCR). METHODS: Totally 60 patients (60 eyes) with a history of acute CSCR were randomed into two groups: group A with combination of fenofibrate (200 mg) and spironolactone (100 mg), and group B with only fenofibrate (200 mg). They were taken half an hour before meals and once per day for 8wk. The changes of the visual acuity, subjective symptom, ocular surface disease index (OSDI), the tear film and optical coherence tomography were observed at 2, 4, 6, and 8wk before and after treatment. RESULTS: The best corrected visual acuity (BCVA, logMAR) was improved to 0.22 and 0.27 after treatment from baseline of 0.35 and 0.36 in groups A and B (P<0.05), respectively. After 8wk treatment, the central subfield thickness (CST), and subretinal fluid volumn (SFV) decreased significantly to 49.5% and 78.8% in group A and 37.0% and 57.2% in group B. There were significant differences of CST and SFV in both groups (all P<0.05). CONCLUSION: Fenofibrate combined with spironolactone may have more clinical efficacy in the treatment of CSCR than fenofibrate only.
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Chemical burns are a major cause of corneal injury. Oxidative stress, inflammatory responses and neovascularization after the chemical burn aggravate corneal damage, and lead to loss of vision. Although NADPH oxidases (Noxs) play a crucial role in the production of reactive oxygen species (ROS), the role of Noxs in chemical burn-induced corneal injury remains to be elucidated. In the present study, the transcription and expression of Noxs in corneas were examined by RT-qPCR, western blot analysis and immunofluorescence staining. It was found that alkali burns markedly upregulated the transcription and expression of Nox2 and Nox4 in human or mouse corneas. The inhibition of Noxs by diphenyleneiodonium (DPI) or apocynin (Apo) effectively attenuated alkali burn-induced ROS production and decreased 3-nitrotyrosine (3-NT) protein levels in the corneas. In addition, Noxs/CD11b doubleimmunofluorescence staining indicated that Nox2 and Nox4 were partially co-localized with CD11b. DPI or Apo prevented the infiltration of CD11b-positive inflammatory cells, and inhibited the transcription of inflammatory cytokines following alkali burn-induced corneal injury. In our mouse model of alkali burn-induced corneal injury, corneal neovascularization (CNV) occurred on day 3, and it affected 50% of the whole area of the cornea on day 7, and on day 14, CNV coverage of the cornea reached maximum levels. DPI or Apo effectively attenuated alkali burninduced CNV and decreased the mRNA levels of angiogenic factors, including vascular endothelial growth factor (VEGF), VEGF receptors and matrix metalloproteinases (MMPs). Taken together, our data indicate that Noxs play a role in alkali burn-induced corneal injury by regulating oxidative stress, inflammatory responses and CNV, and we thus suggest that Noxs are a potential therapeutic target in the future treatment of chemical-induced corneal injury.
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Queimaduras Químicas/enzimologia , Lesões da Córnea/enzimologia , Queimaduras Oculares/enzimologia , NADPH Oxidases/metabolismo , Acetofenonas/farmacologia , Álcalis , Animais , Queimaduras Químicas/complicações , Queimaduras Químicas/tratamento farmacológico , Queimaduras Químicas/patologia , Lesões da Córnea/complicações , Lesões da Córnea/tratamento farmacológico , Lesões da Córnea/patologia , Neovascularização da Córnea/complicações , Neovascularização da Córnea/tratamento farmacológico , Neovascularização da Córnea/enzimologia , Neovascularização da Córnea/patologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Queimaduras Oculares/complicações , Queimaduras Oculares/tratamento farmacológico , Queimaduras Oculares/patologia , Humanos , Inflamação/patologia , Camundongos Endogâmicos C57BL , Oniocompostos/farmacologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
AIM: To evaluate the therapeutic effect of Nodinhibit-1 on alkali-burn-induced corneal neovascularization (CNV) and inflammation. The nucleotide-binding oligomerzation domain 1 (NOD1) is a potent angiogenic gene. METHODS: The alkali-burned rat corneas (32 right eyes) were treated with eye drops containing Nodinhibit-1 or phosphate buffered solution (PBS, PH 7.4) only, four times per day. CNV and inflammation were monitored using slit lamp microscopy, and the area of CNV was measured by formula. Vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) was determined by Western blot analysis. The TUNEL assay was used to assess the corneal apoptosis cells. RESULTS: Alkali-burn-induced progressive CNV and inflammation in the cornea. After treatment for 7d and 14d, there were statistically significant differences in the CNV areas and inflammatory index on that between two group(P<0.05, respectively). Epithelial defect quantification showed a significant difference between the two groups at days 4 and 7 after the alkali burns (P<0.05). The apoptotic cells on days 1, 4, and 7 between the two groups showed significant differences at all time points (P<0.05, respectively). Compared to that in control group, the protein level of VEGF expression was significantly reduced whereas the PEDF expression was increase in the Nodinhibit-1 groups on day 14 (P<0.05, respectively). CONCLUSION: Topical application of 10.0 µg/mL Nodinhibit-1 may have potential effect for the alkali burn-induced CNV and inflammation. The effect of Nodinhibit-1 on CNV may be by regulation the equilibrium of VEGF and PEDF in the wounded cornea.
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AIM: To determine the effect of different concentrations of the acetylcholinesterase (AChE) inhibitors tacrine and donepezil on retinal protection in AChE(+/-) mice (AChE knockout mice) of various ages. METHODS: Cultured ARPE-19 cells were treated with hydrogen peroxide (H2O2) at concentrations of 0, 250, 500, 1000 and 2000 µmol/L and protein levels were measured using Western blot. Intraperitoneal injections of tacrine and donepezil (0.1 mg/mL, 0.2 mg/mL and 0.4 mg/mL) were respectively given to AChE(+/-) mice aged 2mo and 4mo and wild-type S129 mice for 7d; phosphate buffered saline (PBS) was administered to the control group. The mice were sacrificed after 30d by in vitro cardiac perfusion and retinal samples were taken. AChE-deficient mice were identified by polymerase chain reaction (PCR) analysis using specific genotyping protocols obtained from the Jackson Laboratory website. H&E staining, immunofluorescence and Western blot were performed to observe AChE protein expression changes in the retinal pigment epithelial (RPE) cell layer. RESULTS: Different concentrations of H2O2 induced AChE expression during RPE cell apoptosis. AChE(+/-) mice retina were thinner than those in wild-type mice (P<0.05); the retinal structure was still intact at 2mo but became thinner with increasing age (P<0.05); furthermore, AChE(+/-) mice developed more slowly than wild-type mice (P<0.05). Increased concentrations of tacrine and donepezil did not significantly improve the protection of the retina function and morphology (P>0.05). CONCLUSION: In vivo, tacrine and donepezil can inhibit the expression of AChE; the decrease of AChE expression in the retina is beneficial for the development of the retina.
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AIM: To investigate the acetylcholinesterase (AChE) expression involved in retina pigment epithelial (RPE) apoptosis induced by higher concentrations H2O2. METHODS: The human retinal pigment epithelium cell line ARPE-19 was from ATCC (Rockville, MD). Cultured ARPE-19 cells were treated with H2O2 at 0, 250, 500, 1 000, 2 000µmol/L and cell viability was measured with MTT assay. AChE expression and DNA fragments were analyzed by immunocytochemistry, TUNEL and PARP-1 Western blotting. RESULTS: Immunofluorescence detected AChE exist in the normal human retinal tissue. When H2O2 >500µmol/L, AChE expression showed an increase after 2h, and this concentration was selected for the present study. RPE cell was induced with 1 000µmol/L H2O2 for 2h, compared to the control group, cell activity decline detected by MTT, AChE and PARP-1 protein expression was significantly increased detected by Western blotting. AChE immunofluorescence staining was positive in RPE cell after H2O2 incubate 2h. In addition, pretreatment with 100µmol/L epigallocatechin gallate (EGCG), cell viability increased from 31.20%±3.90% to 70.23%±12.96%. CONCLUSION: AChE is weakly expressed in normal human RPE cells. Stimulation with H2O2 caused the stable increase of AChE expression in RPE cells, which may indicate that AChE may be an important role in AMD.
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AIM: To evaluate the efficacy and safety of a novel sutureless AMT (amniotic membrane transplantation) or CAT (conjunctivolimbal autograft transplantation) using fibrin glue for reconstructing corneoconjunctival surfaces for primary pterygium associated with cysts. METHODS: A prospective descriptive study was made of the period 1 January 2006-1 May 2009. Nine patients with primary pterygium associated with cysts underwent pterygium and cyst excision followed by sutureless AMT or CAT using fibrin glue. RESULTS: During a mean follow-up of 8.00±0.67 months, all eyes maintained a smooth and stable corneal epithelial surface without recurrent erosion or persistent epithelial defect. The limbal donor site showed the presence of mild depressions without the formation of pseudopterygium. All eyes have good tear secretion function, tear film stability and ocular motility. CONCLUSION: Sutureless transplantation using fibrin glue is safe and effective for restoring a stable corneoconjunctival epithelium in primary pterygium associated with cysts.
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AIM: To evaluate the therapeutic efficacy of intracameral amphotericin B (ICAMB) injection in the treatment of keratomycosis. METHODS: The study design was a prospective controlled clinical trial. A total of 60 eyes of 60 patients were divided into two groups, 30 in the ICAMB injection group (group A) and 30 in the control group-topical application amphotericin B (group B). Serial measurements of the size of the keratomycosis-namely, two maximum linear dimensions perpendicular to each other, and the area and perimeter was done at start of therapy and follow up on day 3, 7, and 21. Rate of healing of the keratomycosis were measured as percentage decrease from the baseline parameter at each subsequent follow up. The data were analyzed by the non-parametric Wilcoxon rank sum test. RESULTS: The mean time to disappearance of hypopyon was 9.6±9.2 (range:1-26) days in group A and 26.8±20.8 (range:14-62) days in group B (P=0.03). The median percentage decrease in the size of the keratomycosis was significantly greater than that in the cord serum group at day 21(P<0.05) when measured in terms of the area and perimeter. A greater number of patients showed complete re-epithelialization in group A (n=27) than in group B (n=14) (P<0.05). None of the patients reported any side effects or discomfort with either treatment. CONCLUSION: ICAMB injection leads to faster healing of the keratomycosis refractory to all medical management and reducing time to disapperence of hypopyon compared to topical application amphotericin B.
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OBJECTIVE: To evaluate the efficacy of semiconductor low level laser irradiation for the treatment of postoperative exposure of hydroxyapatite orbital implants. METHODS: 22 cases with postoperative exposure of hydroxyapatite orbital implants were divided into three groups according to the size of implants exposure. The exposure wound in the 3 groups was irradated with semiconductor low level laser 5 min per day for 5-15 days. The follow-up period ranged from 2 to 24 months. RESULTS: In the group with less then 3 mm of exposure, the wound healed in 1 week after 5-10 days irradiation; in the group with implant exposure of 4-7 mm, the would healed in 1-2 weeks after 10-15 days irradiation; in the group with implant exposure of 8-10 mm, the would healed in 2-3 weeks after 10-15 days irradiation. Compared with the treatments of drugs and/or surgical repair, which was used for another 20 cases of exposure of hydroxyapatite orbital implants, semiconductor low level laser increased healing rate obviously in the groups with implant exposure of 4-7 mm and 8-10 mm (P = 0.019, 0.018). CONCLUSION: Semiconductor low level laser has better effects than drugs and/or surgical repair for exposure of hydroxyapatite orbital implants.