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1.
J Cell Mol Med ; 26(23): 5858-5871, 2022 12.
Article in English | MEDLINE | ID: mdl-36349481

ABSTRACT

As the main loading-bearing tissue of eye, sclera exerts an important role in the pathophysiology of glaucoma. Intraocular pressure (IOP) generates mechanical strain on sclera. Recent studies have demonstrated that sclera, especially the peripapillary sclera, undergoes complicated remodelling under the mechanical strain. However, the mechanisms of the hypertensive scleral remodelling in human eyes remained uncertain. In this study, peripapillary human scleral fibroblasts (ppHSFs) were applied cyclic mechanical strain by Flexcell-5000™ tension system. We found that CXC- ligands and CXCR2 were differentially expressed after strain. Increased cell proliferation and inhibited cell motility were observed when CXCR2 was upregulated under the strain, whereas cell proliferation and motility did not have a significant change when CXCR2 was knocked down. CXCR2 could facilitate cell proliferation ability, modulate the mRNA and protein expressions of type I collagen and matrix metalloproteinase 2 via JAK1/2-STAT3 signalling pathway. In addition, CXCR2 might inhibit cell migration via FAK/MLC2 pathway. Taken together, CXCR2 regulated protein production and affected cell behaviours of ppHSFs. It might be a potential therapeutic target for the hypertensive scleral remodelling.


Subject(s)
Fibroblasts , Glaucoma , Receptors, Interleukin-8B , Sclera , Humans , Extracellular Matrix , Fibroblasts/metabolism , Glaucoma/metabolism , Matrix Metalloproteinase 2/metabolism , Sclera/cytology , Receptors, Interleukin-8B/genetics , Receptors, Interleukin-8B/metabolism , Cell Movement , Stress, Mechanical , Cells, Cultured
2.
Front Physiol ; 12: 712509, 2021.
Article in English | MEDLINE | ID: mdl-34658907

ABSTRACT

Scleral extracellular matrix (ECM) remodeling is thought to play a critical role in the pathogenesis of glaucoma. Mechanical strain induced by elevated intraocular pressure can promote myofibroblast differentiation of fibroblasts and result in scleral ECM remodeling; however, the underlying mechanism remains poorly understood. Yes-associated protein (YAP) is a mechanosensory protein and the key downstream transcriptional effector of the Hippo signaling pathway. Here, we investigated the role of YAP in mechanical strain-induced myofibroblast transformation during glaucoma scleral ECM remodeling. Integrative bioinformatics analyses were performed to identify the key pathways for the ECM remodeling of the sclera in glaucoma. Sprague-Dawley rats were used to establish a chronic ocular hypertension model, and the expression of collagen type I (COL1) and YAP in the sclera was analyzed by immunohistochemical analysis and Western blotting. Furthermore, human scleral fibroblasts (HSFs) were cultured and subjected to mechanical strain. In groups with or without the YAP siRNA or YAP inhibitor, cell proliferation, migration capacity, and the expression levels of YAP, COL1, and α-smooth muscle actin (α-SMA) were evaluated by Cell Counting Kit-8 assay, scratch assay, and Western blotting. The interactions between YAP and Smad3 were demonstrated by coimmunoprecipitation, and the expression levels of COL1 and α-SMA were evaluated in groups treated with or without the Smad3 inhibitor. We first revealed that the Hippo signaling pathway may be involved in mechanical strain-induced scleral ECM remodeling through bioinformatics analysis. Furthermore, the in vivo study showed upregulated YAP, COL1, and α-SMA expression in the hypertensive sclera of rats. In vitro, mechanical strain increased YAP and COL1 expression in HSFs and promoted myofibroblast differentiation. After YAP knockdown or inhibition with verteporfin, mechanical strain-induced fibrotic changes in HSFs were markedly suppressed. Additionally, YAP showed a protein interaction with Smad3, and the upregulation of a-SMA and COL1 in response to mechanical strain was also significantly downregulated following the inhibition of Smad3. In conclusion, mechanical strain activated scleral myofibroblast differentiation via YAP. The YAP pathway may play an important role in regulating scleral myofibroblast differentiation and ECM remodeling of the sclera in glaucoma.

3.
Int J Med Sci ; 18(7): 1554-1565, 2021.
Article in English | MEDLINE | ID: mdl-33746571

ABSTRACT

Background: Glaucoma is a leading cause of irreversible blindness. Remodeling of the scleral extracellular matrix (ECM) plays an important role in the development of glaucoma. The aim of this study was to identify the key genes and pathways for the ECM remodeling of sclera in glaucoma by bioinformatics analysis and to explore potential therapeutic agents for glaucoma management. Methods: Genes associated with glaucoma, sclera and ECM remodeling were detected using the text mining tool pubmed2ensembl, and assigned Gene Ontology (GO) biological process terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using the GeneCodis program. A protein-protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape, module analysis was performed using the Molecular Complex Detection (MCODE) plugin, and GO and KEGG analyses of the gene modules were performed using the Database of Annotation, Visualization and Integrated Discovery (DAVID) platform. The genes that clustered in the significant module were selected as core genes, and functions and pathways of the core genes were visualized using ClueGO and CluePedia. Lastly, the drug-gene interaction database was used to explore drug-gene interactions of the core genes to find drug candidates for glaucoma. Results: We identified 125 genes common to "Glaucoma", "Sclera", and "ECM remodeling" by text mining. Gene functional enrichment analysis yielded 30 enriched GO terms and 20 associated KEGG pathways. A PPI network that included 60 nodes with 249 edges was constructed, and three gene modules were obtained using the MCODE. We selected 13 genes that clustered in module 1 as core candidate genes that were associated mainly with ECM degradation and cell proliferation and division. The HIF-1 signaling pathway, FOXO signaling pathway, PI3K-Akt signaling pathway and TGFB signaling pathway were found to be enriched. We found that 11 of the 13 selected genes could be targeted by 26 existing drugs. Conclusions: The results showed that VEGFA, TGFB1, TGFB2, TGFB3, IGF2, IGF1, EGF, FN1, KNG1, TIMP1, SERPINE1, THBS1, and VWF were potential key genes involved to scleral ECM remodeling. Furthermore, 26 drugs were identified as potential therapeutic agents for glaucoma treatment and management.


Subject(s)
Drug Discovery , Extracellular Matrix/pathology , Glaucoma/genetics , Sclera/pathology , Computational Biology , Datasets as Topic , Gene Expression Profiling , Gene Regulatory Networks/drug effects , Glaucoma/drug therapy , Glaucoma/pathology , Humans , Molecular Targeted Therapy/methods , Protein Interaction Mapping , Protein Interaction Maps/drug effects , Sclera/cytology , Signal Transduction/drug effects , Signal Transduction/genetics
4.
Int J Ophthalmol ; 14(1): 112-119, 2021.
Article in English | MEDLINE | ID: mdl-33469492

ABSTRACT

AIM: To evaluate the driving performance in young and middle-aged Chinese glaucoma patients with mild to severe visual field loss compared to those without glaucoma by using a driving simulation test. METHODS: Twenty-nine participants were included in this study: nine patients with glaucoma but pass the binocular Esterman visual field test, ten patients with glaucoma and fail the binocular Esterman visual field test, and ten age-matched healthy controls. A driving simulation test was designed as a frequency-based analysis of a lane-keeping task. The total performance error, the control-response amplitude and delay were calculated. RESULTS: Esterman visual field test fail group showed the longest delay of control-response among three groups (P=0.02). And the delay in lane-keeping task was significantly associated with inferior field of better-eye (r=0.51, P=0.004) and integrated visual field (r=0.55, P=0.002). CONCLUSION: Young and middle-aged glaucoma patients with binocular visual field loss suffered from a longer delay of response in driving simulation test, while inferior visual field having more impact than superior visual field.

5.
Front Physiol ; 11: 682, 2020.
Article in English | MEDLINE | ID: mdl-32719611

ABSTRACT

Intraocular pressure (IOP) generates stress and strains in the laminar cribrosa and sclera, which may affect the development and progression of glaucoma. Scleral stiffness and material components have changed under elevated IOP. However, the detailed changes of the components of the hypertensive sclera are not well understood. In this study, we aimed to investigate the changes of the main components in the scleral extracellular matrix (ECM), and matrix metalloproteinase 2 (MMP2) and their relationship with time under chronic elevated IOP in Sprague-Dawley rats. An ocular hypertension model was established in the right eyes by anterior chamber injection with 0.3% carbomer solution. The left eye was used as the contralateral control. Immunofluorescent imaging of the tissue frozen sections, Western blot analysis, and quantitative PCR (qPCR) were performed to detect the expressions of type I collagen (COL1), elastin, and MMP2 in the sclera. The ocular hypertension model was successfully established. As compared to the left eyes, the immunofluorescence imaging, Western blot analysis, and qPCR showed that COL1, elastin, and MMP2 were significantly increased in the right eyes at 1 week (all P < 0.05). At 2 weeks, COL1 in the right eyes tended to be lower than that in the left eyes, while elastin and MMP2 were still higher (all P < 0.05) in the right eyes. When the IOP was elevated for 4 weeks, both COL1 and MMP2 were lower than those in the left eyes (all P < 0.05), while elastin between the two eyes was similar (P > 0.05). Under this 4-week hypertensive state, COL1 and elastin were initially elevated at 1 week, and then obviously reduced from 2 to 4 weeks. Consistently, MMP2 was gradually increased, with a peak at 2 weeks, and then decreased at 4 weeks. In conclusion, the chronic elevated IOP induced dynamic scleral ECM alterations in rats in a pressure- and time-dependent manner. MMP2 may play an important role in the balance between ECM synthesis and degradation and could potentially be a novel target for glaucoma intervention.

6.
Front Genet ; 9: 488, 2018.
Article in English | MEDLINE | ID: mdl-30405695

ABSTRACT

To investigate the association of known candidate genes with the visual field (VF) progression of primary open angle glaucoma (POAG) in a Han Chinese population. We included 440 POAG patients in this study. Fourteen previously reported single nucleotide polymorphisms (SNPs) at five different gene regions (TGFBR3-CDC7, TMCO1, CDKN2B-AS1, ATOH7, and SIX1/SIX6) were genotyped. Age at diagnosis, gender, intraocular pressure (IOP), mean defect (MD) of VF, vertical cup disk ratio (VCDR), best corrected visual acuity (BCVA), central corneal thickness (CCT), and axial length (AL) were recorded at baseline. Patients were followed up for 5 years to evaluate VF progression over time. Clinical information and allele frequencies of 14 SNPs were compared between patients who progressed and who did not within 5 years by multivariate logistic regression. Survival analysis was performed to evaluate the contribution of the associated SNP by cox regression. Greater MD (P < 0.0001), increased VCDR (P = 0.0001), higher IOP (P = 0.0003), worse BCVA (P = 0.002), and older age (P = 0.030) at the baseline were associated with VF progression. Both multivariate logistic regression and cox regression survival analysis showed none of the 14 SNPs statistically associated with VF progression adjusted with age at diagnosis, gender, baseline MD, follow-up IOP, CCT, and AL. There were lack of association of SNPs at TGFBR3-CDC7, TMCO1, ATOH7, CDKN2B-AS1, SIX1/SIX6 loci with VF progression in POAG patients in Han Chinese. Further studies are needed to evaluate the association of genetic variants with VF progression.

7.
Invest Ophthalmol Vis Sci ; 59(6): 2401-2410, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29847646

ABSTRACT

Purpose: The purpose of this study was to explore the effect of mechanical strain on human scleral fibroblasts (HSFs) and compare cell behaviors of HSFs from distinct regions. Methods: Primary HSFs were cultivated using a digestive protocol. Cells were seeded on collagen I-coated Bioflex plates, and a FX-5000 tension system was used to perform biaxial mechanical strain in vitro. We applied 10%, 0.5-Hz mechanical strain. Cell behaviors of peripapillary and periphery HSFs were compared after the strain. Edu imaging, Cell Counting Kit-8 assay, and cell cycle flow cytometry were conducted to analyze cell proliferation ability. For cell apoptosis, flow cytometry of Annexin V/propidium iodide, caspase 3 activity, and Western blot were performed. Immunofluorescence, real-time PCR, and Western blot were used to investigate cell differentiation. A migration assay was also performed. Results: Under the mechanical strain of 10%, 0.5 Hz for 24 hours, the proliferation ability and cell apoptosis of peripapillary HSFs did not have a significant change. The expression of alpha-smooth muscle actin (α-SMA) slightly decreased. However, increased cell proliferation, attenuated cell apoptosis and more expression of α-SMA were shown in the periphery HSFs under the same condition. The migration rate was also increased for periphery HSFs, whereas it kept almost the same for peripapillary HSFs under 10%, 0.5-Hz strain for 8 hours. Conclusions: Mechanical strain affected the cell behaviors of HSFs. The different performance of cells from distinct regions may suggest familial linages of HSFs, probably induced by mechanical strain.


Subject(s)
Fibroblasts/pathology , Glaucoma/pathology , Sclera/pathology , Stress, Mechanical , Apoptosis , Cell Cycle , Cell Differentiation , Cell Division , Cell Proliferation , Cells, Cultured , Flow Cytometry , Glaucoma/metabolism , Glaucoma/physiopathology , Humans , Immunohistochemistry
8.
Sensors (Basel) ; 17(1)2017 Jan 19.
Article in English | MEDLINE | ID: mdl-28106820

ABSTRACT

Diabetes has become a leading cause of death worldwide. Although there is no cure for diabetes, blood glucose monitoring combined with appropriate medication can enhance treatment efficiency, alleviate the symptoms, as well as diminish the complications. For point-of-care purposes, continuous glucose monitoring (CGM) devices are considered to be the best candidates for diabetes therapy. This review focuses on current growth areas of CGM technologies, specifically focusing on subcutaneous implantable electrochemical glucose sensors. The superiority of CGM systems is introduced firstly, and then the strategies for fabrication of minimally-invasive and non-invasive CGM biosensors are discussed, respectively. Finally, we briefly outline the current status and future perspective for CGM systems.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus , Humans , Monitoring, Physiologic , Point-of-Care Systems
9.
Polymers (Basel) ; 9(4)2017 Mar 28.
Article in English | MEDLINE | ID: mdl-30970805

ABSTRACT

Patients of diabetes mellitus urgently need noninvasive and continuous glucose monitoring in daily point-of-care. As the tear glucose concentration has a positive correlation with that in blood, the hydrogel colloidal crystal integrated into contact lens possesses promising potential for noninvasive monitoring of glucose in tears. This paper presents a new glucose-responsive sensor, which consists a crystalline colloidal array (CCA) embedded in hydrogel matrix, attached onto a rigid gas permeable (RGP) contact lens. This novel sensing lens is able to selectively diffract visible light, whose wavelength shifts between 567 and 468 nm according to the alternation of the glucose concentration between 0 and 50 mM and its visible color change between reddish yellow, green, and blue. The detection limit of responsive glucose concentration can be reduced to 0.05 mM. Its combination with a contact lens endows it with excellent biocompatibility and portability, which shows great possibility for it to push the development of glucose-detecting devices into new era.

10.
PLoS One ; 10(7): e0133189, 2015.
Article in English | MEDLINE | ID: mdl-26214313

ABSTRACT

PURPOSE: To identify whether myopia was associated with the visual field (VF) progression of primary open-angle glaucoma (POAG). METHODS: A total of 270 eyes of 270 POAG followed up for more than 3 years with ≥9 reliable VFs by Octopus perimetry were retrospectively reviewed. Myopia was divided into: mild myopia (-2.99 diopter [D], 0), moderate myopia (-5.99, 3.00 D), marked myopia (-9.00, -6.00 D) and non-myopia (0 D or more). An annual change in the mean defect (MD) slope >0.22 dB/y and 0.30 dB/y was defined as fast progression, respectively. Logistic regression was performed to determine prognostic factors for VF progression. RESULTS: For the cutoff threshold at 0.22 dB/y, logistic regression showed that vertical cup-to-disk ratio (VCDR; p = 0.004) and the extent of myopia (p = 0.002) were statistically significant. When logistic regression was repeated after excluding the extent of myopia, axial length (AL; p = 0.008, odds ratio [OR] = 0.796) reached significance, as did VCDR (p = 0.001). Compared to eyes with AL≤23 mm, the OR values were 0.334 (p = 0.059), 0.309 (p = 0.044), 0.266 (p = 0.019), 0.260 (p = 0.018), respectively, for 23 26 mm. The significance of vertical cup-to-disk ratio of (p = 0.004) and the extent of myopia (p = 0.008) did not change for the cutoff threshold at 0.30dB/y. CONCLUSIONS: VCDR and myopia were associated with VF prognosis of POAG. Axial myopia may be a protective factor against VF progression.


Subject(s)
Glaucoma, Open-Angle , Myopia , Visual Fields , Adult , Female , Glaucoma, Open-Angle/diagnosis , Glaucoma, Open-Angle/pathology , Glaucoma, Open-Angle/physiopathology , Humans , Male , Middle Aged , Myopia/diagnosis , Myopia/pathology , Myopia/physiopathology , Prognosis
11.
Invest Ophthalmol Vis Sci ; 56(4): 2595-600, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25711633

ABSTRACT

PURPOSE: We investigated the association of genetic factors with primary open angle glaucoma (POAG), including high tension glaucoma (HTG) and normal tension glaucoma (NTG), in a Han Chinese population. METHODS: We recruited 1157 POAG cases, including 860 HTG and 297 NTG, and 934 normal controls. A total of 13 previously reported single nucleotide polymorphisms (SNPs) located at four gene regions (TMCO1, CDKN2B-AS1, ATOH7, and SIX1/SIX6) was genotyped. Distributions of allele frequencies were compared between cases and controls as well as in the HTG and NTG subgroups. The IOP, vertical cup-to-disc ratio (VCDR), central corneal thickness (CCT), axial length (AL), and age at diagnosis also were investigated as quantitative phenotypes with genotypes of these SNPs. RESULTS: The SNPs rs4656461 and rs7555523 at TMCO1, rs523096 and rs2157719 at CDKN2B-AS1, as well as rs33912345 and rs10483727 at SIX1/SIX6 showed statistically significant association with POAG. The SNPs at ATOH7 did not show statistically significant association with POAG in our dataset. In the subgroup analysis of HTG and NTG, multiple variants at CDKN2B-AS1 and SIX1/SIX6 showed stronger association with NTG than HTG. The SNPs rs523096 and rs2157719 at CDKN2B-AS1 as well as rs33912345 and rs10483727 at SIX1/SIX6 were found to be associated with IOP where the minor alleles were associated with an increase in IOP. In contrast, SNPs at TMCO1 showed significant association with HTG only. CONCLUSIONS: Genetic variants in CDKN2B-AS1, SIX1/SIX6, and TMCO1 were associated with POAG in a Han Chinese population. Genes CDKN2B-AS1 and SIX1/SIX6 seem to harbor a tendency toward POAG with lower IOP, while carriers of risk alleles at TMCO1 seem to be predisposed to developing POAG with higher IOP.


Subject(s)
DNA/genetics , Genetic Predisposition to Disease , Glaucoma, Open-Angle/genetics , Intraocular Pressure , Low Tension Glaucoma/genetics , Polymorphism, Genetic , China/epidemiology , Female , Gene Frequency , Genetic Variation , Genotype , Glaucoma, Open-Angle/epidemiology , Glaucoma, Open-Angle/physiopathology , Humans , Low Tension Glaucoma/epidemiology , Low Tension Glaucoma/physiopathology , Male , Middle Aged , Phenotype , Prevalence , Risk Factors
12.
J Glaucoma ; 24(9): 647-55, 2015 Dec.
Article in English | MEDLINE | ID: mdl-24844542

ABSTRACT

PURPOSE: To evaluate changes of anterior chamber angle (ACA) by anterior-segment optical coherence tomography (AS-OCT) in patients with primary angle closure glaucoma (PACG) following phacoemulsification (phaco) with or without goniosynechialysis (GSL). METHODS: Patients with PACG recruited into 2 randomized controlled trials comparing phaco-GSL versus phaco were pooled for analysis. Images of ACA were obtained by AS-OCT before surgery, and at 1 and 2 weeks, and 1, 3, and 6 months after surgery. The following parameters were analyzed: angle opening distance (AOD) at 500 and 750 µm from the scleral spur, trabecular-iris space area (TISA) at 500 and 750 µm, angle recess area (ARA) at 500 and 750 µm, and scleral spur angle (SSA). RESULTS: All parameters of ACA increased significantly after phaco-GSL (P<0.001), whereas no increase occurred in the phaco group. Negatively significant correlations were found in ΔAOD500 (P<0.05), ΔARA750 (P<0.05), ΔTISA500 (P<0.05), and ΔTISA750 (P<0.05) at 1, 3, and 6 months, and ΔSSA (P<0.05) at 3 and 6 months after phaco-GSL against Δ intraocular pressure (IOP). In the phaco-GSL group, 23 of 23 eyes had IOP<21 mm Hg without any antiglaucoma medication postoperatively. In the phaco group, 12 of 20 eyes (60%) had IOP<21 mm Hg without medication, 8 of 20 eyes required medication with IOP<21 mm Hg (15%) and uncontrollable IOP (25%) after surgery. CONCLUSIONS: On AS-OCT evaluation, ACA in eyes with PACG opened and widened significantly after phaco-GSL in our study. It is suggested that ΔAOD500, ΔARA750, ΔTISA500, ΔTISA750, and ΔSSA would provide valuable information to estimate the effectiveness of phaco-GSL.


Subject(s)
Anterior Chamber/pathology , Glaucoma, Angle-Closure/surgery , Iris/surgery , Phacoemulsification , Trabecular Meshwork/surgery , Aged , Aged, 80 and over , Female , Glaucoma, Angle-Closure/physiopathology , Gonioscopy , Humans , Intraocular Pressure/physiology , Iris/pathology , Lens Implantation, Intraocular , Male , Middle Aged , Prospective Studies , Tissue Adhesions/surgery , Tomography, Optical Coherence/methods , Tonometry, Ocular , Trabecular Meshwork/pathology
13.
Nat Genet ; 46(10): 1115-9, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25173107

ABSTRACT

We performed a genome-wide association study for primary open-angle glaucoma (POAG) in 1,007 cases with high-pressure glaucoma (HPG) and 1,009 controls from southern China. We observed genome-wide significant association at multiple SNPs near ABCA1 at 9q31.1 (rs2487032; P = 1.66 × 10(-8)) and suggestive evidence of association in PMM2 at 16p13.2 (rs3785176; P = 3.18 × 10(-6)). We replicated these findings in a set of 525 HPG cases and 912 controls from Singapore and a further set of 1,374 POAG cases and 4,053 controls from China. We observed genome-wide significant association with more than one SNP at the two loci (P = 2.79 × 10(-19) for rs2487032 representing ABCA1 and P = 5.77 × 10(-10) for rs3785176 representing PMM2). Both ABCA1 and PMM2 are expressed in the trabecular meshwork, optic nerve and other ocular tissues. In addition, ABCA1 is highly expressed in the ganglion cell layer of the retina, a finding consistent with it having a role in the development of glaucoma.


Subject(s)
ATP Binding Cassette Transporter 1/genetics , Genetic Predisposition to Disease/genetics , Glaucoma, Open-Angle/genetics , Phosphotransferases (Phosphomutases)/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Aged , Aged, 80 and over , Asian People/genetics , China , Chromosomes, Human, Pair 16/genetics , Chromosomes, Human, Pair 9/genetics , Female , Gene Expression , Genetic Predisposition to Disease/ethnology , Genome-Wide Association Study , Genotype , Glaucoma, Open-Angle/ethnology , Humans , Linkage Disequilibrium , Male , Middle Aged , Principal Component Analysis , Reverse Transcriptase Polymerase Chain Reaction , Singapore , Young Adult
14.
Invest Ophthalmol Vis Sci ; 55(6): 3797-802, 2014 May 22.
Article in English | MEDLINE | ID: mdl-24854855

ABSTRACT

PURPOSE: To investigate the association of PLEKHA7 and COL11A1 with primary angle closure glaucoma, as well as acute and chronic subphenotype, in a Han Chinese population. METHODS: A total of 984 cases, including 606 primary angle closure glaucoma (PACG) and 378 primary angle closure (PAC), and 922 normal controls were recruited. Twelve single nucleotide polymorphisms (SNPs) (rs1676486, rs3753841, rs12138977, rs2126642, rs2622848, rs216489, rs1027617, rs366590, rs11024060, rs6486330, rs11024097, and rs11024102) in the PLEKHA7 gene and COL11A12 gene were genotyped. Distributions of allele frequencies were compared between cases and controls as well as in patient subgroups with or without acute attacks. RESULTS: Four of the 12 SNPs, including rs1676486 (P = 0.0060) and rs12138977 (P = 0.028) in COL11A1, as well as rs216489 (P = 0.0074) and rs11024102 (P = 0.038) in PLEKHA7, were found to have a statistically significant association with PAC/PACG. In the subgroup analysis, 6 out of 12 SNPs (rs1676486, rs3753841, rs12138977, rs216489, rs11024060, and rs11024102) showed statistically significant differences between acute PAC/PACG cases and controls. However, none of them showed statistically significant differences between chronic PAC/PACG cases and controls. CONCLUSIONS: Our study suggests that rs1676486 and rs12138977 in COL11A1 as well as rs216489 and rs11024102 in PLEKHA7 are associated with an increased risk of PAC/PACG in the Han Chinese population, supporting prior reports of the association of COL11A1 and PLEKH7 with angle closure glaucoma. Both COL11A1 and PLEKHA7 were shown to confer significant risk for acute PAC/PACG. Further work is necessary to confirm the importance of COL11A1 and PLEKHA7 in the pathogenesis of glaucoma.


Subject(s)
Carrier Proteins/genetics , Collagen Type XI/genetics , DNA/genetics , Genetic Predisposition to Disease , Glaucoma, Angle-Closure/genetics , Polymorphism, Genetic , Carrier Proteins/metabolism , China/epidemiology , Collagen Type XI/metabolism , Female , Follow-Up Studies , Gene Frequency , Genetic Association Studies , Genotype , Glaucoma, Angle-Closure/epidemiology , Glaucoma, Angle-Closure/metabolism , Humans , Male , Middle Aged , Prevalence
15.
Qual Life Res ; 23(3): 999-1008, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24062238

ABSTRACT

PURPOSE: To assess vision-related quality of life (VRQoL) in Chinese glaucoma patients and explore its sociodemographic, clinical and psychological correlates, and determine which of them explain the largest variation. METHODS: This cross-sectional study included 508 Chinese glaucoma patients. Chinese-version Glaucoma Quality of Life-15 questionnaire (CHI-GQL-15) and Hospital Anxiety and Depression Scales were administered to all participants to evaluate their VRQoL and psychological distresses. Visual functions (habitual-corrected visual acuity (HCVA), intraocular pressure, and mean defect (MD) of visual field) were assessed through clinical examinations by professionals. Sociodemographic information and other treatment histories were collected via interviews and chart review. Stepwise multiple linear regression analyses were performed to identify sociodemographic, clinical, and psychological predictors of VRQoL. RESULTS: The mean summary score for CHI-GQL-15 was 28.79 ± 12.74. Patients exhibited the greatest difficulty in activities involving glare and dark adaptation (28.19 ± 22.86), followed by central and near vision (26.18 ± 26.56), peripheral vision (18.03 ± 21.37), and the least difficulty for outdoor mobility (15.06 ± 24.57). Moderate and heavy economic burden, HCVA and MD of both the better and the worse eyes, number of glaucoma surgeries in the treatment history and the presence of depression were independent predictors for VRQoL of glaucoma patients. Clinical factors explained the largest variation. CONCLUSION: VRQoL of glaucoma patients is multifactorial and was primarily determined by clinical indices. VRQoL assessment could be informative when adopted as a complement to objective visual measures in clinical practice.


Subject(s)
Glaucoma/psychology , Quality of Life , Adolescent , Adult , Aged , Aged, 80 and over , Anxiety Disorders/diagnosis , Anxiety Disorders/epidemiology , China/epidemiology , Comorbidity , Cross-Sectional Studies , Depressive Disorder/diagnosis , Depressive Disorder/epidemiology , Factor Analysis, Statistical , Female , Glaucoma/epidemiology , Humans , Male , Middle Aged , Multivariate Analysis , Psychiatric Status Rating Scales , Self Report , Socioeconomic Factors , Surveys and Questionnaires , Visual Acuity , Visual Fields , Young Adult
16.
Health Qual Life Outcomes ; 11: 188, 2013 Nov 05.
Article in English | MEDLINE | ID: mdl-24188457

ABSTRACT

BACKGROUND: Maintaining glaucoma patients' quality of life (QoL) has become one of the most important goals for treatments. The purpose of this study is to develop a Chinese version of Glaucoma Quality of Life-15 item Questionnaire (GQL-15-CHI), and examine its psychometric properties. METHODS: The Glaucoma Quality of Life-15 item Questionnaire (GQL-15) was translated and culturally adapted into Chinese, and administered to glaucoma patients recruited from Shanghai Eye and ENT Hospital. Visual functions: habitual-corrected visual acuity (HCVA), intraocular pressure (IOP), and mean defect (MD) of visual field) were assessed through clinical examination by professionals. Sociodemographic and other clinical data were collected via interviews and chart review. According to Nelson's glaucoma staging system, patients were stratified as mild, moderate, and severe visual field loss (VFL). The psychometric properties, including internal consistency, test-retest reliability, item-scale correlations and factor analysis were conducted. The divergent validity was assessed through bilateral comparisons of the GQL-15-CHI composite and subscale scores between patients of different VFLs after controlling for potential confounders. RESULTS: A total of 508 glaucoma patients were recruited (male: 265, female: 243). The mean age was 55.41 years. The Cronbach's α coefficients ranged from 0.75 to 0.91 for the subscales. The test-retest reliability, as estimated by the intraclass correlation coefficients, were above 0.70 for all subscales. Statistically significant differences were showed in the GQL-15-CHI summary and subscale scores after controlling for sociodemographic and clinical confounders (P < 0.05) among patients with different VFLs. CONCLUSION: The GQL-15-CHI showed psychometric properties comparable to those of the original English version, and thus could be used as a reliable and valid tool for assessment of QoL in Chinese glaucoma patients.


Subject(s)
Glaucoma/psychology , Language , Quality of Life/psychology , Surveys and Questionnaires/standards , Adolescent , Adult , Aged , China , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Psychometrics , Reproducibility of Results , Young Adult
17.
J Psychosom Res ; 75(1): 75-82, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23751243

ABSTRACT

OBJECTIVES: To assess the prevalence of anxiety and depression in Chinese glaucoma patients, and explore their predictive factors. METHODS: This cross-sectional study included 506 Chinese glaucoma patients. Hospital Anxiety and Depression Scales (HADS) and the Chinese-version Glaucoma Quality of Life-15 questionnaire (CHI-GQL-15) were administered to all participants to evaluate their psychological distresses and quality of life (QoL). Visual functions (habitual-corrected visual acuity (HCVA), intraocular pressure (IOP), and mean defect (MD) of visual field) were assessed through clinical examinations by professionals. Sociodemographic information and other treatment histories were collected via interviews and chart review. Multiple linear regression analyses were performed to identify predictors of anxiety and depression. To evaluate the impact of anxiety or depression on patients QoL, the CHI-GQL-15 summary and subscores of patients with and without psychological disturbances were compared using covariate-adjusted regression analyses. RESULTS: The prevalence of anxiety and depression in Chinese glaucoma patients was 22.92% and 16.40%, respectively. A younger age (ß=-0.058, p<0.001), female gender (ß=1.219, p=0.001), moderate and heavy economic burden (ß=1.186, p=0.009; ß=2.705, p<0.001, respectively) and the CHI-GQL-15 summary score (ß=0.101, p<0.001) were independent predictors of anxiety. Significant independent predictors of depression included the duration of glaucoma (ß=-0.065, p=0.019) and the CHI-GQL-15 summary score (ß=0.147, p<0.001). Difference in the CHI-GQL-15 summary and its subscores of patients with and without psychological disturbance were statistically significant (p<0.001). CONCLUSIONS: Prevalence of anxiety and depression among Chinese glaucoma patients is relatively high. Self-reported measures were informative in evaluating patients' psychological disturbances, whereas objective measures of visual function were not.


Subject(s)
Anxiety/epidemiology , Depression/epidemiology , Glaucoma/epidemiology , Quality of Life/psychology , Adolescent , Adult , Aged , Aged, 80 and over , Anxiety/diagnosis , Anxiety/psychology , Asian People , China/epidemiology , Comorbidity , Cross-Sectional Studies , Depression/diagnosis , Depression/psychology , Female , Glaucoma/psychology , Humans , Male , Middle Aged , Prevalence , Risk Factors , Self Report , Surveys and Questionnaires
18.
Ocul Immunol Inflamm ; 21(4): 286-91, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23718571

ABSTRACT

PURPOSE: To report the clinical features of Vogt-Koyanagi-Harada syndrome presented with bilateral acute angle closure glaucoma in 4 Chinese patients. METHODS: The medical records were retrospectively reviewed. RESULTS: Visual acuity ranged from counting fingers before the eye to 6/30. Intraocular pressure ranged from 22.2 to 29.7 mmHg with or without anterior chamber inflammation. Mild vitritis and massive exudative retinal detachment were seen. B scan and fundus fluorescein angiography supported the diagnosis. After corticosteroid treatment, the increased intraocular pressure was resolved with deepened anterior chamber and open angle. Inflammation was controlled and visual acuity was improved. CONCLUSIONS: Bilateral acute angle closure glaucoma could be the initial symptom of Vogt-Koyanagi-Harada syndrome. Mild increased intraocular pressure in association with moderate to severe visual disturbance in both eyes is an important sign of this diagnosis. Careful fundus examination and B scan are helpful in diagnosis.


Subject(s)
Glaucoma, Angle-Closure/etiology , Intraocular Pressure , Uveomeningoencephalitic Syndrome/complications , Acute Disease , Diagnosis, Differential , Female , Fluorescein Angiography , Follow-Up Studies , Fundus Oculi , Glaucoma, Angle-Closure/diagnosis , Glaucoma, Angle-Closure/physiopathology , Humans , Male , Microscopy, Acoustic , Middle Aged , Ophthalmoscopy , Retrospective Studies , Uveomeningoencephalitic Syndrome/diagnosis , Uveomeningoencephalitic Syndrome/physiopathology , Visual Acuity
19.
Clin Exp Ophthalmol ; 41(9): 881-90, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23566072

ABSTRACT

BACKGROUND: The interaction of copolymer-1-activated T cells and microglia on retinal ganglion cells survival in vitro was explored. METHODS: Copolymer-1-specific T cells were made by repeated copolymer-1 stimulation of T cells, microglia were isolated from the retinas of newborn rats, and then, they were co-cultured (the experimental group) for 48 h. Retinal ganglion cells were collected from the retinas of adult rats, purified, and then, the supernatants from different groups were added. After 72 h, terminal-deoxynucleotidyl transferase-mediated d-UTP nick end labelling analysis was used to observe retinal ganglion cell apoptosis, and reverse transcription polymerase chain reaction was used to test messenger RNA expression of Caspase-3 and Caspase-8. The levels of cytokines, including insulin-like growth factor-1, brain-derived neurotrophic factor, tumour necrosis factor-α and interleukin-10, in the supernatants were examined by enzyme-linked immunosorbent assay to explore the possible mechanisms undergoing. RESULTS: After 72 h, the mean retinal ganglion cell apoptosis rate in the experimental group was the lowest (25.36%) among the groups. The messenger RNA expression of Caspase-3 and Caspase-8 in this group was significantly lower than that of the control groups (both P < 0.05). The secretion of interlekin-10 and brain-derived neurotrophic factor, insulin-like growth factor-1 and tumour necrosis factor-α in the supernatant of the experimental group were higher than that of the control groups (both P < 0.05) after co-culture. CONCLUSIONS: The interaction of copolymer-1-specific T cells with microglia could reduce retinal ganglion cell apoptosis. The related immune mechanisms were complicated. Upregulation of brain-derived neurotrophic factor and insulin-like growth factor-1, and the balance of some pro-inflammatory and anti-inflammatory cytokines may be involved in this protective autoimmunity.


Subject(s)
Immunosuppressive Agents/pharmacology , Lymphocyte Activation/drug effects , Microglia/cytology , Peptides/pharmacology , Retinal Ganglion Cells/cytology , T-Lymphocytes/immunology , Animals , Apoptosis/immunology , Autoimmunity/physiology , Cell Communication/physiology , Cell Survival/physiology , Coculture Techniques , Cytokines/genetics , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Gene Expression , Glatiramer Acetate , In Situ Nick-End Labeling , Microscopy, Fluorescence , RNA, Messenger/genetics , Rats , Rats, Wistar , Real-Time Polymerase Chain Reaction , Retinal Ganglion Cells/metabolism
20.
Ophthalmologica ; 228(3): 167-73, 2012.
Article in English | MEDLINE | ID: mdl-22739037

ABSTRACT

AIMS: To compare the effectiveness of combined phacoemulsification and viscogoniosynechialysis versus trabeculectomy alone in primary angle-closure glaucoma (PACG) with a coexisting cataract. METHODS: Thirty-nine Chinese patients (39 eyes) were retrospectively analyzed: 19 patients underwent combined phacoemulsification and viscogoniosynechialysis (group 1), and 20 underwent trabeculectomy (group 2). In both groups, the intraocular pressure (IOP), the number of antiglaucoma medications, the best corrected visual acuity (BCVA), the central anterior chamber depth (ACD), the synechial/apposition angle closure (SAC), and the success rates were assessed. RESULTS: The median follow-up periods were similar for both groups (10 months). At the last follow-up, the mean IOP was 14.09 ± 6.89 mm Hg and the mean number of antiglaucoma medications was 0.36 ± 0.59 in group 1; in group 2, the mean IOP was 16.48 ± 4.74 mm Hg (p = 0.066) and the mean number of antiglaucoma medications was 1.05 ± 0.99 (p = 0.025). In terms of the mean central ACD and the mean SAC, there were significant differences between the groups (p = 0.0000, respectively). Kaplan-Meier analysis revealed that the cumulative probability of success in group 1 was higher than that in group 2 (p = 0.0051). CONCLUSION: Compared to trabeculectomy, combined phacoemulsification and viscogoniosynechialysis resulted in a lower requirement for glaucomatous medications, a greater improvement in BCVA, and a higher cumulative probability that treatment would be successful among patients with PACG and coexisting cataracts.


Subject(s)
Cataract/complications , Glaucoma, Angle-Closure/complications , Glaucoma, Angle-Closure/surgery , Phacoemulsification , Trabeculectomy , Viscosupplements/therapeutic use , Aged , Aged, 80 and over , Anterior Eye Segment/drug effects , Antihypertensive Agents/administration & dosage , Cataract/physiopathology , Female , Glaucoma, Angle-Closure/physiopathology , Gonioscopy , Humans , Intraocular Pressure/physiology , Male , Middle Aged , Retrospective Studies , Surgical Flaps , Tonometry, Ocular , Treatment Outcome , Visual Acuity/physiology
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