Decision-making Impairments in Primary Angle-closure Glaucoma Patients.

BACKGROUND: Primary angle-closure glaucoma (PACG) is a common eye disease and a common cause of blindness. Inappropriate medical decisions severely affect the prognosis. This study investigated decision-making under risk in PACG patients. METHODS: Thirty patients with first acute attack of PACG before surgery and thirty healthy controls were included in the study. Decision-making under risk was evaluated with the game of dice task (GDT). The results of Eysenck Personality Questionnaire (EPQ) and GDT between PACG patients and healthy controls were compared. RESULTS: Risky decisions in PACG patients were more than those in healthy controls as measured by mean score of GDT (12.47 ± 5.72 vs. 4.33 ± 3.30, P< 0.001). Higher neuroticism score in EPQ was found in PACG patients compared to healthy controls (14.97 ± 3.93 vs. 9.90 ± 4.49, P< 0.001). Neuroticism scores in EPQ were associated with decision-making performance (r = 0.417, P = 0.001). CONCLUSIONS: Neuroticism positively correlated with risky decisions. Decision-making might be influenced by neuroticism. Future studies will show whether therapy compliance will be improved by emotional management and psychological intervention in PACG patients.

Protective Effect of Rutin Against H2O2-Induced Oxidative Stress and Apoptosis in Human Lens Epithelial Cells.

PURPOSE: The aim of this study was to evaluate the effect of rutin on oxidative stress and apoptosis induced by H2O2 in human lens epithelial (HLE) cells and the associated mechanisms involved. METHODS: Cell viability was assessed by 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay and cell apoptosis was determined by flow cytometry, TUNEL assay and DNA fragmentation assay after 24 h treatment of 100 µM H2O2 with or without rutin pretreatment at various concentrations. The level of reactive oxygen species (ROS) was examined using 2',7'-dichlorodihydrofluorescein diacetate by flow cytometry. The activity of superoxide dismutase (SOD) was measured by xanthinoxidase method and the contents of glutathione (GSH) and malondialdehyde (MDA) were quantified by enzyme-linked immunosorbent assay. The expression change of Bcl-2, Bax and caspase-3 at mRNA and protein levels were detected by real-time polymerized chain reaction (RT-PCR) and Western-blot analysis, respectively. Activation and translocation of nuclear factor-kappaB (NF-кB/p65) were examined by Western blot and immunocytochemistry. RESULTS: Rutin pretreatment protected HLE cells from H2O2-induced cell viability decrease and apoptosis. In addition, in the presence of rutin, H2O2-induced intracellular excessive ROS and MDA were attenuated, whereas intracellular SOD and GSH depletion were prevented. Moreover, rutin also inhibited the up-regulation of caspase-3 and Bax expression and rescued down-regulation of Bcl-2 expression. Lastly, rutin blocked the activation and translocation of NF-кB/p65 induced by H2O2. CONCLUSIONS: Our results demonstrated that rutin effectively protects HLE cells from H2O2-induced oxidative stress and apoptosis in a dose-dependent manner. The involved mechanisms may be related to the regulation of ROS production, the inhabitation of lipid peroxidation, the protection of intracellular antioxidant system and its modulation of Bcl-2/Bax family and NF-кB/p65 signaling pathway.

Novel FOXL2 mutations in two Chinese families with blepharophimosis-ptosis-epicanthus inversus syndrome.

BACKGROUND: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disease. Mutations in the forkhead box L2 (FOXL2) gene cause two types of BPES distinguished by the presence (type I) and absence (type II) of premature ovarian failure (POF). The purpose of this study was to identify possible mutations in FOXL2 in two Chinese families with BPES. METHODS: Two large autosomal dominant Chinese BPES families were enrolled in this study. Genomic DNA was obtained from the leukocytes in peripheral venous blood. Four overlapping sets of primers were used to amplify the entire coding region and nearby intron sequences of the FOXL2 gene for mutations detection using polymerase chain reaction (PCR) and sequencing analyses. The sequencing results were analyzed using DNAstar software. RESULTS: All patients of the two families demonstrated typical features of BPES type II, including small palpebral fissures, ptosis, telecanthus, and epicanthus inversus without female infertility (POF). A novel FOXL2 heterozygous indel mutation c.675_690delinsT, including a 16-bp deletion and a 1-bp(T) insertion (p.Ala226_Ala230del), which would result in deletion of 5 alanine residues of a poly-alanine (poly-Ala) tract in the protein, was identified in all affected members of family A. A novel heterozygous missense mutation (c.223C > T, p.Leu75Phe) was identified in family B. CONCLUSIONS: Two novel FOXL2 mutations were identified in Chinese families with BPES. Our results expand the spectrum of FOXL2 mutations and provide additional structure-function insights into the FOXL2 protein.

Apolipoprotein E gene ε4ε4 is associated with elevated risk of primary open angle glaucoma in Asians: a meta-analysis.

BACKGROUND: Epidemiological studies have evaluated the association between Apolipoprotein E (APOE) gene ε2/ε3/ε4 polymorphism and glaucoma susceptibility. However, the published data are still inconclusive. The aim of the present study is to evaluate the impact of APOE gene ε2/ε3/ε4 polymorphism on glaucoma risk by using meta-analysis. METHODS: A comprehensive literature search of PubMed, EMBASE, Cochrane, Elsevier Science Direct and CNKI databases was conducted to identify relevant articles, with the last report up to January 5, 2014. Pooled odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association by using the fixed or random effect model. RESULTS: Fifteen separate studies including 2,700 cases and 2,365 controls were included in the meta-analysis. We did not detect a significant association between APOE gene ε2/ε3/ε4 polymorphism and glaucoma in overall population (P > 0.0083). In Asians, we detected an association of the ε4ε4 genotype with elevated risk for glaucoma (OR = 5.22, 95% CI = 1.85-14.68, P = 0.002), mainly for primary open angle glaucoma (OR = 4.98, 95% CI = 1.75-14.20, P = 0.003). CONCLUSIONS: The meta-analysis suggests that APOE gene ε4ε4 may be associated with elevated risk for primary open angle glaucoma in Asians. However, more epidemiologic studies based on larger sample size, case-control design and stratified by ethnicity as well as types of glaucoma are suggested to further clarify the relationship between APOE gene ε2/ε3/ε4 polymorphism and genetic predisposition to glaucoma.

Mutations in the gene encoding the alpha-subunit of rod phosphodiesterase in consanguineous Pakistani families.

PURPOSE: To localize and identify the gene and mutations causing autosomal recessive retinitis pigmentosa (RP) in consanguineous Pakistani families. METHODS: Families were ascertained and patients underwent complete ophthalmological examinations. Blood samples were collected and DNA was extracted. A genome-wide scan was performed using 382 polymorphic microsatellite markers on genomic DNA from affected and unaffected family members, and lod scores were calculated. RESULTS: A genome-wide scan of 50 families gave a lod score of 7.4172 with D5S2015 using HOMOG1. RP in all 4 linked families mapped to a 13.85 cM (14.87 Mb) region on chromosome 5q31-33 flanked by D5S2090 and D5S422. This region harbors the PDE6A gene, which is known to cause autosomal recessive RP. Sequencing of PDE6A showed a homozygous single base pair change; c.889C->T, single base pair insertion; c.2218-2219insT, and single base pair substitution in the splice acceptor site; IVS10-2A->G in each of three families. In the fourth family linked to this region, no disease-causing mutation was identified in the PDE6A gene. CONCLUSIONS: These results provide strong evidence that mutations in PDE6A result in recessive RP in three consanguineous Pakistani families. Although a fourth family was linked to markers in the 5q31-33 interval, no mutation was identified in PDE6A.

Screening of the eight BBS genes in Tunisian families: no evidence of triallelism.

PURPOSE: To study Bardet-Biedl syndrome (BBS) in the Tunisian population and determine the presence of triallelism in the eight identified BBS genes. METHODS: DNA samples were collected from 19 consanguineous Tunisian families with BBS. Genome-wide scans were performed with microsatellite markers in 12 families, and two-point linkage analyses were performed. Direct sequencing was used to screen patients with BBS for mutations in all eight identified BBS genes. RESULTS: Mutations in the BBS genes were identified in nine families. In addition, a large consanguineous family (57004) showed linkage to the BBS7 locus, although no mutation was identified. Five novel mutations were present in the nine families: one in BBS2 (c.565C>T, p.ArgR189Stop), one in BBS5 (c.123delA, p.Gly42GlufsX11), one in BBS7 (g.47247455_47267458del20004insATA, p.Met284LysfsX7), and two in BBS8 (c.459+1G>A, p.Pro101LeufsX12 and c.355_356insGGTGGAAGGCCAGGCA, p.Thr124ArgfsX43). CONCLUSIONS: All families in which mutations were identified show changes in both copies of the mutant gene, and inheritance patterns in all families are consistent with autosomal recessive inheritance excluding any evidence of triallelism in the BBS genes in Tunisia.

Mutations in PIP5K3 are associated with François-Neetens mouchetée fleck corneal dystrophy.

François-Neetens fleck corneal dystrophy (CFD) is a rare, autosomal dominant corneal dystrophy characterized by numerous small white flecks scattered in all layers of the stroma. Linkage analysis localized CFD to a 24-cM (18-Mb) interval of chromosome 2q35 flanked by D2S2289 and D2S126 and containing PIP5K3. PIP5K3 is a member of the phosphoinositide 3-kinase family and regulates the sorting and traffic of peripheral endosomes that contain lysosomally directed fluid phase cargo, by controlling the morphogenesis and function of multivesicular bodies. Sequencing analysis disclosed missense, frameshift, and/or protein-truncating mutations in 8 of 10 families with CFD that were studied, including 2256delA, 2274delCT, 2709C-->T (R851X), 3120C-->T (Q988X), IVS19-1G-->C, 3246G-->T (E1030X), 3270C-->T (R1038X), and 3466A-->G (K1103R). The histological and clinical characteristics of patients with CFD are consistent with biochemical studies of PIP5K3 that indicate a role in endosomal sorting.