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1.
David W. Collins Harini V. Gudiseva Benjamin T. Trachtman Matthew Jerrehian Thomasine Gorry William T. Merritt III Allison L. Rhodes Prithvi S. Sankar Meredith Regina Eydie Miller-Ellis Joan M. O’Brien 《PloS one》2013,8(10)
Primary open-angle glaucoma (POAG) is a major cause of blindness and results from irreversible retinal ganglion cell damage and optic nerve degeneration. In the United States, POAG is most prevalent in African-Americans. Mitochondrial genetics and dysfunction have been implicated in POAG, and potentially pathogenic sequence variations, in particular novel transversional base substitutions, are reportedly common in mitochondrial genomes (mtDNA) from POAG patient blood. The purpose of this study was to ascertain the spectrum of sequence variation in mtDNA from African-American POAG patients and determine whether novel nonsynonymous, transversional or other potentially pathogenic sequence variations are observed more commonly in POAG cases than controls. mtDNA from African-American POAG cases (n = 22) and age-matched controls (n = 22) was analyzed by deep sequencing of a single 16,487 base pair PCR amplicon by Ion Torrent, and candidate novel variants were validated by Sanger sequencing. Sequence variants were classified and interpreted using the MITOMAP compendium of polymorphisms. 99.8% of the observed variations had been previously reported. The ratio of novel variants to POAG cases was 7-fold lower than a prior estimate. Novel mtDNA variants were present in 3 of 22 cases, novel nonsynonymous changes in 1 of 22 cases and novel transversions in 0 of 22 cases; these proportions are significantly lower (p<.0005, p<.0004, p<.0001) than estimated previously for POAG, and did not differ significantly from controls. Although it is possible that mitochondrial genetics play a role in African-Americans’ high susceptibility to POAG, it is unlikely that any mitochondrial respiratory dysfunction is due to an abnormally high incidence of novel mutations that can be detected in mtDNA from peripheral blood. 相似文献
2.
Carolina P. B. Gracitelli Andrew J. Tatham Erwin R. Boer Ricardo Y. Abe Alberto Diniz-Filho Peter N. Rosen Felipe A. Medeiros 《PloS one》2015,10(10)
Purpose
To evaluate the ability of longitudinal Useful Field of View (UFOV) and simulated driving measurements to predict future occurrence of motor vehicle collision (MVC) in drivers with glaucoma.Design
Prospective observational cohort study.Participants
117 drivers with glaucoma followed for an average of 2.1 ± 0.5 years.Methods
All subjects had standard automated perimetry (SAP), UFOV, driving simulator, and cognitive assessment obtained at baseline and every 6 months during follow-up. The driving simulator evaluated reaction times to high and low contrast peripheral divided attention stimuli presented while negotiating a winding country road, with central driving task performance assessed as “curve coherence”. Drivers with MVC during follow-up were identified from Department of Motor Vehicle records.Main Outcome Measures
Survival models were used to evaluate the ability of driving simulator and UFOV to predict MVC over time, adjusting for potential confounding factors.Results
Mean age at baseline was 64.5 ± 12.6 years. 11 of 117 (9.4%) drivers had a MVC during follow-up. In the multivariable models, low contrast reaction time was significantly predictive of MVC, with a hazard ratio (HR) of 2.19 per 1 SD slower reaction time (95% CI, 1.30 to 3.69; P = 0.003). UFOV divided attention was also significantly predictive of MVC with a HR of 1.98 per 1 SD worse (95% CI, 1.10 to 3.57; P = 0.022). Global SAP visual field indices in the better or worse eye were not predictive of MVC. The longitudinal model including driving simulator performance was a better predictor of MVC compared to UFOV (R2 = 0.41 vs R2 = 0.18).Conclusions
Longitudinal divided attention metrics on the UFOV test and during simulated driving were significantly predictive of risk of MVC in glaucoma patients. These findings may help improve the understanding of factors associated with driving impairment related to glaucoma. 相似文献3.
Longhua Yu Liqi Xie Chao Dai Bing Xie Minglong Liang Lu Zhao Xuntao Yin Jian Wang 《PloS one》2015,10(3)
The aim of this study was to investigate possible changes of cortical thickness in the visual cortex in primary open-angle glaucoma (POAG) of varying severity. Twenty normal controls (NC), 20 mild (MP) and 17 severe (SP) POAG patients were recruited and scanned using magnetic resonance imaging. Cortical thickness analyses with regions of interest (V1, V2, ventral V3, V4 and V5/MT+) were used to assess the cortical changes among the three groups. Furthermore, the associations of cortical thickness with retinal nerve fiber layer (RNFL) thickness and mean deviation of visual field were analyzed. Compared with the NC group, decreased cortical thickness was detected in the bilateral V5/MT+ areas in the MP group and the left V1, bilateral V2 and V5/MT+ areas in the SP group. Cortical thinning of the bilateral V2 areas was detected in the SP group compared with the MP group. In addition, cortical thinning of these visual areas was related to the ophthalmologic measurements. In conclusion, POAG patients exhibit cortical thinning in the bilateral V5/MT+ in the early stage of disease. The cortical degeneration in visual areas is discrepant with disease progressing and the dorsal pathway might be selectively damaged in POAG. Therefore, the cortical thinning of these visual areas may play a key role in the progression of POAG and can serve as a novel biomarker for accurately evaluating the severity of POAG. 相似文献
4.
Kyoung Min Lee Tae-Woo Kim Robert N. Weinreb Eun Ji Lee Micha?l J. A. Girard Jean Martial Mari 《PloS one》2014,9(12)
PurposeTo determine using swept-source optical coherence tomography (SS-OCT) whether there are differences in the location of the anterior lamina cribrosa insertion (ALI) in primary open-angle glaucoma (POAG) patients and healthy subjects.MethodsFifty three eyes from 53 patients with POAG, and 53 eyes from 53 age-matched healthy subjects were included prospectively in Seoul National University Bundang Hospital. Twelve radial line B-scans centered on the optic disc in every half-clock-hour meridian were acquired using SS-OCT. The ALI position was assessed by measuring two parameters: (1) ALI distance (ALID)—the distance from the anterior scleral canal opening (ASCO) to the ALI; and (2) marginal anterior lamina cribrosa surface depth (mALCSD)—the perpendicular distance from the ASCO plane to the anterior lamina cribrosa surface. These parameters were compared between the two groups for each meridian.ResultsBoth ALID (256±54 vs. 209±37 µm, mean ± SD, p<0.001) and mALCSD (232±63 vs. 187±40 µm, p<0.001) were significantly greater in the POAG group than in the normal group. The largest difference was observed at the 6.5 o′clock and 11.5 o′clock meridians for both ALID and mALCSD. Multiple regression analysis revealed a negative correlation between age and both ALID and mALCSD in the control group, and a negative correlation between mean deviation of the visual field test and both ALID and mALCSD in the POAG group.ConclusionsThe ALI was displaced posteriorly in eyes with POAG compared to those of healthy controls. This finding suggests that the posteriorly located lamina cribrosa insertion is an important component of glaucomatous optic nerve excavation. 相似文献
5.
Amir H. Marvasti Andrew J. Tatham Linda M. Zangwill Christopher A. Girkin Jeffrey M. Liebmann Robert N. Weinreb Felipe A. Medeiros 《PloS one》2013,8(10)
Purpose
To evaluate the relationship between visual field index (VFI) and the estimated number of retinal ganglion cells (RGCs) in glaucoma.Methods
A multicenter study of 1,245 healthy, glaucomatous and suspected glaucomatous eyes of 1,245 subjects recruited from the Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). All eyes underwent standard automated perimetry (SAP) and time-domain optical coherence tomography (TD-OCT). Estimates of RGC count and percentage of RGCs remaining, compared to age-matched healthy eyes, were calculated from TD-OCT using a previously described formula. Smoothing spline curves were fitted to examine the relationship between VFI and the percent remaining RGCs. The first derivative (i.e., slopes) of these curves was used to explore the relationship between changes in these measures.Results
The relationships between the VFI and both estimated RGC counts and the percent remaining RGCs were nonlinear. A unit number of VFI loss corresponded to substantially greater loss of estimated RGCs and estimated percentage of RGCs remaining in early compared to late disease.Conclusions
The relationship between VFI and estimated RGC counts is nonlinear and the index substantially underestimates the amount of neural loss early in the disease. Disease severity should be taken into account when interpreting rates of VFI change over time. 相似文献6.
7.
Background
The involvement of local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage has been hypothesized in the pathogenesis of glaucoma. To test this, we measured the systemic levels of prooxidants and antioxidants by analyzing the blood biochemistry in patients with glaucoma.Methods
Peripheral blood samples were collected from Japanese patients with primary open-angle glaucoma (PG) (n = 206), exfoliation syndrome (EX) (n = 199), and controls (n = 126). Plasma levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured by diacron reactive oxygen metabolites (dROM), biological antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free radical analyzer.Results
In the PG, EX, and control groups, the mean ± standard deviation values were 355±63, 357±69, and 348±56 (U. Carr), respectively, for dROM; 1,951±282, 1,969±252, and 2,033±252 (µmol/L), respectively, for BAP (µmol/L); and 614±98, 584±91, and 617±99 (µmol/L), respectively, for SH. The differences in the BAP values were significant between the PG and control groups (p = 0.0062), for SH between the EX and control groups (p = 0.0017), and for SH between the PG and EX groups (p = 0.0026). After adjustment for differences in age and sex among groups using multiple regression analysis, lower BAP values were correlated significantly with PG (p = 0.0155) and EX (p = 0.0049). Higher dROM values with and without glaucoma were correlated with female gender, and lower SH values with older age. There were no significant differences between the higher (≥21 mmHg) and lower (<21 mmHg) baseline IOPs in the PG group or between the presence or absence of glaucoma in the EX group.Conclusions
Lower systemic antioxidant capacity that measured by ferric-reducing activity is involved in the pathogenesis of PG and EX. 相似文献8.
Qi Li Ningli Wang Zhicheng Liu Lin Li Zhicheng Liu Wenjia Wang Xiaoxue Long Hongfang Song 《Molecular & cellular biomechanics : MCB》2020,17(3):119-137
Aim: To investigate the relationship between glaucoma and intraocular
pressure (IOP), intracranial pressure (ICP), trans-laminar cribrosa pressure difference (TLCPD), and the newly proposed fractional pressure reserve (FPR). Methods: Ten articles were analyzed by meta-analysis, and subgroup analysis of three
factors was conducted. Results: The patients with normal tension glaucoma
(NTG) and open-angle glaucoma (OAG) have higher TLCPD and lower ICP than
healthy subjects, with obvious heterogeneity. The greater heterogeneity may arise
from different ICP measurements and from different countries or regions. FPR
performs better than TLCPD in some ways. Conclusion: Both FPR and TLCPD
can be used as indicators of NTG and OAG, and FPR is more effective than
TLCPD in comparisons between different experiments or individuals. 相似文献
9.
10.
Purpose
To assess the short-term day-to-day reproducibility of 24-hour intraocular pressure (IOP) curves in various respects in untreated primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients.Methods
47 subjects with POAG and 34 subjects with OHT underwent IOP measurements every 2 hours in both eyes for consecutive 48 hours by a non-contact tonometer (NCT). IOP values at each time point were recorded. Mean IOP, peak IOP, time difference of peak IOP between two days and IOP fluctuation were also calculated. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to evaluate reproducibility.Results
ICCs of the entire IOP values for a complete 24-hour curve were 0.577 and 0.561 in POAG and OHT patients, respectively. ICCs of IOP values at different time points ranged from 0.384 (10am) to 0.686 (4am) in POAG patients and from 0.347 (6am) to 0.760 (4am) in OHT patients. ICCs of mean IOP, peak IOP and IOP fluctuation were respectively 0.832, 0.704, 0.367 in POAG patients and 0.867, 0.816 0.633 in OHT patients. Only 37.23% and 35.29% of the peak IOP time points appeared within the time difference of 2 hours in POAG and OHT patients, respectively, while 53.19% and 48.53% appeared within 4 hours in POAG and OHT patients, respectively.Conclusion
A 24-hour IOP curve in a single day is not highly reproducible in short-term and has limited use for evaluating individual IOP condition. Mean IOP and peak IOP for a 24-hour IOP curve are useful parameters in clinical follow-up, while IOP value at a certain time point, IOP fluctuation and peak IOP time point should be interpreted with caution. 相似文献11.
Megan Ulmer Carnes Yangfan P. Liu R. Rand Allingham Benjamin T. Whigham Shane Havens Melanie E. Garrett Chunyan Qiao NEIGHBORHOOD Consortium Investigators Nicholas Katsanis Janey L. Wiggs Louis R. Pasquale Allison Ashley-Koch Edwin C. Oh Michael A. Hauser 《PLoS genetics》2014,10(5)
Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) is the most common subtype and is a complex trait with multigenic inheritance. Genome-wide association studies have previously identified a significant association between POAG and the SIX6 locus (rs10483727, odds ratio (OR) = 1.32, p = 3.87×10−11). SIX6 plays a role in ocular development and has been associated with the morphology of the optic nerve. We sequenced the SIX6 coding and regulatory regions in 262 POAG cases and 256 controls and identified six nonsynonymous coding variants, including five rare and one common variant, Asn141His (rs33912345), which was associated significantly with POAG (OR = 1.27, p = 4.2×10−10) in the NEIGHBOR/GLAUGEN datasets. These variants were tested in an in vivo Danio rerio (zebrafish) complementation assay to evaluate ocular metrics such as eye size and optic nerve structure. Five variants, found primarily in POAG cases, were hypomorphic or null, while the sixth variant, found only in controls, was benign. One variant in the SIX6 enhancer increased expression of SIX6 and disrupted its regulation. Finally, to our knowledge for the first time, we have identified a clinical feature in POAG patients that appears to be dependent upon SIX6 genotype: patients who are homozygous for the SIX6 risk allele (His141) have a statistically thinner retinal nerve fiber layer than patients homozygous for the SIX6 non-risk allele (Asn141). Our results, in combination with previous SIX6 work, lead us to hypothesize that SIX6 risk variants disrupt the development of the neural retina, leading to a reduced number of retinal ganglion cells, thereby increasing the risk of glaucoma-associated vision loss. 相似文献
12.
Francesca Pasutto Christian Y. Mardin Johann H. Brandstätter Nicole Weisschuh Wishal D. Ramdas Leonieke M.E. van Koolwijk Johannes R. Vingerling Bernhard H.F. Weber Bernd Rautenstrauss Yves-Alain Barde 《American journal of human genetics》2009,85(4):447-456
Glaucoma, a main cause of blindness in the developed world, is characterized by progressive degeneration of retinal ganglion cells (RGCs), resulting in irreversible loss of vision. Although members of the neurotrophin gene family in various species are known to support the survival of numerous neuronal populations, including RGCs, it is less clear whether they are also required for survival and maintenance of adult neurons in humans. Here, we report seven different heterozygous mutations in the Neurotrophin-4 (NTF4) gene accounting for about 1.7% of primary open-angle glaucoma patients of European origin. Molecular modeling predicted a decreased affinity of neurotrophin 4 protein (NT-4) mutants with its specific tyrosine kinase receptor B (TrkB). Expression of recombinant NT-4 carrying the most frequent mutation was demonstrated to lead to decreased activation of TrkB. These findings suggest a pathway in the pathophysiology of glaucoma through loss of neurotrophic function and may eventually open the possibility of using ligands activating TrkB to prevent the progression of the disease. 相似文献
13.
Jost B. Jonas Vinay Nangia Ningli Wang Karishma Bhate Prabhat Nangia Purna Nangia Diya Yang Xiaobin Xie Songhomitra Panda-Jonas 《PloS one》2013,8(12)
Purpose
To assess associations of the trans-lamina cribrosa pressure difference (TLCPD) with glaucomatous optic neuropathy.Methods
The population-based Central India Eye and Medical Study included 4711 subjects. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg] = 0.44 Body Mass Index[kg/m2]+0.16 Diastolic Blood Pressure[mmHg]−0.18×Age[Years] −1.91. TLCPD was IOP–CSFP.Results
Mean TLCPD was 3.64±4.25 mm Hg in the non-glaucomatous population and 9.65±8.17 mmHg in the glaucomatous group. In multivariate analysis, TLCPD was associated with older age (P<0.001; standardized coefficient beta:0.53; regression coefficient B:0.18; 95% confidence interval (CI):0.17, 0.18), lower body mass index (P<0.001; beta: −0.28; B: −0.36; 95%CI: −0.38, −0.31), lower diastolic blood pressure (P<0.001; beta: −0.31; B: −0.12; 95%CI: −0.13, −0.11), higher pulse (P<0.001; beta:0.05; B:0.02; 95%CI:0.01,0.2), lower body height (P = 0.02; beta: −0.02; B: −0.01; 95%CI: −0.02,0.00), higher educational level (P<0.001; beta:0.04; B:0.15; 95%CI:0.09,0.22), higher cholesterol blood concentrations (P<0.001; beta:0.04; B:0.01; 95%CI:0.01,0.01), longer axial length (P = 0.006; beta:0.03; B:0.14; 95%CI:0.04,0.24), thicker central cornea (P<0.001; beta:0.15; B:0.02; 95%CI:0.02,0.02), higher corneal refractive power (P<0.001; beta:0.07; B:0.18; 95%CI:0.13,0.23) and presence of glaucomatous optic neuropathy (P<0.001; beta:0.11; B:3.43; 95%CI:2.96,3.99). Differences between glaucomatous subjects and non-glaucomatous subjects in CSFP were more pronounced for open-angle glaucoma (OAG) than for angle-closure glaucoma (ACG) (3.0 mmHg versus 1.8 mmHg), while differences between glaucomatous subjects and non-glaucomatous subjects in IOP were higher for ACG than for OAG (8.5 mmHg versus 3.0 mmHg). Presence of OAG was significantly associated with TLCPD (P<0.001; OR:1.24; 95%CI:1.19,1.29) but not with IOP (P = 0.08; OR:0.96; 95%CI:0.91,1.00). Prevalence of ACG was significantly associated with IOP (P = 0.04; OR:1.19; 95%CI:1.01,1.40) but not with TLCPD (P = 0.92).Conclusions
In OAG, but not in ACG, calculated TLCPD versus IOP showed a better association with glaucoma presence and amount of glaucomatous optic neuropathy. It supports the notion of a potential role of low CSFP in the pathogenesis of open-angle glaucoma. 相似文献14.
Background
Glaucoma is the leading cause of irreversible blindness in the world. Recent evidence indicates a role for genetic susceptibility to primary open-angle glaucoma (POAG). The relation between myocilin polymorphisms and POAG susceptibility has been studied in different populations.Methods
A meta-analysis of 32 published genetic association case-control studies, which examined the relation between POAG and the R46X, R76K, Y347Y, T353I, and Q368X polymorphisms of the myocilin gene, was carried out.Results
In meta-analysis, significant associations were observed between POAG risk and two myocilin polymorphisms with summarized odds ratio of 4.68 (95%CI, 2.02–10.85) for Q368X and 2.17 (95% CI, 1.32–3.57) for T353I. Both Q368X and T353I were significantly associated with high-tension glaucoma, with summarized odds ratio of 4.26 (1.69, 10.73) and 2.26 (1.37–3.72). In Westerners, significant association was observed for Q368X mutation (odds ratio, 5.17; 95% CI, 2.16–12.40). However, in Asians it was for T353I (odds ratio, 2.17; 95% CI, 1.32–3.57).Conclusions
There is strong evidence that myocilin polymorphisms are associated with POAG susceptibility, and the prevalence of myocilin mutations might be ethnicity-dependent in Caucasians for Q368X and in Asians for T353I. 相似文献15.
Yong Woo Kim Jin Wook Jeoung Dai Woo Kim Michael J. A. Girard Jean Martial Mari Ki Ho Park Dong Myung Kim 《PloS one》2016,11(3)
Purpose
Quantitative evaluation of lamina cribrosa (LC) posterior bowing in primary open-angle glaucoma (POAG) eyes using swept-source optical coherence tomography.Methods
Patients with POAG (n = 123 eyes) and healthy individuals of a similar age (n = 92 eyes) were prospectively recruited. Anterior laminar insertion depth (ALID) was defined as the vertical distance between the anterior laminar insertion and a reference plane connecting the Bruch’s membrane openings (BMO). The mean LC depth (mLCD) was approximated by dividing the area enclosed by the anterior LC, the BMO reference plane, and the two vertical lines for ALID measurement by the length between those two vertical lines. The LC curvature index was defined as the difference between the mLCD and the ALID. The factors influencing the LC curvature index were evaluated.Results
The ALID and mLCD were significantly larger in POAG eyes than in healthy controls (P < 0.05). The LC curvature index was significantly larger in POAG eyes than in healthy controls on both the horizontal (85.8 ± 34.1 vs. 68.2 ± 32.3 μm) and vertical meridians (49.8 ± 38.5 vs. 32.2 ± 31.1 μm, all P < 0.001). Multivariate regression showed significant associations of greater disc area (P < 0.001), vertical C/D ratio (P < 0.001) and mLCD (P < 0.001), smaller rim area (P = 0.001), thinner average RNFLT (P < 0.001), and myopic refraction (P = 0.049) with increased LC curvature index. There was no difference in the LC curvature index between mild (MD > –6 dB) and moderate-to-advanced glaucoma (MD < –6 dB, P = 0.95).Conclusions
LC posterior bowing was increased in POAG eyes, and was significantly associated with structural optic nerve head (ONH) changes but not with functional glaucoma severity. Quantitative evaluation of LC curvature can facilitate assessment of glaucomatous ONH change. 相似文献16.
Main Objective
The thinning of prelaminar tissue and prelamina cupping is known to occur by ischemia, as we see in anterior ischemic optic neuropathy. Since normal tension glaucoma (NTG) is thought to be more related to vascular factor than in primary open-angle glaucoma (POAG), we hypothesized that prelamina thinning may occur prominently in NTG patients. This study investigated the difference in prelaminar tissue thickness between patients with POAG and NTG and verified the factors related to prelaminar thinning.Methods
Complete ophthalmic examination including standard automatic perimetry was performed in all patients. The prelaminar tissue thickness was measured in all patients by performing enhanced depth imaging with a Heidelberg Spectralis Optical Coherence Tomography. The retinal nerve fiber layer and optic nerve head parameters were obtained using the Heidelberg Retina Tomography II and Cirrus Optical Coherence Tomography. Various ocular factors and their relationships with prelaminar thickness were analyzed.Results
The mean prelaminar tissue thickness was significantly thinner in patients with POAG than in those with NTG. The difference in the prelaminar thickness between patients with POAG and those with NTG was greater in the early field defect group than in the moderate and severe field groups. In multivariate analysis, the mean prelaminar thickness was related to the intraocular pressure, mean deviation, cup-disc ratio, and cup volume.Conclusions
The prelaminar tissue was thinner in patients with POAG than in patients with NTG, and intraocular pressure had a strong influence on the prelaminar thickness in both POAG and NTG. This may indicate that mechanical compression is the main pathogenic factor in both POAG and NTG. 相似文献17.
Nicole J Van Bergen Jonathan G. Crowston Jamie E. Craig Kathryn P. Burdon Lisa S. Kearns Shiwani Sharma Alex W. Hewitt David A. Mackey Ian A. Trounce 《PloS one》2015,10(10)
Primary Open Angle Glaucoma (POAG) is a common neurodegenerative disease characterized by the selective and gradual loss of retinal ganglion cells (RGCs). Aging and increased intraocular pressure (IOP) are glaucoma risk factors; nevertheless patients deteriorate at all levels of IOP, implying other causative factors. Recent evidence presents mitochondrial oxidative phosphorylation (OXPHOS) complex-I impairments in POAG. Leber Hereditary Optic Neuropathy (LHON) patients suffer specific and rapid loss of RGCs, predominantly in young adult males, due to complex-I mutations in the mitochondrial genome. This study directly compares the degree of OXPHOS impairment in POAG and LHON patients, testing the hypothesis that the milder clinical disease in POAG is due to a milder complex-I impairment. To assess overall mitochondrial capacity, cells can be forced to produce ATP primarily from mitochondrial OXPHOS by switching the media carbon source to galactose. Under these conditions POAG lymphoblasts grew 1.47 times slower than controls, whilst LHON lymphoblasts demonstrated a greater degree of growth impairment (2.35 times slower). Complex-I enzyme specific activity was reduced by 18% in POAG lymphoblasts and by 29% in LHON lymphoblasts. We also assessed complex-I ATP synthesis, which was 19% decreased in POAG patients and 17% decreased in LHON patients. This study demonstrates both POAG and LHON lymphoblasts have impaired complex-I, and in the majority of aspects the functional defects in POAG were milder than LHON, which could reflect the milder disease development of POAG. This new evidence places POAG in the spectrum of mitochondrial optic neuropathies and raises the possibility for new therapeutic targets aimed at improving mitochondrial function. 相似文献
18.
Janey L. Wiggs Alex W. Hewitt Bao Jian Fan Dan Yi Wang Dayse R. Figueiredo Sena Colm O’Brien Anthony Realini Jamie E. Craig David P. Dimasi David A. Mackey Jonathan L. Haines Louis R. Pasquale 《PloS one》2012,7(9)
Background
Loss of vision in glaucoma is due to apoptotic retinal ganglion cell loss. While p53 modulates apoptosis, gene association studies between p53 variants and glaucoma have been inconsistent. In this study we evaluate the association between a p53 variant functionally known to influence apoptosis (codon 72 Pro/Arg) and the subset of primary open angle glaucoma (POAG) patients with early loss of central visual field.Methods
Genotypes for the p53 codon 72 polymorphism (Pro/Arg) were obtained for 264 POAG patients and 400 controls from the U.S. and in replication studies for 308 POAG patients and 178 controls from Australia (GIST). The glaucoma patients were divided into two groups according to location of initial visual field defect (either paracentral or peripheral). All cases and controls were Caucasian with European ancestry.Results
The p53-PRO/PRO genotype was more frequent in the U.S. POAG patients with early visual field defects in the paracentral regions compared with those in the peripheral regions or control group (p = 2.7×10−5). We replicated this finding in the GIST cohort (p = 7.3×10−3, and in the pooled sample (p = 6.6×10−7) and in a meta-analysis of both the US and GIST datasets (1.3×10−6, OR 2.17 (1.58–2.98 for the PRO allele).Conclusions
These results suggest that the p53 codon 72 PRO/PRO genotype is potentially associated with early paracentral visual field defects in primary open-angle glaucoma patients. 相似文献19.
Hiroshi Murata Hiroyo Hirasawa Yuka Aoyama Kenji Sugisaki Makoto Araie Chihiro Mayama Makoto Aihara Ryo Asaoka 《PloS one》2013,8(3)
PurposeThe purpose of this study was to create a vision-related quality of life (VRQoL) prediction system to identify visual field (VF) test points associated with decreased VRQoL in patients with glaucoma.MethodVRQoL score was surveyed in 164 patients with glaucoma using the ‘Sumi questionnaire’. A binocular VF was created from monocular VFs by using the integrated VF (IVF) method. VRQoL score was predicted using the ‘Random Forest’ method, based on visual acuity (VA) of better and worse eyes (better-eye and worse-eye VA) and total deviation (TD) values from the IVF. For comparison, VRQoL scores were regressed (linear regression) against: (i) mean of TD (IVF MD); (ii) better-eye VA; (iii) worse-eye VA; and (iv) IVF MD and better- and worse-eye VAs. The rank of importance of IVF test points was identified using the Random Forest method.ResultsThe root mean of squared prediction error associated with the Random Forest method (0.30 to 1.97) was significantly smaller than those with linear regression models (0.34 to 3.38, p<0.05, ten-fold cross validation test). Worse-eye VA was the most important variable in all VRQoL tasks. In general, important VF test points were concentrated along the horizontal meridian. Particular areas of the IVF were important for different tasks: peripheral superior and inferior areas in the left hemifield for the ‘letters and sentences’ task, peripheral, mid-peripheral and para-central inferior regions for the ‘walking’ task, the peripheral superior region for the ‘going out’ task, and a broad scattered area across the IVF for the ‘dining’ task.ConclusionThe VRQoL prediction model with the Random Forest method enables clinicians to better understand patients’ VRQoL based on standard clinical measurements of VA and VF. 相似文献
20.
Nai-Wen Fan De-Kuang Hwang Yu-Chieh Ko Fan-Chen Tseng Kuo-Hsuan Hung Catherine Jui-Ling Liu 《PloS one》2013,8(7)