AIM:To explore the DNA methylation of COL4A1 in ultraviolet-B(UVB)-induced age-related cataract(ARC)models in vitro and in vivo.METHODS:Human lens epithelium B3(HLEB3)cells and Sprague Dawley rats were exposure to UVB...AIM:To explore the DNA methylation of COL4A1 in ultraviolet-B(UVB)-induced age-related cataract(ARC)models in vitro and in vivo.METHODS:Human lens epithelium B3(HLEB3)cells and Sprague Dawley rats were exposure to UVB respectively.The MTT assay was utilized to evaluate cell proliferation.Flow cytometry was employed for analysis of cell apoptosis and cell cycle.COL4A1 expression in HLEB3 cells and anterior lens capsules were assessed using Western blot and reverse transcription-polymerase chain reaction(RTPCR).The localization of COL4A1 in HLEB3 cells was determined by immunofluorescence.The methylation status of CpG islands located in COL4A1 promoter was verified using bisulfite-sequencing PCR(BSP).DNMTs and TETs mRNA levels was examined by RT-PCR.RESULTS:UVB exposure decreased HLEB3 cells proliferation,while increased the apoptosis rate and cells were arrested in G0/G1 phase.COL4A1 expression was markedly inhibited in UVB treated cells compared to the controls.Hypermethylation status was detected in the CpG islands within COL4A1 promoter in HLEB3 cells subjected to UVB exposure.Expressions of DNMTs including DNMT1/2/3 were elevated in UVB treated HLEB3 cells compared to that in the controls,while expressions of TETs including TET1/2/3 showed the opposite trend.Results from the UVB treated rat model further confirmed the decreased expression of COL4A1,hypermethylation status of the CpG islands at promoter of COL4A1 and abnormal expression of DNMT1/2/3 and TET1/2/in UVB exposure group.CONCLUSION:DNA hypermethylation of COL4A1 promoter CpG islands is correlated with decreased COL4A1 expression in UVB induced HLEB3 cells and anterior lens capsules of rats.展开更多
BACKGROUND The importance of age on the development of ocular conditions has been reported by numerous studies.Diabetes may have different associations with different stages of ocular conditions,and the duration of di...BACKGROUND The importance of age on the development of ocular conditions has been reported by numerous studies.Diabetes may have different associations with different stages of ocular conditions,and the duration of diabetes may affect the development of diabetic eye disease.While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality,whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored.It is unclear which types of diabetes are more predictive of ocular conditions.AIM To examine associations between the age of diabetes diagnosis and the incidence of cataract,glaucoma,age-related macular degeneration(AMD),and vision acuity.METHODS Our analysis was using the UK Biobank.The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis,and 6689 diabetic participants and 13378 controls for vision analysis.Ocular diseases were identified using inpatient records until January 2021.Vision acuity was assessed using a chart.RESULTS During a median follow-up of 11.0 years,3874,665,and 616 new cases of cataract,glaucoma,and AMD,respectively,were identified.A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age.Individuals with type 2 diabetes(T2D)diagnosed at<45 years[HR(95%CI):2.71(1.49-4.93)],45-49 years[2.57(1.17-5.65)],50-54 years[1.85(1.13-3.04)],or 50-59 years of age[1.53(1.00-2.34)]had a higher risk of AMD independent of glycated haemoglobin.T2D diagnosed<45 years[HR(95%CI):2.18(1.71-2.79)],45-49 years[1.54(1.19-2.01)],50-54 years[1.60(1.31-1.96)],or 55-59 years of age[1.21(1.02-1.43)]was associated with an increased cataract risk.T2D diagnosed<45 years of age only was associated with an increased risk of glaucoma[HR(95%CI):1.76(1.00-3.12)].HRs(95%CIs)for AMD,cataract,and glaucoma associated with type 1 diabetes(T1D)were 4.12(1.99-8.53),2.95(2.17-4.02),and 2.40(1.09-5.31),respectively.In multivariable-adjusted analysis,individuals with T2D diagnosed<45 years of age[β95%CI:0.025(0.009,0.040)]had a larger increase in LogMAR.Theβ(95%CI)for LogMAR associated with T1D was 0.044(0.014,0.073).CONCLUSION The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.展开更多
AIM:To evaluate the regulation of the aberrant expression of collagen typeⅣalpha 1 chain(COL4A1)in the development of age-related cataract(ARC).METHODS:Quantitative reverse transcription-polymerase chain reaction(qRT...AIM:To evaluate the regulation of the aberrant expression of collagen typeⅣalpha 1 chain(COL4A1)in the development of age-related cataract(ARC).METHODS:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and Western blot analysis were employed to evaluate the expression of COL4A1 in ARC patients and healthy controls.The proliferation,apoptosis,cell cycle and epithelial-mesenchymal transition(EMT)of human lens epithelial cell(HLE-B3)were further analyzed under the condition of COL4A1 gene silence.Alteration of gene expression at mRNA level after knockdown COL4A1 were also evaluated by qRT-PCR on HLE-B3 cells.RESULTS:The aberrant expression of COL4A1 was identified a clinically associated with the ARC.Silencing of COL4A1 promoted the apoptosis and inhibited the proliferation of HLE-B3 by blocking the cell cycle.Moreover,COL4A1 gene silence didn’t affect the cytoskeleton of HLE-B3 but down-regulated the Collagen typeⅣAlpha 2 Chain(COL4A2),paired box 6(PAX6),procollagen-lysine 2-oxoglutarate 5-dioxygenases 1(PLOD1)and procollagenlysine 2-oxoglutarate 5-dioxygenases 2(PLOD2)expression levels in HLE-B3 cells.Silencing the COL4A1 gene induced EMT of the HLE-B3 cells by promoting the transforming growth factor beta(TGF-β)expression.CONCLUSION:Silencing of COL4A1 induces S-phase arrest,also inhibits the proliferation and enhance HLE-B3 apoptosis and EMT,and down-regulates the expression of COL4A2,PAX6,PLOD1 and PLOD2.Thus,the expression alteration of COL4A1 may play a critical role in the pathogenesis of ARC.展开更多
Objective:Age-relate cataract(ARC)is a disease of the eyes with no effective drugs to prevent or treat patients.The aim of the present study is to determine whether histone H3,αA-crystallin(CRYAA),β-galactosidase(GL...Objective:Age-relate cataract(ARC)is a disease of the eyes with no effective drugs to prevent or treat patients.The aim of the present study is to determine whether histone H3,αA-crystallin(CRYAA),β-galactosidase(GLB1),and p53 are involved in the pathogenesis of ARC.Methods:A total of 99 anterior lens capsules(ALCs)of patients with ARC of various nuclear grades,ultraviolet models of ALCs,and two human lens epithelial cell lines(FHL-124 and SRA01/04)were used,and the expression of histone H3,CRYAA,GLB1,and p53 were detected by immunoblotting and reverse transcription and real time-quantitative polymerase chain reaction.The association between CRYAA with histone H3,GLB1,and p53 was assessed in FHL-124 and SRA01/04 cells following CRYAA overexpression.Results:Histone H3 and p53 in ALCs of patients with ARC were up-regulated in a grade-dependent manner,and the expression of CRYAA showed a positive association with histone H3,p53,and GLB1.In UV models of ALCs and human lens epithelial cell lines,the expression levels of histone H3,cell apoptosis factors(Bax/Bcl-2,cleaved caspase-3),and inflammation factors(interleukin-6,tumor necrosis factor-α)were all up-regulated.Furthermore,transfection of CRYAA in FHL-124 cells induced overexpression of histone H3.Conclusion:CRYAA-mediated upregulation of histone H3 may be involved in the pathogenesis of ARC.p53 may also have a role in ARC development,but not via the CRYAA-histone H3 axis.The results of the present study may assist in improving our understanding of the pathogenesis of ARC and in identifying potential targets for treatment.展开更多
AIM: To determine the association between cigarettes smoking, body mass index (BMI) and the risk of age-related cataract (ARC) in middle-aged and elderly men in Northeast China. METHODS: A hospital-based case control ...AIM: To determine the association between cigarettes smoking, body mass index (BMI) and the risk of age-related cataract (ARC) in middle-aged and elderly men in Northeast China. METHODS: A hospital-based case control study was conducted. Cases (n =362) were men who had surgically treated ARC, 45-85 years old; controls frequency-matched (n=362) were men who had been admitted to the same hospital as cases for other diseases not related with eye diseases. Cases and controls were matched with 1:1. The cases and controls were interviewed during their hospital stay, using a structured interviewer-administrated questionnaire that included information on sociodemographic characteristics, socioeconomic, lifestyle habits (tobacco smoking and alcohol consumption, etc.), anthropometric measures, personal medical history, and family history of ARC in first-degree relatives, and simultaneously BMI was calculated. The odds ratios (OR) and 95% confidence intervals (CI) of ARC were estimated using multiple logistic regression models. RESULTS: After adjusting for age and multiple potential confounders, higher BMI was associated with an increased risk of ARC. Cigarette smoking, years smoking or moderate cigarette smoking (1-29 cigarettes per day) had no relation with the risk of ARC (P>0.05), although patients smoking >= 30 cigarettes per day had an elevated risk of ARC as compared with the non-smokers (OR=1.55, 95% CI; 1.16-2.85, P=0.026). Higher BMI was associated with an increased risk of ARC. Both overweight and obesity was associated with an obviously increased risk for surgically ARC (OR=1.55, 95% CI:1.02-1.98, P=0.015 and OR=1.71, 95% CI:1.32-2.39, P=0.013 respectively) compared to normal BMI. Then participants were grouped into quartiles of BMI (Q1 to Q4), compared to controls in the lowest quartile, the ORfor cases in the highest quartile of BMI was 1.54 (OR=1.54, 95% CI: 1.08-2.46, P=0.022). The results of univariate analysis showed cigarette smoking was not associated with ARC formation for men with lower or normal BMI (P >0.05). Compared to the non-smokers, for men of overweight or obesity, cigarette smoking was associated with a significantly increased risk for surgically ARC (OR=2.00, 95% CI: 1.49-6.65, P=0.003 and OR=1.66, 95% CI: 1.63-13.21, P=0.002 respectively). Similarly, smokers in the highest quartile of BMI had approximately 1.5 times the risk of ARC as non-smokers in the lowest quartile (OR =1.46, 95% CI: 1.06-5.29, P<0.001). Followed multivariate models revealed that the association had never changed. CONCLUSION: Current cigarette smoking is positively related to ARC only among those who smoking 30 or more cigarettes per day. For men who are both overweight and obesity, cigarette smoking is associated with a significantly increased risk for ARC.展开更多
AIM:To investigate the prevalence and risk factors of age-related cataract(ARC),ARC surgery procedures,and postoperative vision results among adults over 50 years old in the Binhu District of Wuxi City,China.METHODS:T...AIM:To investigate the prevalence and risk factors of age-related cataract(ARC),ARC surgery procedures,and postoperative vision results among adults over 50 years old in the Binhu District of Wuxi City,China.METHODS:Thirty basic sampling units were analyzed via a cluster random sampling method.Detailed medical histories were collected and eye examinations were performed.Cataract prevalence and surgical procedures were quantified.RESULTS:Among the 6150 participants,1421 cataract cases were diagnosed and prevalence was 23.1%.The prevalence of cortical,nuclear,and posterior subcapsular cataracts increased with age(P<0.001).Cataract prevalence was significantly higher among elderly,female,or illiterate individuals and people with hypertension,diabetes,and a history of smoking and drinking(all P<0.05).As participant age increased and education level decreased,the frequency of cataract blindness surgeries gradually decreased,but without statistical significance within groups(P>0.05).The odds ratio of cataract patients who had or did not have cataract surgery was 3.15(87/28)and the frequency of cataract blindness surgery was 75.7%(87/115).Poor visual outcomes was in 107 eyes(40.7%)after cataract surgery.Poor vision was mostly caused by uncorrected reflective errors(30.9%)and ocular comorbidities(41.1%).The prevalence of cataract surgery complications was 5.7%(15/263).Surgical complications and posterior capsular opacification were avoidable factors facilitating poor vision.CONCLUSION:ARC,especially in females and illiterateindividuals,presents a public health problem in this district.Poor visual outcomes after cataract surgery are frequent.High-quality cataract surgeries and treatment of ocular comorbidities are vital.展开更多
AIM:To examine the association between dietary macronutrient intake and the risk of age-related cataract(ARC)in middle-aged and elderly men.METHODS:A hospital-based case-control study was conducted from December 2009 ...AIM:To examine the association between dietary macronutrient intake and the risk of age-related cataract(ARC)in middle-aged and elderly men.METHODS:A hospital-based case-control study was conducted from December 2009 to November 2011.Cases(n=360)were patients with cataract aged 45-85years old,and controls(n=360)were patients who had been admitted to the same hospital for diseases not related with cataract.All subjects were interviewed using a structured interviewer-administrated questionnaire that included information on socio-demographic characteristics,lifestyle habits and detailed medical history,simultaneously,the dietary intakes of nutrients were collected via a valid semi-quantitative food frequency questionnaire(FFQ).The odds ratios(OR)and corresponding 95%confidence intervals(CI)of three types of ARC were estimated using multiple logistic regression models.RESULTS:After adjusting for multiple potential confounders,total dietary intake of carbohydrate was positively associated with cortical cataract,compared to controls in the lowest quartile,and the OR for cases in the highest quartile of intake was 2.471(95%CI:1.348-6.043,P=0.027).Higher dietary intakes of protein were protective for posterior subcapsular cataract(PSC)(OR=0.528,95%CI:0.148-0.869,P=0.023).Dietary fat intake was not associated with any type of cataract,however,participants in the highest quartile of polyunsaturated fatty acids intake had 2.7 times the risk of nuclear cataract as did those in the lowest quartile(OR=2.742,95%CI:1.790-4.200,P=0.033).CONCLUSION:A high intake of carbohydrate and polyunsaturated fatty acid may increase the odds of cortical and nuclear cataract,respectively,whereas high intake of protein,especially animal protein,may protect against PSC cataract.It is possible that dietary changes of target population may reduce the risk of ARC.展开更多
AIM: To investigate the effects and mechanism of miR-211 in mediating the antioxidant function of lens epithelial cells affected by age-related cataracts. METHODS: Real-time quantitative polymerase chain reaction ...AIM: To investigate the effects and mechanism of miR-211 in mediating the antioxidant function of lens epithelial cells affected by age-related cataracts. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect miR-211 expression in the anterior lens capsules of healthy people, the anterior lens capsules of patients with age-related cataracts, and human epithelial cell line (SRA01/04) cells exposed to oxidative stress. A 2', 7'-dichloro-fluorescein diacetate (DCFH-DA) probe was used to measure the levels of endogenous reactive oxygen species (ROS) in human lens epithelial cells (hLECs) exposed to 400 pmol/L H2O2 for lh. SRA01/04 cells were transfected with either miR-211 mimics, mimic controls, miR-211 inhibitors or inhibitor controls. After 72h, these cells were exposed to 400 IJmollL H2O2 for lh, then p53 and Bax mRNA expression were measured using RT-qPCR. p53 and Bax protein expression were also measured by Western blotting analysis. Finally, cell viability was assessed using an MTS assay. RESULTS: Compared to the control group, expression of miR-211 in the anterior lens capsules of age-related cataract patients and in SRA01/04 cells exposed to oxidative stress was significantly increased (P〈0.001). Levels of endogenous ROS were significantly elevated in hLECs exposed to oxidative stress (P〈0.001). Compared to the mimic control group, the hLECs in the miR-211 mimic group expressed significantly higher levels of p53 and Bax mRNA and protein while cell viability was significantly reduced (P〈0.001). Conversely, p53 and Bax mRNA and protein expression were significantly reduced in the miR-211 inhibitor group as compared to the control group, while the cells in this group had much higher levels of call viability (P〈0.001). CONCLUSION: miR-211 is upregulatsd in the anterior lens capsules of age-related cataract patients, miR-211 decreased the antioxidative stress capacity of lens epithelial cells by upregulating p53 and Bax, while inhibiting cell proliferation and repair. This finding suggests that miR-211 may play a key role in the development of age-related cataracts.展开更多
AIM: To determine the association of gap junction protein alpha 3(GJA3) gene tag single-nucleotide polymorphisms(SNPs) with susceptibility to age-related cataract(ARC).METHODS: In total, 486 ARC patients were matched ...AIM: To determine the association of gap junction protein alpha 3(GJA3) gene tag single-nucleotide polymorphisms(SNPs) with susceptibility to age-related cataract(ARC).METHODS: In total, 486 ARC patients were matched with 500 healthy controls. All the participants underwent complete ophthalmic examinations. Haplotype-tagging SNPs of GJA3 gene were selected from the HapMap Beijing Han Chinese population. Genomic DNA was extracted from the peripheral blood leukocytes of all the subjects.Under three different genetic models: dominant, recessive,and additive, the association between SNPs and ARC was examined. After adjusting for age and sex, the genetic effects of the GJA3 SNPs were evaluated with logistic regression analysis.RESULTS: Four tag GJA3 SNPs(rs6490519, rs9506430,rs9509053, and rs9552089) were included in the present study. None of the SNPs showed a significant relationship with an altered risk of total ARC under the dominant,recessive, or additive models. In the subgroup analysis,rs9506430 had a significant effect on the formation of a posterior subcapsular cataract(P=0.002, OR: 0.227, 95%CI:0.088-0.590) under the recessive model.CONCLUSION: Our study indicates that GJA3 variants may influence the development of posterior subcapsular cataracts. Further studies need to be designed to confirm this possibility.展开更多
AIM: To summarize quantitatively the prospective association between physical activity and age-related cataract(ARC) risk.METHODS: Pub Med, Embase, Web of Science, and Cochrane Library were systematically searched for...AIM: To summarize quantitatively the prospective association between physical activity and age-related cataract(ARC) risk.METHODS: Pub Med, Embase, Web of Science, and Cochrane Library were systematically searched for all relevant follow up studies until July 2019. Multivariableadjusted relative risks(RRs) and corresponding 95% confidence intervals(CIs) from individual studies were used to calculate the overall summary estimates. The doseresponse relationship was assessed using generalized least-squares trend estimation.RESULTS: Six prospective cohort studies, involving 19 173 cases in 6.2-12.1 y follow up of 171 620 participants, were included in the analysis. Increased physical activity was significantly associated with reduced risk of ARC by 10%(RR: 0.90;95%CI: 0.81, 0.99, P=0.04). Stratified analysis by assessment method for physical activity suggest that studies using metabolic equivalent(MET) per day tended to report a slightly stronger association with ARC(RR: 0.85;95%CI: 0.81, 0.90, P<0.001) than studies which assessed activity by weekly activity(RR: 0.96;95%CI: 0.89, 1.03, P=0.24). Dose-response analysis indicated that the risk of ARC decreased by 2%(RR: 0.98;95%CI: 0.98, 0.99, P<0.001) for every 6 METs per day increase in activity.CONCLUSION: The findings from this Meta-analysis provide additional evidence that increased physical activity is inversely associated with ARC risk dose-responsively.展开更多
AIM:To explore the susceptible association between the insulin-like growth factor-1 receptor(IGF1 R)single nucleotide polymorphism(SNP)and age-related cataract(ARC),and investigate the underlying mechanisms in human l...AIM:To explore the susceptible association between the insulin-like growth factor-1 receptor(IGF1 R)single nucleotide polymorphism(SNP)and age-related cataract(ARC),and investigate the underlying mechanisms in human lens epithelium(HLE)cells.METHODS:Totally 1190 unrelated participants,comprising 690 ARC patients and 500 healthy individuals in Han Chinese population were recruited and genotyped for target SNP.Theχ2-test was used to detect genotypic distribution between the patient and control groups and the logistic regression was performed to adjust the age and gender.Meanwhile,different biological experimental methods,such as cell counting kit 8(CCK-8)assay,flow cytometry,quantitative real time polymerase chain reaction(Q-PCR)and Western blot,were used to detect cell viability,cell cycle progression and apoptosis in HLE cells or IGF1 R knockdown HLE cells.RESULTS:The rs1546713 in IGF1 R gene was identified(P=0.046,OR:1.606,95%CI:1.245-2.071),which shown a significant relevance with ARC risk under the dominant model.The results demonstrated that IGF1 R knockdown inhibited cell proliferation by inducing cell cycle arrested at S phase and promoting apoptosis.Mechanistically,the cell cycle blocked at S phase was linked with the alterations of cyclin A,cyclin B,cyclin E and P21.The pro-apoptosis function of IGF1 R may related with stimulating the activation of Caspase-3 and altering the expression levels of apoptotic proteins,including Bcl-2,Bax and Caspase-3.CONCLUSION:This study first report that IGF1 R polymorphisms may affect susceptibility to ARCs in Han Chinese population and provide new clues to understand the pathogenic mechanism of ARCs.Notably,IGF1 R is likely a potential target for ARC prevention and treatment.展开更多
AIM: To analyze and screen the methylation status of whole-genome in age-related cataract samples. METHODS: Anterior lens capsule samples were collected from age-related cortical cataract patients over 50 years of a...AIM: To analyze and screen the methylation status of whole-genome in age-related cataract samples. METHODS: Anterior lens capsule samples were collected from age-related cortical cataract patients over 50 years of age with LOCS III score of nuclear color ≥4 along with control subjects. DNAs were extracted and subjected to methylation microarray for the identification of methylated genes employing the high-throughput sequencing approach. RESULTS: Compared with the control group, 843 sites were found methylated, including 802 hypermethylation sites with 542 corresponding genes, 41 demethylation sites with 29 corresponding sites. COL4 A1, GJA3, SIPA1 L3 were confirmed by mass spectrometry, the results were consistent with high-throughput sequencing. CONCLUSION: DNA methylation microarrays is an efficient way for screening the aberrantly methylated genes. In this study, we are able to screen a few age-related cataract genes such as COL4 A1, GJA3, and SIPA1 L3 for their aberrant methylation patterns in cataract patients however further work is warranted to understand the significance of these findings.展开更多
Age-related cataract (ARC) is the most common cause of visual impairment and blindness worldwide. A previous study reported that genetic factors could explain approximately 50% of the heritability of cataract. Howev...Age-related cataract (ARC) is the most common cause of visual impairment and blindness worldwide. A previous study reported that genetic factors could explain approximately 50% of the heritability of cataract. However, a genetic predisposition to ARC and the contributing factors have not yet been elucidated in the Korean population. In this study, we assessed the influence of genetic polymorphisms on the risk of ARC in Koreans, including 156 cataract cases and 138 healthy adults. We conducted an exome-wide association study using Illumina Human Exome-12v1.2 platform to screen 244,770 single nucleotide polymorphisms (SNPs). No SNPs reached exome-wide significance level of association (P 〈 l x 10 6). B3GNT4 rs7136356 showed the most significant association with ARC (P = 6.54x 10 5). Two loci (MUC16 and P2RY2) among the top 20 ARC-associated SNPs were recognized as probably linked to cata- ractogenesis. Functions of these genes were potentially related to regulating dehydration or homeostasis of the eyes, and showed a potential association with dry eye disease. This finding suggests that mucin- and dry eye disease-related genes may play a significant role in cataractogenesis. Our study provides insight into the genetic predisposition of ARC in Koreans. Additional studies with larger sample sizes are required to confirm the results of this study.展开更多
AIM: To investigate the expression differences of transforming growth factor-β2(TGF-β2), basic fibroblast growth factor(b FGF) and intercellular cell-adhesion molecule-1(ICAM-1) in lens epithelial cells(LECs...AIM: To investigate the expression differences of transforming growth factor-β2(TGF-β2), basic fibroblast growth factor(b FGF) and intercellular cell-adhesion molecule-1(ICAM-1) in lens epithelial cells(LECs) of complicated cataract with silicone oil tamponade and agerelated cataract. METHODS: Totally 150 eyes of 150 patients(aged 35 to 77y) were investigated, including 75 patients with complicated cataract after silicone oil tamponade and 75 patients with age-related cataract. The central piece of anterior capsules was collected during cataract surgery. TGF-β2, b FGF and ICAM-1 were detected in the 60 specimens of the two groups by immunohistochemistry. The expression levels of the three kinds of messenger ribonucleic acid(m RNA) were determined by real-time quantitative reverse transcriptionpolymerase chain reaction in the 90 specimens of the two groups.RESULTS: TGF-β2 was detected in the cytomembrane and cytoplasm of the LECs and b FGF was detected in the nucleus. ICAM-1 was positive in the cytomembrane of the LECs and the distribution of positive cells was uneven. The m RNA genes expression of the TGF-β2, b FGF and ICAM-1 was significant differences between the two groups and markedly increased in complicated cataract group(P〈0.05).CONCLUSION: The up-regulated TGF-β2, b FGF and ICAM-1 maybe associate with the occurrence and development of complicated cataract with silicone oil tamponade.展开更多
AIM: To assess the level of glutathione, thioltransferase, and argpyrimidine in nuclear and cortical cataractous lenses as well as in the clear lenses in the north Indian population.METHODS: Human cataractous lenses...AIM: To assess the level of glutathione, thioltransferase, and argpyrimidine in nuclear and cortical cataractous lenses as well as in the clear lenses in the north Indian population.METHODS: Human cataractous lenses were collected from the patients who underwent extracapsular cataract extraction surgery; clear lenses were collected from the freshly donated eye bank eyes. Antioxidant molecules such as glutathione and thioltransferase enzyme activity were measured; simultaneously in these lenses a blue fluorophore argpyrimidine, an advanced glycation end(AGE) product level was assessed using high performance liquid chromatography(HPLC).RESULTS: The protein concentration was found to be present at higher levels in the control lenses compared to cataract lenses. A significant decrease in the glutathione level was observed in the nuclear cataractous lenses compared to cortical cataractous(P=0.004) and clear lenses(P≤0.005), but no significant change in the level of antioxidant enzyme thioltransferase was observed. Further, argpyrimidine a blue fluorophore(AGE) was found to be significantly higher in the nuclear cataract(P=0.013) compared to cortical cataract lenses.CONCLUSION: Antioxidants such as glutathione significantly decrease in age-related nuclear and cortical cataract and an AGE, argpyrimidine are present at significantly higher levels in nuclear cataract.展开更多
Background Contrast sensitivity (CS) testing can detect differences in functional vision and is highly correlated with visual performance. This study was designed to investigate the association between CS and the gr...Background Contrast sensitivity (CS) testing can detect differences in functional vision and is highly correlated with visual performance. This study was designed to investigate the association between CS and the grading score using the lens opacities classification system (LOCS) III as well as the association between CS and visual acuity (VA) in nuclear or cortical age-related cataract (ARC) patients. Methods A total of 270 eyes with ARC and 30 control eyes were divided into nuclear opacity (NO), nuclear color (NC), cortical cataract (C) based on LOCS II1. The CS values measured at all spatial frequencies under photopic and glare conditions that resulted in contrast sensitivity function (CSF) were evaluated, and LogMAR VA was tested with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The correlation between CSF and LOCS III grading scores, and between CSF and LogMAR VA were analyzed. Results Compared to the controls, CSF of the nuclear or cortical ARC significantly declined. There are significant correlation between CSF and LogMAR VA, and between CSF and LOCS III grading scores. Compared to the VA, a stronger correlation existed between CSF and LOCS III grading score than that of LogMAR VA and LOCS III grading score. CS at some spatial frequencies is significantly influenced with LOCS III grading score. Conclusions CSF significantly declined with the increasing ARC grading scores. Comparing to VA, CSF reflected the severity of cataract more comprehensively. CS at low spatial frequency is significantly influenced by ARC. Therefore, CS is more precise than VA in assessing the visual function of ARC patients.展开更多
Background:The aim of the study was to compare the dynamic defocus curve on patients post-implantation of the extended depth-of-focus(EDOF)and monofocal intraocular lens(IOL).Methods:A total of 62 age-related cataract...Background:The aim of the study was to compare the dynamic defocus curve on patients post-implantation of the extended depth-of-focus(EDOF)and monofocal intraocular lens(IOL).Methods:A total of 62 age-related cataract patients receiving phacoemulsification with implantation of TECNIS Symfony(ZXRoO)or monofocal IOLs were enrolled.The binocular static and dynamic defocus curves with corrected distance visual acuity were evaluated at one month postoperatively.Results:The ZXR00 group achieved signifcantly better intermediate(P=0.044)and near(P=0.017)visual acuity(VA)than the monofocal group.Two groups had similar uncorrected and corrected distance VA(P>0.05,respectively).The dynamic defocus curve revealed a smoother decline from 0.0 D to-2.0 D in the ZXRo0 group.Defocused dynamic VA in the ZXR00 group was significantly better(P<0.05)except at 0.0 D(P=0.724)and-0.5 D(P=0.176).The area under the curve(P=0.002)and corrected dynamic vision accommodation(P=0.001)derived from the dynamic defocus curves were better in the ZxRoo group.A positive correlation was observed between defocused dynamic and static VA in both groups(P<0.001).Multiple linear regression analysis indicated that defocused static VA and cor-rected dynamic vision accommodation were significant influential factors for the defocused dynamic VA from-1.0 D to-3.0 D(P<0.05).Conclusions:The EDOF IOL provided similar distant vision,better intermediate and near vision,and a better overall dynamic defocus curve than the monofocal IOL.The dynamic defocus curve may be comprehensively applied to evaluate the all-distance dynamic visual performance post-cataract surgery.展开更多
基金Supported by the Shaanxi Provincial Department of Science and Technology Agency Project(No.2022SF-502)Xi’an Medical University Scientific Research Capacity Improvement Project(No.2022NLTS104)+2 种基金The Fifth Batch of Key Disciplines of Xi’an Medical University(No.medical technology12202306)Yunzhen Optometry Special Fund(No.2021HXZR10)Innovation and Entrepreneurship Training Program for College Students(No.S202211840043).
文摘AIM:To explore the DNA methylation of COL4A1 in ultraviolet-B(UVB)-induced age-related cataract(ARC)models in vitro and in vivo.METHODS:Human lens epithelium B3(HLEB3)cells and Sprague Dawley rats were exposure to UVB respectively.The MTT assay was utilized to evaluate cell proliferation.Flow cytometry was employed for analysis of cell apoptosis and cell cycle.COL4A1 expression in HLEB3 cells and anterior lens capsules were assessed using Western blot and reverse transcription-polymerase chain reaction(RTPCR).The localization of COL4A1 in HLEB3 cells was determined by immunofluorescence.The methylation status of CpG islands located in COL4A1 promoter was verified using bisulfite-sequencing PCR(BSP).DNMTs and TETs mRNA levels was examined by RT-PCR.RESULTS:UVB exposure decreased HLEB3 cells proliferation,while increased the apoptosis rate and cells were arrested in G0/G1 phase.COL4A1 expression was markedly inhibited in UVB treated cells compared to the controls.Hypermethylation status was detected in the CpG islands within COL4A1 promoter in HLEB3 cells subjected to UVB exposure.Expressions of DNMTs including DNMT1/2/3 were elevated in UVB treated HLEB3 cells compared to that in the controls,while expressions of TETs including TET1/2/3 showed the opposite trend.Results from the UVB treated rat model further confirmed the decreased expression of COL4A1,hypermethylation status of the CpG islands at promoter of COL4A1 and abnormal expression of DNMT1/2/3 and TET1/2/in UVB exposure group.CONCLUSION:DNA hypermethylation of COL4A1 promoter CpG islands is correlated with decreased COL4A1 expression in UVB induced HLEB3 cells and anterior lens capsules of rats.
基金Supported by National Natural Science Foundation of China,No.32200545The GDPH Supporting Fund for Talent Program,No.KJ012020633 and KJ012019530Science and Technology Research Project of Guangdong Provincial Hospital of Chinese Medicine,No.YN2022GK04。
文摘BACKGROUND The importance of age on the development of ocular conditions has been reported by numerous studies.Diabetes may have different associations with different stages of ocular conditions,and the duration of diabetes may affect the development of diabetic eye disease.While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality,whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored.It is unclear which types of diabetes are more predictive of ocular conditions.AIM To examine associations between the age of diabetes diagnosis and the incidence of cataract,glaucoma,age-related macular degeneration(AMD),and vision acuity.METHODS Our analysis was using the UK Biobank.The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis,and 6689 diabetic participants and 13378 controls for vision analysis.Ocular diseases were identified using inpatient records until January 2021.Vision acuity was assessed using a chart.RESULTS During a median follow-up of 11.0 years,3874,665,and 616 new cases of cataract,glaucoma,and AMD,respectively,were identified.A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age.Individuals with type 2 diabetes(T2D)diagnosed at<45 years[HR(95%CI):2.71(1.49-4.93)],45-49 years[2.57(1.17-5.65)],50-54 years[1.85(1.13-3.04)],or 50-59 years of age[1.53(1.00-2.34)]had a higher risk of AMD independent of glycated haemoglobin.T2D diagnosed<45 years[HR(95%CI):2.18(1.71-2.79)],45-49 years[1.54(1.19-2.01)],50-54 years[1.60(1.31-1.96)],or 55-59 years of age[1.21(1.02-1.43)]was associated with an increased cataract risk.T2D diagnosed<45 years of age only was associated with an increased risk of glaucoma[HR(95%CI):1.76(1.00-3.12)].HRs(95%CIs)for AMD,cataract,and glaucoma associated with type 1 diabetes(T1D)were 4.12(1.99-8.53),2.95(2.17-4.02),and 2.40(1.09-5.31),respectively.In multivariable-adjusted analysis,individuals with T2D diagnosed<45 years of age[β95%CI:0.025(0.009,0.040)]had a larger increase in LogMAR.Theβ(95%CI)for LogMAR associated with T1D was 0.044(0.014,0.073).CONCLUSION The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.
基金Supported by Supporting Fund Project of Shaanxi Provincial Department of Science and Technology Agency Project(No.2022SF-502)Special Scientific Research Program of Education Department of Shaanxi Provincial Government(No.21JK0891)+1 种基金Young Talent Lifting Project of Xi’an Science and Technology Association(No.095920221365)Innovation and Entrepreneurship Training Program for College students of Xi’an Medical University(No.121521113)。
文摘AIM:To evaluate the regulation of the aberrant expression of collagen typeⅣalpha 1 chain(COL4A1)in the development of age-related cataract(ARC).METHODS:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and Western blot analysis were employed to evaluate the expression of COL4A1 in ARC patients and healthy controls.The proliferation,apoptosis,cell cycle and epithelial-mesenchymal transition(EMT)of human lens epithelial cell(HLE-B3)were further analyzed under the condition of COL4A1 gene silence.Alteration of gene expression at mRNA level after knockdown COL4A1 were also evaluated by qRT-PCR on HLE-B3 cells.RESULTS:The aberrant expression of COL4A1 was identified a clinically associated with the ARC.Silencing of COL4A1 promoted the apoptosis and inhibited the proliferation of HLE-B3 by blocking the cell cycle.Moreover,COL4A1 gene silence didn’t affect the cytoskeleton of HLE-B3 but down-regulated the Collagen typeⅣAlpha 2 Chain(COL4A2),paired box 6(PAX6),procollagen-lysine 2-oxoglutarate 5-dioxygenases 1(PLOD1)and procollagenlysine 2-oxoglutarate 5-dioxygenases 2(PLOD2)expression levels in HLE-B3 cells.Silencing the COL4A1 gene induced EMT of the HLE-B3 cells by promoting the transforming growth factor beta(TGF-β)expression.CONCLUSION:Silencing of COL4A1 induces S-phase arrest,also inhibits the proliferation and enhance HLE-B3 apoptosis and EMT,and down-regulates the expression of COL4A2,PAX6,PLOD1 and PLOD2.Thus,the expression alteration of COL4A1 may play a critical role in the pathogenesis of ARC.
基金This work was supported by the Nature Science Foundation of China(81470618)the Scientific Research Foundation of First Affiliated Hospital of Harbin Medical University(2017B013).
文摘Objective:Age-relate cataract(ARC)is a disease of the eyes with no effective drugs to prevent or treat patients.The aim of the present study is to determine whether histone H3,αA-crystallin(CRYAA),β-galactosidase(GLB1),and p53 are involved in the pathogenesis of ARC.Methods:A total of 99 anterior lens capsules(ALCs)of patients with ARC of various nuclear grades,ultraviolet models of ALCs,and two human lens epithelial cell lines(FHL-124 and SRA01/04)were used,and the expression of histone H3,CRYAA,GLB1,and p53 were detected by immunoblotting and reverse transcription and real time-quantitative polymerase chain reaction.The association between CRYAA with histone H3,GLB1,and p53 was assessed in FHL-124 and SRA01/04 cells following CRYAA overexpression.Results:Histone H3 and p53 in ALCs of patients with ARC were up-regulated in a grade-dependent manner,and the expression of CRYAA showed a positive association with histone H3,p53,and GLB1.In UV models of ALCs and human lens epithelial cell lines,the expression levels of histone H3,cell apoptosis factors(Bax/Bcl-2,cleaved caspase-3),and inflammation factors(interleukin-6,tumor necrosis factor-α)were all up-regulated.Furthermore,transfection of CRYAA in FHL-124 cells induced overexpression of histone H3.Conclusion:CRYAA-mediated upregulation of histone H3 may be involved in the pathogenesis of ARC.p53 may also have a role in ARC development,but not via the CRYAA-histone H3 axis.The results of the present study may assist in improving our understanding of the pathogenesis of ARC and in identifying potential targets for treatment.
基金Science and Technology Planning Project,Liaoning Province Education Administration,China(No.2008424)
文摘AIM: To determine the association between cigarettes smoking, body mass index (BMI) and the risk of age-related cataract (ARC) in middle-aged and elderly men in Northeast China. METHODS: A hospital-based case control study was conducted. Cases (n =362) were men who had surgically treated ARC, 45-85 years old; controls frequency-matched (n=362) were men who had been admitted to the same hospital as cases for other diseases not related with eye diseases. Cases and controls were matched with 1:1. The cases and controls were interviewed during their hospital stay, using a structured interviewer-administrated questionnaire that included information on sociodemographic characteristics, socioeconomic, lifestyle habits (tobacco smoking and alcohol consumption, etc.), anthropometric measures, personal medical history, and family history of ARC in first-degree relatives, and simultaneously BMI was calculated. The odds ratios (OR) and 95% confidence intervals (CI) of ARC were estimated using multiple logistic regression models. RESULTS: After adjusting for age and multiple potential confounders, higher BMI was associated with an increased risk of ARC. Cigarette smoking, years smoking or moderate cigarette smoking (1-29 cigarettes per day) had no relation with the risk of ARC (P>0.05), although patients smoking >= 30 cigarettes per day had an elevated risk of ARC as compared with the non-smokers (OR=1.55, 95% CI; 1.16-2.85, P=0.026). Higher BMI was associated with an increased risk of ARC. Both overweight and obesity was associated with an obviously increased risk for surgically ARC (OR=1.55, 95% CI:1.02-1.98, P=0.015 and OR=1.71, 95% CI:1.32-2.39, P=0.013 respectively) compared to normal BMI. Then participants were grouped into quartiles of BMI (Q1 to Q4), compared to controls in the lowest quartile, the ORfor cases in the highest quartile of BMI was 1.54 (OR=1.54, 95% CI: 1.08-2.46, P=0.022). The results of univariate analysis showed cigarette smoking was not associated with ARC formation for men with lower or normal BMI (P >0.05). Compared to the non-smokers, for men of overweight or obesity, cigarette smoking was associated with a significantly increased risk for surgically ARC (OR=2.00, 95% CI: 1.49-6.65, P=0.003 and OR=1.66, 95% CI: 1.63-13.21, P=0.002 respectively). Similarly, smokers in the highest quartile of BMI had approximately 1.5 times the risk of ARC as non-smokers in the lowest quartile (OR =1.46, 95% CI: 1.06-5.29, P<0.001). Followed multivariate models revealed that the association had never changed. CONCLUSION: Current cigarette smoking is positively related to ARC only among those who smoking 30 or more cigarettes per day. For men who are both overweight and obesity, cigarette smoking is associated with a significantly increased risk for ARC.
基金Supported by the Institutional Project Funding(No.20184712).
文摘AIM:To investigate the prevalence and risk factors of age-related cataract(ARC),ARC surgery procedures,and postoperative vision results among adults over 50 years old in the Binhu District of Wuxi City,China.METHODS:Thirty basic sampling units were analyzed via a cluster random sampling method.Detailed medical histories were collected and eye examinations were performed.Cataract prevalence and surgical procedures were quantified.RESULTS:Among the 6150 participants,1421 cataract cases were diagnosed and prevalence was 23.1%.The prevalence of cortical,nuclear,and posterior subcapsular cataracts increased with age(P<0.001).Cataract prevalence was significantly higher among elderly,female,or illiterate individuals and people with hypertension,diabetes,and a history of smoking and drinking(all P<0.05).As participant age increased and education level decreased,the frequency of cataract blindness surgeries gradually decreased,but without statistical significance within groups(P>0.05).The odds ratio of cataract patients who had or did not have cataract surgery was 3.15(87/28)and the frequency of cataract blindness surgery was 75.7%(87/115).Poor visual outcomes was in 107 eyes(40.7%)after cataract surgery.Poor vision was mostly caused by uncorrected reflective errors(30.9%)and ocular comorbidities(41.1%).The prevalence of cataract surgery complications was 5.7%(15/263).Surgical complications and posterior capsular opacification were avoidable factors facilitating poor vision.CONCLUSION:ARC,especially in females and illiterateindividuals,presents a public health problem in this district.Poor visual outcomes after cataract surgery are frequent.High-quality cataract surgeries and treatment of ocular comorbidities are vital.
基金Science and Technology Planning Project,Liaoning Province Education Administration,China(No.2008-424)
文摘AIM:To examine the association between dietary macronutrient intake and the risk of age-related cataract(ARC)in middle-aged and elderly men.METHODS:A hospital-based case-control study was conducted from December 2009 to November 2011.Cases(n=360)were patients with cataract aged 45-85years old,and controls(n=360)were patients who had been admitted to the same hospital for diseases not related with cataract.All subjects were interviewed using a structured interviewer-administrated questionnaire that included information on socio-demographic characteristics,lifestyle habits and detailed medical history,simultaneously,the dietary intakes of nutrients were collected via a valid semi-quantitative food frequency questionnaire(FFQ).The odds ratios(OR)and corresponding 95%confidence intervals(CI)of three types of ARC were estimated using multiple logistic regression models.RESULTS:After adjusting for multiple potential confounders,total dietary intake of carbohydrate was positively associated with cortical cataract,compared to controls in the lowest quartile,and the OR for cases in the highest quartile of intake was 2.471(95%CI:1.348-6.043,P=0.027).Higher dietary intakes of protein were protective for posterior subcapsular cataract(PSC)(OR=0.528,95%CI:0.148-0.869,P=0.023).Dietary fat intake was not associated with any type of cataract,however,participants in the highest quartile of polyunsaturated fatty acids intake had 2.7 times the risk of nuclear cataract as did those in the lowest quartile(OR=2.742,95%CI:1.790-4.200,P=0.033).CONCLUSION:A high intake of carbohydrate and polyunsaturated fatty acid may increase the odds of cortical and nuclear cataract,respectively,whereas high intake of protein,especially animal protein,may protect against PSC cataract.It is possible that dietary changes of target population may reduce the risk of ARC.
文摘AIM: To investigate the effects and mechanism of miR-211 in mediating the antioxidant function of lens epithelial cells affected by age-related cataracts. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect miR-211 expression in the anterior lens capsules of healthy people, the anterior lens capsules of patients with age-related cataracts, and human epithelial cell line (SRA01/04) cells exposed to oxidative stress. A 2', 7'-dichloro-fluorescein diacetate (DCFH-DA) probe was used to measure the levels of endogenous reactive oxygen species (ROS) in human lens epithelial cells (hLECs) exposed to 400 pmol/L H2O2 for lh. SRA01/04 cells were transfected with either miR-211 mimics, mimic controls, miR-211 inhibitors or inhibitor controls. After 72h, these cells were exposed to 400 IJmollL H2O2 for lh, then p53 and Bax mRNA expression were measured using RT-qPCR. p53 and Bax protein expression were also measured by Western blotting analysis. Finally, cell viability was assessed using an MTS assay. RESULTS: Compared to the control group, expression of miR-211 in the anterior lens capsules of age-related cataract patients and in SRA01/04 cells exposed to oxidative stress was significantly increased (P〈0.001). Levels of endogenous ROS were significantly elevated in hLECs exposed to oxidative stress (P〈0.001). Compared to the mimic control group, the hLECs in the miR-211 mimic group expressed significantly higher levels of p53 and Bax mRNA and protein while cell viability was significantly reduced (P〈0.001). Conversely, p53 and Bax mRNA and protein expression were significantly reduced in the miR-211 inhibitor group as compared to the control group, while the cells in this group had much higher levels of call viability (P〈0.001). CONCLUSION: miR-211 is upregulatsd in the anterior lens capsules of age-related cataract patients, miR-211 decreased the antioxidative stress capacity of lens epithelial cells by upregulating p53 and Bax, while inhibiting cell proliferation and repair. This finding suggests that miR-211 may play a key role in the development of age-related cataracts.
基金Supported by National Natural Science Foundation of China(No.81371000 No.81670834+4 种基金 No.81800807 No.81800869)the Natural Science Foundation of Zhejiang Province(No.LY17H090004)the Zhejiang Traditional Chinese Medicine Project(No.2013ZA080)the Fundamental Research Funds for the Central Universities(No.2018FZA7007)
文摘AIM: To determine the association of gap junction protein alpha 3(GJA3) gene tag single-nucleotide polymorphisms(SNPs) with susceptibility to age-related cataract(ARC).METHODS: In total, 486 ARC patients were matched with 500 healthy controls. All the participants underwent complete ophthalmic examinations. Haplotype-tagging SNPs of GJA3 gene were selected from the HapMap Beijing Han Chinese population. Genomic DNA was extracted from the peripheral blood leukocytes of all the subjects.Under three different genetic models: dominant, recessive,and additive, the association between SNPs and ARC was examined. After adjusting for age and sex, the genetic effects of the GJA3 SNPs were evaluated with logistic regression analysis.RESULTS: Four tag GJA3 SNPs(rs6490519, rs9506430,rs9509053, and rs9552089) were included in the present study. None of the SNPs showed a significant relationship with an altered risk of total ARC under the dominant,recessive, or additive models. In the subgroup analysis,rs9506430 had a significant effect on the formation of a posterior subcapsular cataract(P=0.002, OR: 0.227, 95%CI:0.088-0.590) under the recessive model.CONCLUSION: Our study indicates that GJA3 variants may influence the development of posterior subcapsular cataracts. Further studies need to be designed to confirm this possibility.
基金Supported by the National Natural Science Foundation of China(No.81473059)the Natural Science Foundation of Shaanxi Province of China(No.2017JM8041)the China Postdoctoral Science Special Foundation(No.2015T81036)。
文摘AIM: To summarize quantitatively the prospective association between physical activity and age-related cataract(ARC) risk.METHODS: Pub Med, Embase, Web of Science, and Cochrane Library were systematically searched for all relevant follow up studies until July 2019. Multivariableadjusted relative risks(RRs) and corresponding 95% confidence intervals(CIs) from individual studies were used to calculate the overall summary estimates. The doseresponse relationship was assessed using generalized least-squares trend estimation.RESULTS: Six prospective cohort studies, involving 19 173 cases in 6.2-12.1 y follow up of 171 620 participants, were included in the analysis. Increased physical activity was significantly associated with reduced risk of ARC by 10%(RR: 0.90;95%CI: 0.81, 0.99, P=0.04). Stratified analysis by assessment method for physical activity suggest that studies using metabolic equivalent(MET) per day tended to report a slightly stronger association with ARC(RR: 0.85;95%CI: 0.81, 0.90, P<0.001) than studies which assessed activity by weekly activity(RR: 0.96;95%CI: 0.89, 1.03, P=0.24). Dose-response analysis indicated that the risk of ARC decreased by 2%(RR: 0.98;95%CI: 0.98, 0.99, P<0.001) for every 6 METs per day increase in activity.CONCLUSION: The findings from this Meta-analysis provide additional evidence that increased physical activity is inversely associated with ARC risk dose-responsively.
基金Supported by the National Natural Science Foundation of China(No.81670834,No.81970781,No.81800807,No.81800869)the Natural Science Foundation of Zhejiang Province(No.LY17H090004).
文摘AIM:To explore the susceptible association between the insulin-like growth factor-1 receptor(IGF1 R)single nucleotide polymorphism(SNP)and age-related cataract(ARC),and investigate the underlying mechanisms in human lens epithelium(HLE)cells.METHODS:Totally 1190 unrelated participants,comprising 690 ARC patients and 500 healthy individuals in Han Chinese population were recruited and genotyped for target SNP.Theχ2-test was used to detect genotypic distribution between the patient and control groups and the logistic regression was performed to adjust the age and gender.Meanwhile,different biological experimental methods,such as cell counting kit 8(CCK-8)assay,flow cytometry,quantitative real time polymerase chain reaction(Q-PCR)and Western blot,were used to detect cell viability,cell cycle progression and apoptosis in HLE cells or IGF1 R knockdown HLE cells.RESULTS:The rs1546713 in IGF1 R gene was identified(P=0.046,OR:1.606,95%CI:1.245-2.071),which shown a significant relevance with ARC risk under the dominant model.The results demonstrated that IGF1 R knockdown inhibited cell proliferation by inducing cell cycle arrested at S phase and promoting apoptosis.Mechanistically,the cell cycle blocked at S phase was linked with the alterations of cyclin A,cyclin B,cyclin E and P21.The pro-apoptosis function of IGF1 R may related with stimulating the activation of Caspase-3 and altering the expression levels of apoptotic proteins,including Bcl-2,Bax and Caspase-3.CONCLUSION:This study first report that IGF1 R polymorphisms may affect susceptibility to ARCs in Han Chinese population and provide new clues to understand the pathogenic mechanism of ARCs.Notably,IGF1 R is likely a potential target for ARC prevention and treatment.
基金Supported by the Shaanxi Provincial Department of Science and Technology Agency Project(No.2017SF-288)
文摘AIM: To analyze and screen the methylation status of whole-genome in age-related cataract samples. METHODS: Anterior lens capsule samples were collected from age-related cortical cataract patients over 50 years of age with LOCS III score of nuclear color ≥4 along with control subjects. DNAs were extracted and subjected to methylation microarray for the identification of methylated genes employing the high-throughput sequencing approach. RESULTS: Compared with the control group, 843 sites were found methylated, including 802 hypermethylation sites with 542 corresponding genes, 41 demethylation sites with 29 corresponding sites. COL4 A1, GJA3, SIPA1 L3 were confirmed by mass spectrometry, the results were consistent with high-throughput sequencing. CONCLUSION: DNA methylation microarrays is an efficient way for screening the aberrantly methylated genes. In this study, we are able to screen a few age-related cataract genes such as COL4 A1, GJA3, and SIPA1 L3 for their aberrant methylation patterns in cataract patients however further work is warranted to understand the significance of these findings.
文摘Age-related cataract (ARC) is the most common cause of visual impairment and blindness worldwide. A previous study reported that genetic factors could explain approximately 50% of the heritability of cataract. However, a genetic predisposition to ARC and the contributing factors have not yet been elucidated in the Korean population. In this study, we assessed the influence of genetic polymorphisms on the risk of ARC in Koreans, including 156 cataract cases and 138 healthy adults. We conducted an exome-wide association study using Illumina Human Exome-12v1.2 platform to screen 244,770 single nucleotide polymorphisms (SNPs). No SNPs reached exome-wide significance level of association (P 〈 l x 10 6). B3GNT4 rs7136356 showed the most significant association with ARC (P = 6.54x 10 5). Two loci (MUC16 and P2RY2) among the top 20 ARC-associated SNPs were recognized as probably linked to cata- ractogenesis. Functions of these genes were potentially related to regulating dehydration or homeostasis of the eyes, and showed a potential association with dry eye disease. This finding suggests that mucin- and dry eye disease-related genes may play a significant role in cataractogenesis. Our study provides insight into the genetic predisposition of ARC in Koreans. Additional studies with larger sample sizes are required to confirm the results of this study.
基金Supported by the Natural Science Foundation of Shaanxi Province(No.2012JM4023)
文摘AIM: To investigate the expression differences of transforming growth factor-β2(TGF-β2), basic fibroblast growth factor(b FGF) and intercellular cell-adhesion molecule-1(ICAM-1) in lens epithelial cells(LECs) of complicated cataract with silicone oil tamponade and agerelated cataract. METHODS: Totally 150 eyes of 150 patients(aged 35 to 77y) were investigated, including 75 patients with complicated cataract after silicone oil tamponade and 75 patients with age-related cataract. The central piece of anterior capsules was collected during cataract surgery. TGF-β2, b FGF and ICAM-1 were detected in the 60 specimens of the two groups by immunohistochemistry. The expression levels of the three kinds of messenger ribonucleic acid(m RNA) were determined by real-time quantitative reverse transcriptionpolymerase chain reaction in the 90 specimens of the two groups.RESULTS: TGF-β2 was detected in the cytomembrane and cytoplasm of the LECs and b FGF was detected in the nucleus. ICAM-1 was positive in the cytomembrane of the LECs and the distribution of positive cells was uneven. The m RNA genes expression of the TGF-β2, b FGF and ICAM-1 was significant differences between the two groups and markedly increased in complicated cataract group(P〈0.05).CONCLUSION: The up-regulated TGF-β2, b FGF and ICAM-1 maybe associate with the occurrence and development of complicated cataract with silicone oil tamponade.
文摘AIM: To assess the level of glutathione, thioltransferase, and argpyrimidine in nuclear and cortical cataractous lenses as well as in the clear lenses in the north Indian population.METHODS: Human cataractous lenses were collected from the patients who underwent extracapsular cataract extraction surgery; clear lenses were collected from the freshly donated eye bank eyes. Antioxidant molecules such as glutathione and thioltransferase enzyme activity were measured; simultaneously in these lenses a blue fluorophore argpyrimidine, an advanced glycation end(AGE) product level was assessed using high performance liquid chromatography(HPLC).RESULTS: The protein concentration was found to be present at higher levels in the control lenses compared to cataract lenses. A significant decrease in the glutathione level was observed in the nuclear cataractous lenses compared to cortical cataractous(P=0.004) and clear lenses(P≤0.005), but no significant change in the level of antioxidant enzyme thioltransferase was observed. Further, argpyrimidine a blue fluorophore(AGE) was found to be significantly higher in the nuclear cataract(P=0.013) compared to cortical cataract lenses.CONCLUSION: Antioxidants such as glutathione significantly decrease in age-related nuclear and cortical cataract and an AGE, argpyrimidine are present at significantly higher levels in nuclear cataract.
文摘Background Contrast sensitivity (CS) testing can detect differences in functional vision and is highly correlated with visual performance. This study was designed to investigate the association between CS and the grading score using the lens opacities classification system (LOCS) III as well as the association between CS and visual acuity (VA) in nuclear or cortical age-related cataract (ARC) patients. Methods A total of 270 eyes with ARC and 30 control eyes were divided into nuclear opacity (NO), nuclear color (NC), cortical cataract (C) based on LOCS II1. The CS values measured at all spatial frequencies under photopic and glare conditions that resulted in contrast sensitivity function (CSF) were evaluated, and LogMAR VA was tested with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The correlation between CSF and LOCS III grading scores, and between CSF and LogMAR VA were analyzed. Results Compared to the controls, CSF of the nuclear or cortical ARC significantly declined. There are significant correlation between CSF and LogMAR VA, and between CSF and LOCS III grading scores. Compared to the VA, a stronger correlation existed between CSF and LOCS III grading score than that of LogMAR VA and LOCS III grading score. CS at some spatial frequencies is significantly influenced with LOCS III grading score. Conclusions CSF significantly declined with the increasing ARC grading scores. Comparing to VA, CSF reflected the severity of cataract more comprehensively. CS at low spatial frequency is significantly influenced by ARC. Therefore, CS is more precise than VA in assessing the visual function of ARC patients.
基金This work was supported by Bejing Municipal Science and Technology Commission(Grant No.7202229)Peking University Medicine Fund of Fostering Young Scholars'Scientific&Technological Innovation(Grant No.BMU2022PYB022)。
文摘Background:The aim of the study was to compare the dynamic defocus curve on patients post-implantation of the extended depth-of-focus(EDOF)and monofocal intraocular lens(IOL).Methods:A total of 62 age-related cataract patients receiving phacoemulsification with implantation of TECNIS Symfony(ZXRoO)or monofocal IOLs were enrolled.The binocular static and dynamic defocus curves with corrected distance visual acuity were evaluated at one month postoperatively.Results:The ZXR00 group achieved signifcantly better intermediate(P=0.044)and near(P=0.017)visual acuity(VA)than the monofocal group.Two groups had similar uncorrected and corrected distance VA(P>0.05,respectively).The dynamic defocus curve revealed a smoother decline from 0.0 D to-2.0 D in the ZXRo0 group.Defocused dynamic VA in the ZXR00 group was significantly better(P<0.05)except at 0.0 D(P=0.724)and-0.5 D(P=0.176).The area under the curve(P=0.002)and corrected dynamic vision accommodation(P=0.001)derived from the dynamic defocus curves were better in the ZxRoo group.A positive correlation was observed between defocused dynamic and static VA in both groups(P<0.001).Multiple linear regression analysis indicated that defocused static VA and cor-rected dynamic vision accommodation were significant influential factors for the defocused dynamic VA from-1.0 D to-3.0 D(P<0.05).Conclusions:The EDOF IOL provided similar distant vision,better intermediate and near vision,and a better overall dynamic defocus curve than the monofocal IOL.The dynamic defocus curve may be comprehensively applied to evaluate the all-distance dynamic visual performance post-cataract surgery.