• 文章类型: Journal Article
    很少系统地探讨白内障风险归因负担的全球分布和趋势。指导制定针对性、精准性的白内障筛查和治疗策略,我们分析了已知危险因素导致的白内障疾病负担.
    这项研究利用了来自2019年全球疾病负担的详细白内障数据,我们分析了1990年至2019年的残疾调整寿命年(DALYs)e每个风险因素。此外,我们计算了研究期间估计的年度百分比变化(EAPC).
    结果显示,从1990年至2019年,可归因于颗粒物污染的e的全球年龄标准化DALYs,吸烟,高空腹血糖和高BMI呈稳定下降趋势(1990-2009:EAPC=-0.21[-0.57-0.14]);2000-2009:EAPC=-0.95[-1.01-0.89];2010-2019:EAPC=-1.41[-1.8-1.02]).在中低社会人口统计学指数(SDI)地区,年龄标准化的DALYs和由每种危险因素引起的死亡率最高(EAPC=-1.77[(-2.19--1.34)])。男性白内障的总体疾病负担低于女性。当单独分析白内障疾病负担的EAPC时,每个危险因素,我们发现颗粒物污染和吸烟导致的年龄标准化残疾调整寿命降低(PMP1990-2009:EAPC=-0.53[-0.9--0.16];2000-2009:EAPC=-1.39[-1.45--1.32];2010-2019:EAPC=-2.27[-2.75--1.79];吸烟2000-2009:EAPC=-1.51[-1.643],2009年至2019年:EAPC=-1.34[-1.68--1])),而高空腹血糖和高体重指数逐年增加(HFPG1990至1999:EAPC=1.27[0.89-1.65],2000年至2009年:EAPC=1.02[0.82-1.22],2010-2019:EAPC=0.44[0.19-0.68];HBMI1990-1999:EAPC=1.65[1.37-1.94],2000年至2009年:EAPC=1.56[1.43-1.68],2010-2019年:EAPC=1.47[1.18-1.77])。
    由环境颗粒物和吸烟引起的白内障负担正在增加,中低端SDI地区,迫切需要具体有效的措施。这项研究的结果表明,减少颗粒物污染,戒烟,控制血糖,降低BMI对减少白内障的发生有重要作用,尤其是老年人。
    UNASSIGNED: The global distribution and trends in the attributable burden of cataract risk have rarely been systematically explored. To guide the development of targeted and accurate cataract screening and treatment strategies, we analyzed the burden of cataract disease attributable to known risk factors.
    UNASSIGNED: This study utilized detailed cataract data from the Global Burden of Disease e 2019, and we analyzed disability-adjusted life years (DALYs) e each risk factor from 1990 to 2019. Additionally, we calculated estimated annual percentage changes (EAPCs) during the study period.
    UNASSIGNED: The results revealed that from 1990-2019, the global age-standardized DALYs of e attributable to particulate matter pollution, smoking, high fasting glucose plasma and high BMI showed steady downward trends (1990-2009: EAPC = -0.21 [-0.57 -0.14]); 2000-2009: EAPC = -0.95 [-1.01 -0.89]; 2010-2019: EAPC = -1.41 [-1.8 -1.02]). The age-standardized DALYs and mortality caused by each risk factor were highest in the low-middle sociodemographic index (SDI) region (EAPC = -1.77[(-2.19--1.34)]). The overall disease burden of cataracts is lower in males than in females. When analyzing the EAPCs of cataract disease burden for each risk factor individually, we found that the age-standardized disability-adjusted life years caused by particulate matter pollution and smoking decreased (PMP1990-2009: EAPC = -0.53 [-0.9--0.16]; 2000-2009: EAPC = -1.39 [-1.45--1.32]; 2010-2019: EAPC = -2.27 [-2.75--1.79]; smoking 2000 to 2009: EAPC = -1.51 [-1.6--1.43], 2009 to 2019: EAPC = -1.34 [-1.68--1])), while high fasting plasma glucose and high body mass index increased annually (HFPG1990 to 1999: EAPC = 1.27 [0.89-1.65], 2000 to 2009: EAPC = 1.02 [0.82-1.22], 2010-2019: EAPC = 0.44 [0.19-0.68]; HBMI 1990 to 1999: EAPC = 1.65 [1.37-1.94], 2000 to 2009: EAPC = 1.56 [1.43-1.68], 2010-2019: EAPC = 1.47 [1.18-1.77]).
    UNASSIGNED: The burden of cataracts caused by ambient particulate matter and smoking is increasing in low, low-middle SDI areas, and specific and effective measures are urgently needed. The results of this study suggest that reducing particulate matter pollution, quitting smoking, controlling blood glucose, and lowering BMI could play important roles in reducing the occurrence of cataracts, especially in older people.
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  • 文章类型: Journal Article
    (1)背景:本研究旨在评估无眼部病理的患者白内障手术后神经节细胞层厚度(GCLT)的变化以及黄斑囊样水肿的出现对GCLT和视力的影响。(2)方法:对174例具有单纯性白内障手术指征的患者进行评估。分析的变量是人口统计数据,最佳矫正视力(BCVA),白内障类型和OCT(光学相干断层扫描)测量中心黄斑厚度(CMT),术前和一天,囊肿和GCLT的存在,手术后1个月和3个月.(3)结果:无并发症白内障手术后视网膜GCLT的增加与BCVA之间存在相关性。微囊的存在减少了GCL的厚度,这与BCVA的损失显着相关。术后1个月出现黄斑囊样水肿也与术前CMT有关。手术后一个月,微囊肿患者的术前GCL有统计学意义的下降,但术前CMT有统计学意义的上升。(4)结论:非复杂性白内障术后视网膜GCLT与BCVA之间存在一定的相关性。微囊的存在显着降低了GCL的厚度,这与BCVA的损失显着相关。
    (1) Background: This research aimed to evaluate the changes in ganglion cell layer thickness (GCLT) after uncomplicated cataract surgery in patients without previous ocular pathology and the impact of the appearance of cystoid macular edema on the GCLT and visual acuity. (2) Methods: The evaluation of 174 patients was performed with the indication of uncomplicated cataract surgery. The variables analyzed were demographic data, best-corrected visual acuity (BCVA), cataract type and OCT (Optical Coherence Tomography) measurements of central macular thickness (CMT), and the presence of cysts and GCLT preoperatively and one day, one and three months after surgery. (3) Results: There was a relationship between the postoperative increase in retinal GCLT and BCVA after uncomplicated cataract surgery. The presence of microcysts reduced the thickness of the GCL, which is significantly related to the loss of BCVA. The appearance of cystoid macular edema one month after surgery was also related to the preoperative CMT. There was a statistically significant decrease in preoperative GCL but a statistically significant increase in preoperative CMT in patients with microcysts one-month post-surgery. (4) Conclusions: There is a relationship between postoperative retinal GCLT and BCVA after uncomplicated cataract surgery. The presence of microcysts significantly reduces the thickness of the GCL, which is significantly related to the loss of BCVA.
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  • 文章类型: Journal Article
    本研究旨在探讨角膜生物力学特性的影响,角膜滞后(CH),角膜阻力因子(CRF)对白内障术后散光的影响及其他因素的影响。40例患者的40只眼(13M/27F;中位年龄74岁)纳入本前瞻性研究,接受2.75mm切口白内障手术,并被跟踪了30天。在手术前的基线(V0)安排访视,第一(V1),第七(V2)术后第30天(V3)。用Statistica®14.0.1估计和分析的主要参数是CH,CRF,散光屈光度,和轴。白内障手术后,研究访视期间CH无显著变化(p=0.109).然而,在研究访视期间(根据方案组),CRF与基线相比有显著变化(p=0.002).在从V0到V1轻微但不显著的增加之后,事后分析发现平均CRF从V1到V2显著降低(p=0.049),从V2到V3没有实质性变化。根据事后分析,中位散光屈光度从V0到V1仅显著增加(p=0.001),并且在研究结束时略有降低,但没有显著降低,达到接近基线值.通过逐步回归分析获得的最终散光屈光度(R2=0.898)的主要预测因子是其在V0,V1和V2的值(p<0.001)。V1时的CRF略有差异,负参数估计为-0.098303(p=0.0623)。总之,使用2.75mm切口白内障手术,术前CH和CRF与术后散光之间没有相关性。然而,最终散光屈光度的主要预测指标是白内障手术前的基线值,第一,和术后第七天。
    This study aimed to investigate the impact of the cornea\'s biomechanical properties, corneal hysteresis (CH), and corneal resistance factor (CRF) on postoperative astigmatism after cataract surgery and determine the other factors that influence it. Forty eyes of 40 patients (13M/27F; the median age of 74) were included in this prospective study, underwent 2.75 mm incision cataract surgery, and were followed for 30 days. Visits were scheduled at baseline before surgery (V0), the 1st (V1), the 7th (V2), and the 30th (V3) postoperative days. The main parameters estimated and analyzed with Statistica® 14.0.1 were CH, CRF, astigmatism diopter, and axis. Following the cataract surgery, the CH did not significantly change during the study visits (p = 0.109). However, there was a significant change in the CRF from baseline during the study visits (per protocol set) (p = 0.002). After a slight but insignificant increase from V0 to V1, post hoc analysis found a significant decrease in the mean CRF from V1 to V2 (p = 0.049) with no substantial change from V2 to V3. According to the post hoc analysis, the median astigmatism diopter increased significantly only from V0 to V1 (p = 0.001) and slightly but not significantly decreased to the end of the study with the achievement of a near-baseline value. The main predictors for the final astigmatism diopter (R2 = 0.898) obtained by stepwise regression analysis were its values at V0, V1, and V2 (p < 0.001). The CRF at V1 was marginally significant, with a negative parameter estimate of -0.098303 (p = 0.0623). In conclusion, there was no correlation between preoperative CH and CRF and postoperative astigmatism using 2.75 mm incision cataract surgery. However, the final astigmatism diopter\'s main predictors were its baseline values before cataract surgery, the first, and the seventh postoperative days.
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  • 文章类型: Journal Article
    白内障超声乳化术是发达国家白内障手术的标准护理,患者对视觉结果有很高的期望。术后因阴性吞咽困难(ND)引起的不满意从罕见到非常常见;其病因尚不清楚,影响术后满意度。由于避免ND的最常用策略之一与人工晶状体(IOL)触觉取向有关,我们进行了一项前瞻性介入研究,纳入了197例接受标准超声乳化手术的患者.所有患者均植入一件式疏水丙烯酸人工晶状体;在一组中,触觉被放置在任何子午轴,除了下颞叶(IT)子午线,在另一组中,IOL在IT位置植入了触觉。在分析第1周和第1个月中IOL触觉的位置与ND的存在之间的相关性时,我们的结果显示组间没有统计学上的显着差异。此外,有或没有ND的患者之间的瞳孔直径无统计学差异。尽管一些研究声称触觉定向阻止了ND,我们发现触觉方向与ND发生率不相关,并且ND从第1天到第1个月降低。我们的结果支持先前关于ND随时间减少的发现,并且触觉定向不应被视为避免这种不必要现象的术中策略。
    Phacoemulsification is the standard of care in cataract surgery in the developed world, with patients having high expectations regarding visual results. Postoperative dissatisfaction due to negative dysphotopsia (ND) ranges from rare to very frequent; its etiology is unclear, and it affects postoperative satisfaction. Since one of the most frequently used strategies to avoid ND is related to intraocular lens (IOL) haptic orientation, we conducted a prospective interventional study that enrolled 197 patients who underwent standard phacoemulsification. All patients had a one-piece hydrophobic acrylic IOL implanted; in one group, the haptics were placed in any meridional axis except inferotemporal (IT) meridians, and in the other group, the IOL was implanted with the haptics in an IT position. Our results showed no statistically significant differences between groups when analyzing the correlation between the position of IOL haptics and the presence of ND in week one and month one. Also, pupillary diameter showed no statistically significant differences between patients with or without ND. Despite some studies claiming that haptic orientation prevents ND, we found that haptic orientation does not correlate with ND incidence and that ND decreases from day 1 to month 1. Our results support previous findings on the decrease in ND over time and that haptic orientation should not be considered an intraoperative strategy to avoid this unwanted phenomenon.
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  • 文章类型: Journal Article
    白内障的特征是眼睛的晶状体变得浑浊,干眼症(DED)是一种多因素疾病,其中泪膜的稳态丢失。由于这两种疾病的患病率随着年龄的增长而增加,在接受白内障手术的患者中,DED的患病率较高.近年来,白内障手术已经从视力恢复手术发展到屈光手术。为了获得良好的手术效果,在人工晶状体(IOL)屈光力计算中,有必要最大程度地减少术后屈光不正,这需要精确的术前角膜曲率测量。稳定的泪膜对于角膜曲率测量的准确性和再现性很重要,和DED可能有有害的影响。在这项研究中,对主要关注与该主题相关的发现的原始文章进行了评估。根据系统评价和荟萃分析(PRISMA)指南的首选报告项目进行系统评价。虽然适当的DED诊断没有在本综述评估的文章中提出,证实了DED的临床症状,特别是缩短泪膜破裂时间(TBUT),对IOL功率计算产生负面影响。这些临床症状的改善可能会减轻对这些计算的负面影响。
    Cataracts are characterized by the crystalline lens of the eye becoming cloudy, and dry eye disease (DED) is a multifactorial disease in which the homeostasis of the tear film is lost. As the prevalence of both diseases increases with age, there is a high prevalence of DED among patients who are candidates for cataract surgery. In recent years, cataract surgery has evolved from vision restoration surgery to refractive surgery. To achieve good surgical outcomes, it is necessary to minimize postoperative refractive error in intraocular lens (IOL) power calculation, which requires accurate preoperative keratometry measurements. A stable tear film is important for the accuracy and reproducibility of keratometry measurements, and DED may have a deleterious effect. In this study, original articles that focused primarily on findings related to this topic were evaluated. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Although appropriate DED diagnoses were not presented in the articles evaluated in this review, it was confirmed that the clinical signs of DED, particularly the shortening of the tear film break-up time (TBUT), negatively impact IOL power calculations. Improvement in these clinical signs might mitigate the negative effects on these calculations.
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  • 文章类型: Journal Article
    透明眼晶状体的浑浊,或白内障,是视力障碍的主要原因,需要用合成人工晶状体进行手术置换以有效恢复清晰视力。大多数情况下,白内障是随着年龄的增长而获得的多因素或复杂特征。白内障也可以作为经典的孟德尔特征遗传-通常具有早期或儿科发作-具有或不具有其他眼部和/或全身特征。自1990年代初以来,超过85个基因和基因座与遗传和/或年龄相关形式的白内障遗传相关。虽然许多这些潜在的基因-包括晶状体晶状体蛋白的基因,连接蛋白,和转录因子-概括晶状体发育和分化的特征,越来越多的不可预测的基因,包括那些参与细胞信号传导的,膜重塑,和自噬,已经出现-提供了关于晶状体稳态和衰老的新见解。这篇综述提供了在Cat-Map数据库中汇编的遗传性和年龄相关形式的白内障的基因发现的简要历史,并强调了潜在的基于基因的延迟治疗方法,反向,甚至预防白内障的形成,这可能有助于减少对白内障手术日益增长的需求。
    Clouding of the transparent eye lens, or cataract(s), is a leading cause of visual impairment that requires surgical replacement with a synthetic intraocular lens to effectively restore clear vision. Most frequently, cataract is acquired with aging as a multifactorial or complex trait. Cataract may also be inherited as a classic Mendelian trait-often with an early or pediatric onset-with or without other ocular and/or systemic features. Since the early 1990s, over 85 genes and loci have been genetically associated with inherited and/or age-related forms of cataract. While many of these underlying genes-including those for lens crystallins, connexins, and transcription factors-recapitulate signature features of lens development and differentiation, an increasing cohort of unpredicted genes, including those involved in cell-signaling, membrane remodeling, and autophagy, has emerged-providing new insights regarding lens homeostasis and aging. This review provides a brief history of gene discovery for inherited and age-related forms of cataract compiled in the Cat-Map database and highlights potential gene-based therapeutic approaches to delay, reverse, or even prevent cataract formation that may help to reduce the increasing demand for cataract surgery.
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  • 文章类型: Case Reports
    MAF基因编码转录因子,其中致病变体与孤立性和综合征性先天性白内障有关。我们的目的是回顾与非综合征性先天性白内障相关的C端DNA结合域中的MAF变体,并描述一个新的患者,引起疾病的从头错义变异。对C末端MAF变体及其相关的先天性白内障和眼科发现的发表报告进行了综述。我们介绍的患者和他的亲生父母通过靶向基因小组进行基因检测,然后进行基于三重的全外显子组测序。一名有双侧核性和皮质性白内障病史的4岁患者被发现患有一种新的,MAF中可能的致病性从头变异,NM_005360.5:c.922A>G(p。Lys308Glu)。未发现综合征或眼前节异常。我们报告了新的错觉变体,c.922A>G(p。Lys308Glu),在MAF的C端DNA结合域中,被分类为可能致病并与非综合征型双侧先天性白内障有关。
    The MAF gene encodes a transcription factor in which pathogenic variants have been associated with both isolated and syndromic congenital cataracts. We aim to review the MAF variants in the C-terminal DNA-binding domain associated with non-syndromic congenital cataracts and describe a patient with a novel, disease-causing de novo missense variant. Published reports of C-terminal MAF variants and their associated congenital cataracts and ophthalmic findings were reviewed. The patient we present and his biological parents had genetic testing via a targeted gene panel followed by trio-based whole exome sequencing. A 4-year-old patient with a history of bilateral nuclear and cortical cataracts was found to have a novel, likely pathogenic de novo variant in MAF, NM_005360.5:c.922A>G (p.Lys308Glu). No syndromic findings or anterior segment abnormalities were identified. We report the novel missense variant, c.922A>G (p.Lys308Glu), in the C-terminal DNA-binding domain of MAF classified as likely pathogenic and associated with non-syndromic bilateral congenital cataracts.
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  • 文章类型: Journal Article
    本研究旨在评估尼古丁替代疗法(NRT)与伐尼克林,未经治疗的吸烟有发展为眼部疾病的风险。我们采用了新用户设计,以调查NRT使用与台湾国民健康保险计划的眼疾发病率之间的关联。这项研究包括8416名接受NRT的吸烟者和8416名没有接受NRT的吸烟者(对照组),使用2007年至2018年的倾向评分进行匹配。经相关因素调整后,多变量Cox回归分析显示,与未经治疗的吸烟者相比,使用NRT与黄斑变性的风险显着降低相关(风险比[HR]:0.34;95%置信区间[CI]:0.13-0.87,P=0.024)。当按剂量分层时,与未治疗相比,短期使用NRT(8~28个确定的日剂量)与青光眼风险显著降低(HR:0.35;95%CI:0.16~0.80,P=0.012)和白内障风险降低趋势相关(HR:0.60;95%CI:0.36~1.01,P=0.053).然而,这些关联在长期使用NRT时未观察到.这项真实世界观测研究的结果表明,NRT使用,特别是短期使用,与没有戒烟治疗相比,某些眼部疾病的风险较低。长期使用NRT并未显示出相同的益处。因此,短期NRT可能是降低试图戒烟的吸烟者眼部疾病风险的有益治疗策略.然而,需要进一步的证据来验证这些发现并确定NRT使用的最佳持续时间.
    This study aims to assess the association between nicotine replacement therapy (NRT), varenicline, and untreated smoking with the risk of developing eye disorders. We employed a new-user design to investigate the association between NRT use and the incidence of eye disorders by the Taiwan National Health Insurance program. This study included 8416 smokers who received NRT and 8416 smokers who did not receive NRT (control group) matched using propensity scores between 2007 and 2018. After adjustment for relevant factors, a multivariable Cox regression analysis revealed that compared with untreated smokers, NRT use was associated with a significantly reduced risk of macular degeneration (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.13-0.87, P = 0.024). When stratified by dose, short-term NRT use (8-28 defined daily doses) was associated with significantly lower risk of glaucoma (HR: 0.35; 95% CI: 0.16-0.80, P = 0.012) and a trend toward reduced risk of cataract (HR: 0.60; 95% CI: 0.36-1.01, P = 0.053) compared to no treatment. However, these associations were not observed with long-term NRT use. The results of this real-world observational study indicate that NRT use, particularly short-term use, was associated with a lower risk of certain eye disorders compared to no treatment for smoking cessation. Long-term NRT use did not demonstrate the same benefits. Thus, short-term NRT may be a beneficial treatment strategy for reducing the risk of eye disorders in smokers attempting to quit. However, further evidence is required to verify these findings and determine the optimal duration of NRT use.
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  • 文章类型: Case Reports
    作者介绍了一例38岁的Alport综合征患者。该患者有该疾病的几种眼部症状,自15岁以来一直接受与Alport综合征有关的全身性问题的治疗。在那个年龄,患者还接受了肾脏移植以治疗肾功能不全。迄今为止,他仍然使用免疫抑制剂和抗高血压药。此外,病人患有感知性耳聋。患者于2021年访问了我们的诊所,要求解决他的高屈光不正,屈光度如此之高,以至于无法将其放置在眼镜中。患者的最佳矫正视力为0.6,右眼为-8.0sph/-4.0cyl/ax15,左眼为0.7partim,左眼为-8.0sph/-4.0cyl/ax155。右眼自动折射仪值为-6.25sph/-6.75cyl/ax17,左眼为-6.75sph/-6.5cyl/ax155。在眼科检查中,我们发现了许多典型的Alport综合征的眼部表现。角膜上有混浊,作为角膜糜烂的残留物,在以下检查中,我们还发现了新出现的角膜糜烂。随后,我们发现了前肠锥和早期白内障。在执行OCT时,典型的颞叶黄斑萎缩是明显的。人工散瞳的眼底检查仅显示出斑点视网膜病变的最小表现。由于临床表现,我们决定进行白内障手术并在双眼中植入单焦点复曲面人工晶状体。手术期间没有并发症,然而,外科医生登记的晶状体囊的非标准结构。胶囊更脆弱,进行撕囊手术要复杂得多。手术一周后,更高的圆柱体屈光度仍然存在。手术后一个月明显减少了较高的屈光度。第一次手术和第二次手术之间的时间间隔为一个月。患者对结果非常满意,未矫正视力提高了四行以上。手术后,患者需要近距离和远距离的低屈光度。就这个病人而言,在成年期检测和治疗眼部表现。然而,在肾功能衰竭之前早期发现年轻患者的Alport综合征的眼部症状可能导致及时开始治疗并延迟可能的肾移植。如果怀疑Alport综合征,建议将患者送往儿科医生,在更大的年龄去找内科专家,作进一步检查。
    The authors present a case of a thirty-eight-year-old patient with Alport syndrome. The patient had several ocular symptoms of the disease and has been treated for systemic problems in connection with Alport syndrome since he was fifteen years old. At that age the patient also underwent a kidney transplant in order to deal with renal insufficiency. To date, he still uses immunosuppressants and antihypertensives. Furthermore, the patient suffers from perceptive deafness. The patient visited our clinic in 2021 with a request to solve his high refractive error, in which the diopters were so high that it was not possible to place them in spectacles. The patient\'s best corrected visual acuity was 0.6 with -8.0sph/-4.0cyl/ax15 in the right eye and 0.7partim with -8.0sph/-4.0cyl/ax155 in the left eye. The autorefractometer values were -6.25sph/-6.75cyl/ax17 in the right eye and -6.75sph/-6.5cyl/ax155 in the left eye. During the eye examination we found a number of ocular manifestations that are typical of Alport syndrome. On the cornea there were opacities as a residue of corneal erosions, and at one of the following check-ups we also found a newly developed corneal erosion. Subsequently, we found an anterior lenticonus and incipient cataract. Upon performing OCT, a typical temporal macular atrophy was evident. Fundus examination in artificial mydriasis showed just a minimal manifestation of fleck retinopathy. Due to the clinical manifestation we decided to perform cataract surgery and implant a monofocal toric intraocular lens in both eyes. There were no complications during the operations, however the surgeon registered a non-standard structure of the lens capsule. The capsule was more fragile, and performing capsulorhexis was much more complicated. A week after the surgery, higher cylinder diopters were still present. A decrease of the higher diopters was noticeable one month after surgery. The time interval between the first operation and the second operation was one month. The patient was highly satisfied with result, and uncorrected visual acuity improved by over four lines. After surgery the patient needed low diopters for near as well as far distance. In the case of this patient, the ocular manifestations were detected and treated in adulthood. Nevertheless, early detection of ocular symptoms of Alport syndrome in young patients before renal failure could lead to timely start of the treatment and delay a possible renal transplant. In case of any suspicion of Alport syndrome it is advised to send the patient to a pediatrician, and at an older age to an internal medicine specialist, for further examination.
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  • 文章类型: Journal Article
    保守的色氨酸残基对于脊椎动物晶状体中β/γ-晶状体蛋白的结构和稳定性至关重要。在衰老过程中,其中镜片连续暴露于紫外线照射和其他环境压力下,β/γ-晶状体蛋白中色氨酸残基的氧化被触发并不同程度地影响晶状体蛋白。犬尿氨酸衍生物,由色氨酸氧化形成,积累,导致β/γ-晶状体蛋白不稳定和不溶解,这与年龄相关性白内障的形成有关。为了解色氨酸修饰对人βB2-晶状体蛋白结构和稳定性的影响,考虑到其与犬尿氨酸在结构和亲水性上的相似性,五个色氨酸残基被突变为苯丙氨酸。在所有突变体中,W59F和W151F改变了βB2-晶状蛋白-W59F的稳定性和均寡聚化促进了四聚化,而W151F阻断了寡聚化。大多数W59F二聚体在一个月内转化为四聚体,分离的W59F二聚体和四聚体表现出不同的结构和疏水性,这意味着βB2-晶状体蛋白的生化特性随时间而变化。通过使用SAXS,我们发现溶液中βB2-晶状体蛋白的二聚体类似于晶格βB1-晶状体蛋白二聚体(面),而溶液中βB2-晶状体蛋白的四聚体类似于其晶格四聚体(结构域交换)。我们的结果表明,βB2-晶状体蛋白的同源寡聚化包括潜在的亚基间反应,比如解离,展开,并在溶液中将二聚体重新形成四聚体。W>F突变体可用于研究晶状体中βB2-晶状体蛋白的不同折叠状态。
    Conserved tryptophan residues are critical for the structure and the stability of β/γ-crystallin in the lenses of vertebrates. During aging, in which the lenses are continuously exposed to ultraviolet irradiation and other environmental stresses, oxidation of tryptophan residues in β/γ-crystallin is triggered and impacts the lens proteins to varying degrees. Kynurenine derivatives, formed by oxidation of tryptophan, accumulate, resulting in destabilization and insolubilization of β/γ-crystallin, which correlates with age-related cataract formation. To understand the contribution of tryptophan modification on the structure and stability of human βB2-crystallin, five tryptophan residues were mutated to phenylalanine considering its similarity in structure and hydrophilicity to kynurenine. Among all mutants, W59F and W151F altered the stability and homo-oligomerization of βB2-crystallin-W59F promoted tetramerization whereas W151F blocked oligomerization. Most W59F dimers transformed into tetramer in a month, and the separated dimer and tetramer of W59F demonstrated different structures and hydrophobicity, implying that the biochemical properties of βB2-crystallin vary over time. By using SAXS, we found that the dimer of βB2-crystallin in solution resembled the lattice βB1-crystallin dimer (face-en-face), whereas the tetramer of βB2-crystallin in solution resembled its lattice tetramer (domain-swapped). Our results suggest that homo-oligomerization of βB2-crystallin includes potential inter-subunit reactions, such as dissociation, unfolding, and re-formation of the dimers into a tetramer in solution. The W>F mutants are useful in studying different folding states of βB2-crystallin in lens.
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