Lens, Crystalline

Lens,结晶
  • 文章类型: Case Reports
    一名29岁的男子被长期介绍,稳定,在远程彩弹伤的情况下单侧视力丧失。他的检查值得注意的是感觉外斜视以及后粘连的多个病灶,白色透镜状材料的片段和完全完整的囊内的透镜状细胞岛,以及受影响眼睛的严重小带性损害。大多数核晶状体材料不存在。患者被诊断为创伤后晶状体吸收,并接受了系统分析,囊切开术,切除残余透镜状材料,并放置了一个沟晶状体,手术后视力和眼线显着改善。我们的报告独特地强调了在存在完整的前囊和后囊的情况下,在吸收的晶状体中识别出Soemmering环,以及尽管治疗延迟了多年,但手术修复后成功的屈光和感觉运动结果。
    A 29-year-old man presented with longstanding, stable, unilateral vision loss in the setting of a remote paintball injury. His examination was notable for a sensory exotropia as well as multiple foci of posterior synechiae, segments of white lenticular material and islands of lenticular cells within a grossly intact capsule, and severe zonular compromise in the affected eye. The majority of the nuclear lens material was absent. The patient was diagnosed with post-traumatic lens absorption and underwent synechialysis, capsulotomy, excision of remnant lenticular material, and placement of a sulcus lens, with significant improvement in visual acuity and ocular alignment following surgery. Our report uniquely highlights identification of a Soemmering\'s ring in an absorbed lens in the presence of an intact anterior and posterior capsule as well as successful refractive and sensorimotor outcomes following surgical repair despite delay in treatment of many years.
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  • 文章类型: Journal Article
    我们试图评估生长分化因子(GDF)-15治疗抑制上皮间质转化(EMT)和减轻转化生长因子β2(TGFβ2)诱导的晶状体混浊的功效。
    为了测试GDF-15是否是防止EMT的分子,我们用GDF-15在神经祖细胞中预处理培养物,视网膜色素上皮细胞,和晶状体上皮细胞,然后用促进EMT的因子治疗,分别为GDF-11和TGFβ2。为了进一步研究GDF-15减轻晶状体混浊的功效,我们使用小鼠晶状体外植体培养来模拟继发性白内障。我们用GDF-15预处理晶状体培养物,然后加入TGFβ2以形成晶状体混浊(每组n=3)。Westernblot和定量逆转录聚合酶链反应(qRT-PCR)检测EMT蛋白和基因表达,分别。
    在细胞培养中,GDF-15预处理显著减弱了用GDF-11或TGFβ2处理诱导的培养细胞中的EMT标记表达。在晶状体外植体培养中,GDF-15预处理还减少了由暴露于TGFβ2引起的小鼠晶状体不透明度。
    我们的结果表明,GDF-15可以缓解TGFβ2诱导的EMT,并且是减缓或预防白内障手术后后囊混浊(PCO)进展的潜在治疗剂。
    白内障是全球失明的主要原因,目前唯一的治疗包括手术摘除晶状体和更换人工晶状体。然而,PCO,也称为继发性白内障,是白内障手术后常见的并发症。开发减缓PCO进展的佐剂将有益于前部并发症领域。
    UNASSIGNED: We sought to evaluate the efficacy of growth differentiation factor (GDF)-15 treatment for suppressing epithelial-mesenchymal transition (EMT) and alleviating transforming growth factor β2 (TGFβ2)-induced lens opacity.
    UNASSIGNED: To test whether GDF-15 is a molecule that prevents EMT, we pretreated the culture with GDF-15 in neural progenitor cells, retinal pigment epithelial cells, and lens epithelial cells and then treated with factors that promote EMT, GDF-11, and TGFβ2, respectively. To further investigate the efficacy of GDF-15 on alleviating lens opacity, we used mouse lens explant culture to mimic secondary cataracts. We pretreated the lens culture with GDF-15 and then added TGFβ2 to develop lens opacity (n = 3 for each group). Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to measure EMT protein and gene expression, respectively.
    UNASSIGNED: In cell culture, GDF-15 pretreatment significantly attenuated EMT marker expression in cultured cells induced by treatment with GDF-11 or TGFβ2. In the lens explant culture, GDF-15 pretreatment also reduced mouse lens opacity induced by exposure to TGFβ2.
    UNASSIGNED: Our results indicate that GDF-15 could alleviate TGFβ2-induced EMT and is a potential therapeutic agent to slow or prevent posterior capsular opacification (PCO) progression after cataract surgery.
    UNASSIGNED: Cataracts are the leading cause of blindness worldwide, with the only current treatment involving surgical removal of the lens and replacement with an artificial lens. However, PCO, also known as secondary cataract, is a common complication after cataract surgery. The development of an adjuvant that slows the progression of PCO will be beneficial to the field of anterior complications.
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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: Journal Article
    目的:晶状体的半脱位(EctopiaLentis,EL)可导致明显的视力损害,并可作为诸如Marfan综合征之类的遗传性疾病的诊断标准。没有既定的标准来诊断和量化EL。我们前瞻性地研究了健康受试者的小带纤维插入与角膜缘(ZLD)之间的距离,作为评估晶状体位置的参数,量化EL并提供规范数据。
    方法:这种前瞻性,观察,横断面研究包括150名健康参与者的150只眼睛(平均年龄28岁,范围4-68)。用0.5%的托吡卡胺和2.5%的去氧肾上腺素滴眼液对学生进行扩张。ZLD在裂隙灯处的散瞳中测量为晶状体表面上带状纤维的最中心可见插入与角膜巩膜缘之间的距离。记录垂直瞳孔直径(PD)和屈光不正。如果带状纤维插入不可见,角膜缘和瞳孔边缘之间的距离记录为ZLD。
    结果:检查了145只右眼和5只左眼。93%的研究对象是白种人,7%是亚洲人。在可见小带纤维插入的眼睛中(n=76只眼睛),ZLD为1.30±0.28mm(平均值±SD,范围为0.7-2.1),PD为8.79±0.57mm(7.5-9.8)。在剩下的74只眼睛里,ZLD为1.38±0.28mm(0.7-2.1),PD为8.13±0.58mm(6.7~9.4)。对于所有的眼睛,ZLD为1.34±0.29mm(0.7-2.1),PD为8.47±0.66mm(6.7-9.8)。屈光不正和性别对ZLD无显著影响。较小的PD和年龄较大与较大的ZLD相关(分别为P<0.001和P=0.036)。
    结论:健康受试者的平均ZLD为1.34mm。年龄较大与ZLD较大相关。这些规范数据将有助于诊断和量化EL。
    OBJECTIVE: Subluxation of the crystalline lens (Ectopia Lentis, EL) can lead to significant visual impairment and serves as a diagnostic criterion for genetic disorders such as the Marfan syndrome. There is no established criterion to diagnose and quantify EL. We prospectively investigated the distance between the zonular fibre insertion and the limbus (ZLD) in healthy subjects as a parameter to assess the position of the lens, quantify EL and provide normative data.
    METHODS: This prospective, observational, cross-sectional study includes one-hundred-fifty eyes of 150 healthy participants (mean age 28 years, range 4-68). Pupils were dilated with tropicamide 0.5% and phenylephrine 2.5% eyedrops. ZLD was measured in mydriasis at the slit lamp as the distance between the most central visible insertions of the zonular fibres on the lens surface and the corneoscleral limbus. Vertical pupil diameter (PD) and refractive error were recorded. If zonular fibre insertions were not visible, the distance between limbus and the pupillary margin was recorded as ZLD.
    RESULTS: 145 right and 5 left eyes were examined. 93% of study subjects were Caucasian, 7% were Asian. In eyes with visible zonular fibre insertions (n = 76 eyes), ZLD was 1.30 ± 0.28 mm (mean ± SD, range 0.7-2.1) and PD was 8.79 ± 0.57 mm (7.5-9.8). In the remaining 74 eyes, ZLD was 1.38 ± 0.28 mm (0.7-2.1), and PD was 8.13 ± 0.58 mm (6.7-9.4). For all eyes, ZLD was 1.34 ± 0.29 mm (0.7-2.1), and PD was 8.47 ± 0.66 mm (6.7-9.8). Refractive error and sex did not significantly affect ZLD. Smaller PD and older age were associated with larger ZLD (P < 0.001 and P = 0.036, respectively).
    CONCLUSIONS: Average ZLD was 1.34 mm in eyes of healthy subjects. Older age correlated with larger ZLD. These normative data will aid in diagnosing and quantifying EL.
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  • 文章类型: Journal Article
    探讨男性和女性之间胎龄(GA)与出生体重(BW)百分位数和眼部几何形状之间关系的差异。
    古腾堡早产儿眼科研究涉及对成年人进行前瞻性眼科检查,18至52岁,谁是早产或足月出生,在德国。通过单变量和多变量线性回归分析评估主要结局指标的GA和BW百分位数之间的关联。主要结果测量为中央角膜厚度,角膜半径,前房深度,透镜厚度,后段长度,中央凹厚度。分析了潜在的性别特异性差异和按性别进行的效应修饰。
    这项研究涉及438名参与者(245名女性,193名男性),平均年龄28.6±8.7岁。在女性参与者中,中央凹厚度与较高的GA呈负相关(B=-2.99;P<0.001)。同样,男性参与者还显示中央凹厚度与GA之间呈负相关(B=-4.27;P<0.001).具有效应修正的多变量模型表明,中心凹厚度随着GA的降低而较厚。GA的效果改变与性别和中央凹厚度之间存在关联,证明GA对男性参与者中央凹厚度的影响更明显(B=1.29;P=0.04)。
    这项研究确定了较低的GA和较厚的中央中央凹厚度之间的性别特异性相关性,表明该生物特征参数与GA有关的发展轨迹存在差异。中央凹厚度较厚可能会影响成年期早产儿的视力,对男性的影响更为明显,并且在以后的生活中可能容易患上与年龄有关的疾病。性别不影响GA或BW百分位数与其他眼部几何参数的关联。
    UNASSIGNED: To explore differences in the relationship between gestational age (GA) and birth weight (BW) percentile and ocular geometry between males and females.
    UNASSIGNED: The Gutenberg Prematurity Eye Study involved a prospective ophthalmic examination of adults, aged 18 to 52 years, who were born preterm or at term, in Germany. The associations between GA and BW percentile on the main outcome measures were evaluated by uni- and multivariable linear regression analyses. The main outcome measures were central corneal thickness, corneal radius, anterior chamber depth, lens thickness, posterior segment length, and central foveal thickness. Potential sex-specific differences and an effect modification by sex were analyzed.
    UNASSIGNED: This study involved 438 participants (245 females, 193 males) with an average age of 28.6 ± 8.7 years. In female participants, central foveal thickness was negatively associated with a higher GA (B = -2.99; P < 0.001). Similarly, male participants also demonstrated a negative association between central foveal thickness and GA (B = -4.27; P < 0.001). The multivariable model with effect modification revealed that the central foveal thickness was thicker with lower GA. There was an association between the effect modification of GA with sex and central foveal thickness, demonstrating a more pronounced effect of GA on central foveal thickness in male participants (B = 1.29; P = 0.04).
    UNASSIGNED: This study identified a sex-specific correlation between lower GA and thicker central foveal thickness, suggesting differences in the developmental trajectory of this biometric parameter concerning GA. A thicker central foveal thickness might affect the visual acuity of individuals born preterm in adulthood, with a more pronounced impact in males and a potential predisposition to age-related diseases later in life. Sex did not influence the association of GA or BW percentile to other ocular geometric parameters.
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  • 文章类型: Journal Article
    优化和评估从甚高频数字超声机器人扫描仪(ArtemisInsight100)生成的拱顶预测公式的准确性。通过回顾性研究分析人工晶状体(ICL)植入手术后一个月获得的晶状体拱顶(LVa)与预测拱顶(LVp)之间的关系。并建立了优化的配方。然后,在一项前瞻性研究中,通过比较LVa和来自优化公式(LVop)的预测拱顶,评估了优化拱顶预测公式的准确性.回顾性研究包括77例患者(133只眼),而前瞻性研究招募了90例患者(170只眼)。术后1个月LVp和LVa差异有统计学意义(P<0.05),LVa与LVp的线性回归分析拟合良好(R2=0.68)。优化后的拱顶预测公式为LVop(μm)=1.21×LVp(μm)+124.73。在验证研究中,LVop和LVa差异无统计学意义(P=0.10),Bland-Altman分析显示LVop和LVa具有良好的一致性。优化后的拱顶预测公式可以预测ICL植入手术后的实际左心室。有助于选择合适的ICL大小并减少重新操作的需要。
    To optimize and evaluate the accuracy of the vault-predicting formula generated from a very high-frequency digital ultrasound robotic scanner (Artemis Insight 100). The relationship between the achieved lens vault (LVa) at one month after intraocular collamer lens (ICL) implantation surgery and the predicted vault (LVp) was analyzed by a retrospective study, and an optimized formula was built up. Then, the accuracy of the optimized vault-predicting formula was evaluated in a prospective study by comparing the LVa and the predicted vault from the optimized formula (LVop). The retrospective study included 77 patients (133 eyes) while the prospective study enrolled 90 patients (170 eyes). The difference between LVp and LVa at one month after surgery was statistically significant (P < 0.05), and the linear regression analysis of LVa against LVp yielded a good fit (R2 = 0.68). The optimized vault-predicting formula was LVop (μm) = 1.21 × LVp (μm) + 124.73. In the validation study, the difference between LVop and LVa was not statistically significant (P = 0.10), and a good agreement between LVop and LVa was shown by Bland-Altman analysis. The optimized vault-predicting formula could predict the actual LV after ICL implantation surgery, help to select an appropriate ICL size and reduce the need for re-operation.
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  • 文章类型: Journal Article
    长寿的晶状体纤维细胞需要强大的细胞保护功能来抵抗氧化损伤,以维持其止血和活力;然而,潜在的机制在很大程度上是模糊的。在这项研究中,我们揭示了一种保护晶状体纤维细胞免受氧化应激诱导的细胞死亡的新机制。我们发现机械激活的连接蛋白(Cx)半通道(HCs)介导谷胱甘肽(GSH)向雏鸡胚胎成纤维细胞(CEF)和原代晶状体纤维细胞的转运,导致H2O2和紫外线B诱导的细胞内活性氧的积累减少,保护晶状体纤维细胞免受细胞凋亡和坏死。此外,同型Cx50或Cx46和异型Cx50/Cx46形成的HC对机械敏感,可以将GSH转运到CEF细胞中。值得注意的是,机械活化的Cx50HCs比Cx46HCs具有更大的GSH转运能力。始终如一,单晶状体纤维细胞中Cx50的缺乏导致较高水平的氧化应激。此外,与中央核心长晶状体纤维相比,表达全长Cxs的外皮质短晶状体纤维细胞对氧化损伤具有更大的抵抗力。一起来看,我们的结果表明,培养的上皮细胞和分离的成纤维细胞中的间质液流动对CxHCs的激活表明,HCs可以作为GSH穿过细胞膜的途径,从而提供抗氧化应激的保护.
    Long-lived lens fiber cells require a robust cellular protective function against oxidative insults to maintain their hemostasis and viability; however, the underlying mechanism is largely obscure. In this study, we unveiled a new mechanism that protects lens fiber cells against oxidative stress-induced cell death. We found that mechano-activated connexin (Cx) hemichannels (HCs) mediate the transport of glutathione (GSH) into chick embryonic fibroblasts (CEF) and primary lens fiber cells, resulting in a decrease in the accumulation of intracellular reactive oxygen species induced by both H2O2 and ultraviolet B, providing protection to lens fiber cells against cell apoptosis and necrosis. Furthermore, HCs formed by both homomeric Cx50 or Cx46 and heteromeric Cx50/Cx46 were mechanosensitive and could transport GSH into CEF cells. Notably, mechano-activated Cx50 HCs exhibited a greater capacity to transport GSH than Cx46 HCs. Consistently, the deficiency of Cx50 in single lens fiber cells led to a higher level of oxidative stress. Additionally, outer cortical short lens fiber cells expressing full length Cxs demonstrated greater resistance to oxidative injury compared to central core long lens fibers. Taken together, our results suggest that the activation of Cx HCs by interstitial fluid flow in cultured epithelial cells and isolated fiber cells shows that HCs can serve as a pathway for moving GSH across the cell membrane to offer protection against oxidative stress.
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  • 文章类型: Journal Article
    关于人晶状体上皮细胞(HLEC)对电离辐射暴露的反应的知识对于理解辐射防护和放射治疗领域中关注的辐射白内障的机制很重要。然而,长期暴露后HLECs的生物学效应尚未得到充分探索。这里,我们研究了在各种剂量率下暴露于光子束后,γ-H2AX焦点作为HLEC中DNA双链断裂(DSB)和细胞存活的标志物的时间动力学(即,以1.82、0.1和0.033Gy/min进行150kVpX射线,和137Csγ射线在0.00461Gy/min(27.7cGy/h)和0.00081Gy/min(4.9cGy/h)下,与人肺成纤维细胞(WI-38)相比。并行,我们使用生物物理模型量化了DSB的恢复和细胞存活.研究表明,HLEC的DSB修复率低于WI-38细胞。在0.033-1.82Gy/min的剂量率范围内,剂量率对两种细胞系中的细胞存活没有显著影响。相比之下,与模型预测相比,实验残留γ-H2AX病灶显示出相反的剂量率效应(IDRE),强调IDREs在评估辐射对晶状体的影响方面的重要性。
    The knowledge on responses of human lens epithelial cells (HLECs) to ionizing radiation exposure is important to understand mechanisms of radiation cataracts that are of concern in the field of radiation protection and radiation therapy. However, biological effects in HLECs following protracted exposure have not yet fully been explored. Here, we investigated the temporal kinetics of γ-H2AX foci as a marker for DNA double-strand breaks (DSBs) and cell survival in HLECs after exposure to photon beams at various dose rates (i.e., 150 kVp X-rays at 1.82, 0.1, and 0.033 Gy/min, and 137Cs γ-rays at 0.00461 Gy/min (27.7 cGy/h) and 0.00081 Gy/min (4.9 cGy/h)), compared to those in human lung fibroblasts (WI-38). In parallel, we quantified the recovery for DSBs and cell survival using a biophysical model. The study revealed that HLECs have a lower DSB repair rate than WI-38 cells. There is no significant impact of dose rate on cell survival in both cell lines in the dose-rate range of 0.033-1.82 Gy/min. In contrast, the experimental residual γ-H2AX foci showed inverse dose rate effects (IDREs) compared to the model prediction, highlighting the importance of the IDREs in evaluating radiation effects on the ocular lens.
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  • 文章类型: Journal Article
    扫视后振荡(PSO)反映由瞳孔和晶状体相对于眼球的运动而不是眼球旋转引起的注视运动。这里,我们分析了年龄相关性黄斑变性(AMD)受试者的PSO特征,视网膜色素变性(RP),正常视力(NV)我们的目的是评估视力丧失者与健康对照组之间的PSO差异,因为PSO会影响每次扫视后的视网膜图像稳定性。
    参与者完成了水平扫视任务,并使用基于瞳孔的眼睛跟踪器测量了他们的凝视。用阻尼振荡模型描述了扫视后80至200ms周期内发生的振荡。我们比较了振幅,衰减时间常数,和三个不同组的PSO频率。我们还检查了这些PSO参数与振幅之间的相关性,峰值速度,和前面扫视的最后减速。
    视力丧失的受试者(AMD,n=6,RP,n=5)具有较大的振荡幅度,更长的衰减常数,频率低于NV受试者(n=7)。在所有三组中,振荡幅度都随着扫视减速的增加而增加。其他PSO参数,然而,与扫视幅度或峰值速度均未显示一致的相关性。
    由于异常的PSO,AMD和RP的扫视后固定稳定性降低。关于NV的差异不是由于扫视运动学的差异,这表明解剖和神经元变异会影响患者眼虹膜和晶状体的悬吊。
    UNASSIGNED: Post-saccadic oscillations (PSOs) reflect movements of gaze that result from motion of the pupil and lens relative to the eyeball rather than eyeball rotations. Here, we analyzed the characteristics of PSOs in subjects with age-related macular degeneration (AMD), retinitis pigmentosa (RP), and normal vision (NV). Our aim was to assess the differences in PSOs between people with vision loss and healthy controls because PSOs affect retinal image stability after each saccade.
    UNASSIGNED: Participants completed a horizontal saccade task and their gaze was measured using a pupil-based eye tracker. Oscillations occurring in the 80 to 200 ms post-saccadic period were described with a damped oscillation model. We compared the amplitude, decay time constant, and frequency of the PSOs for the three different groups. We also examined the correlation between these PSO parameters and the amplitude, peak velocity, and final deceleration of the preceding saccades.
    UNASSIGNED: Subjects with vision loss (AMD, n = 6, and RP, n = 5) had larger oscillation amplitudes, longer decay constants, and lower frequencies than subjects with NV (n = 7). The oscillation amplitudes increased with increases in saccade deceleration in all three groups. The other PSO parameters, however, did not show consistent correlations with either saccade amplitude or peak velocity.
    UNASSIGNED: Post-saccadic fixation stability in AMD and RP is reduced due to abnormal PSOs. The differences with respect to NV are not due to differences in saccade kinematics, suggesting that anatomic and neuronal variations affect the suspension of the iris and the lens in the patients\' eyes.
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  • 文章类型: Journal Article
    白内障疾病与晶状体的极长寿命晶状体蛋白的逐渐积累的氧化损伤密切相关。半胱氨酸氧化影响晶状体蛋白折叠,互动,和光散射聚集特别强烈,由于二硫键的形成。最大限度地减少晶状体蛋白聚集对于终身晶状体透明度至关重要,因此,人们可能会期望普遍存在的晶状体晶状体蛋白超家族(α和βγ)含有很少的半胱氨酸。然而,γ-晶状体蛋白的Cys含量远高于人类蛋白质的平均值。我们回顾了与这个长期难题相关的文献,并利用扩展的基因组数据库和改进的机器学习工具来预测蛋白质结构,以进一步研究它。我们观察到βγ-晶状体蛋白超家族的Cys保守性低;然而,在γ-晶状体蛋白中,Cys残基的空间定位通过进化被清晰地微调。我们认为,长期透镜透明度和高透镜光焦度的要求对透镜βγ-晶状体蛋白施加了竞争的进化压力,导致不同的适应:γ-晶状体蛋白中Cys含量高,而βB-晶状体蛋白中Cys含量低。水生物种需要比陆地物种更强大的镜头,这解释了许多鱼γ-(甚至β-)晶状体蛋白的高蛋氨酸含量。最后,我们讨论了结晶蛋白中含硫和芳香族残基之间的协同作用,并提出了未来的实验方向。
    Cataract disease is strongly associated with progressively accumulating oxidative damage to the extremely long-lived crystallin proteins of the lens. Cysteine oxidation affects crystallin folding, interactions, and light-scattering aggregation especially strongly due to the formation of disulfide bridges. Minimizing crystallin aggregation is crucial for lifelong lens transparency, so one might expect the ubiquitous lens crystallin superfamilies (α and βγ) to contain little cysteine. Yet, the Cys content of γ-crystallins is well above the average for human proteins. We review literature relevant to this longstanding puzzle and take advantage of expanding genomic databases and improved machine learning tools for protein structure prediction to investigate it further. We observe remarkably low Cys conservation in the βγ-crystallin superfamily; however, in γ-crystallin, the spatial positioning of Cys residues is clearly fine-tuned by evolution. We propose that the requirements of long-term lens transparency and high lens optical power impose competing evolutionary pressures on lens βγ-crystallins, leading to distinct adaptations: high Cys content in γ-crystallins but low in βB-crystallins. Aquatic species need more powerful lenses than terrestrial ones, which explains the high methionine content of many fish γ- (and even β-) crystallins. Finally, we discuss synergies between sulfur-containing and aromatic residues in crystallins and suggest future experimental directions.
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