晶状体蛋白与年龄相关性白内障研究进展

晶状体蛋白是晶状体内重要的结构蛋白,多种蛋白质的翻译后修饰(post translational modification, PTM)可引起晶状体蛋白结构、溶解度的改变并最终导致白内障形成,而另一些翻译后修饰则可能与晶状体蛋白的保护作用相关。特别是α晶状体蛋白分子伴侣活性的下降可导致其他晶状体蛋白的凝聚和酶的失活,与年龄相关性白内障(age-related cataract,ARC)的发生密切相关。年龄相关性白内障为多因素疾病,目前确切病因不明,手术仍是治疗年龄相关性白内障的主要手段,尚无有效可以延缓或预防该疾病的药物。本文就目前主要的晶状体蛋白与年龄相关性白内障的关系及研究进展进行综述。     

晶状体蛋白的外消旋化及其在白内障发病机制中的研究进展

外消旋化是老年人晶状体蛋白中重要的翻译后修饰类型.多项研究发现,随着年龄的增长,α-、β-及γ-晶状体蛋白中的部分L型氨基酸残基倾向于通过外消旋化反应转化为D型氨基酸残基,导致晶状体蛋白的构象改变,聚合形成的大分子蛋白质在晶状体核区和皮质中逐渐积累,晶状体蛋白失去了原有功能而不能维持晶状体的透明度.外消旋化在晶状体蛋白年龄相关性改变中的效应和参与程度,及其对白内障发生与进展的具体机制都值得进一步研究.     

DNA甲基化在晶状体发育及白内障中的研究进展

表观遗传学是指基因碱基序列在未发生改变的情况下调控基因表达的一门学科,其研究领域主要涉及DNA甲基化、组蛋白修饰和非编码RNA,其中DNA甲基化沉默基因的表达是表观遗传学重要的调控机制.DNA甲基化状态受环境因素的影响,而晶状体发育异常及白内障形成由多种致病因素决定,其中包括环境因素.因此,研究DNA甲基化在晶状体发育及白内障形成过程中的作用机制尤为重要.本文就近年来DNA甲基化在晶状体发育、年龄相关性白内障、并发性白内障、后发性白内障发病机制中的作用进行综述,通过对DNA甲基化在上述眼部疾病及晶状体发育过程中作用机制的认识及研究,有望在白内障临床治疗中开辟新的途径.     

晶体蛋白与白内障发病机制研究

白内障是严重影响人类健康的常见病、多发病。研究白内障的病因学及影响因素,是预防和治疗该病的有力措施。白内障主要是因晶状体的透光性改变所引发;晶状体的透光性是由晶体蛋白的有序结构所决定的。本文综述近年来有关晶体蛋白的组成与结构、翻译后修饰及热休克蛋白与白内障发病机制的关系。     

α-晶状体蛋白对维持晶状体透明性的功能研究进展

α-晶状体蛋白是眼晶状体细胞质的主要成分,由小热休克蛋白家族中的αA-晶状体蛋白和αB-晶状体蛋白组成.α-晶状体蛋白具有分子伴侣活性,还有调控细胞周期、增强基因组稳定性、防止压力诱导性细胞凋亡的作用.α-晶状体蛋白相关基因突变常引起遗传性白内障,是目前儿童盲的主要原因,而α-晶状体蛋白的多种改变可导致年龄相关性白内障.了解α-晶状体蛋白的功能有助于理解晶状体的发育及其正常功能的维持,为预防及治疗α-晶状体蛋白相关性白内障提供理论依据.就白内障发生机制、遗传定位及晶状体蛋白的功能进行综述.     

大鼠老化进程中晶状体蛋白水溶性向水不溶性的转变

目的:研究大鼠老化进程中晶状体蛋白由水溶性向水不溶性的转变特性,探讨对老年性白内障形成的可能作用.方法:采用双向电泳法,分析SD大鼠在老化进程中不同阶段(出生后1,8 d;2,8 wk;8 mo;1.5 a)晶状体蛋白α,β,γ由水溶性向水不溶性的时相性转变特性.结果:各年龄组大鼠晶状体蛋白水溶性及水不溶性成分的双向电泳图谱模式有较大相似性.结构蛋白αA2,αB2,βB2随老化进程,其水溶性成分均呈升高趋势;水不溶性成分中αA2,βB2含量亦随年龄增长而升高,αB2在大鼠出生8 mo后呈明显升高.晶状体蛋白自出生后8 wk起,即发生明显的翻译后修饰(蛋白斑点增加),尤其伴侣蛋白(αA2,αB2,同时也是结构蛋白)随老化其修饰成分增加十分明显,在水不溶性成分图谱中表现更为突出.出生后8 wk前,βB2晶状体蛋白无论在水溶性或水不溶性成分中含量均极少;发育渐趋成熟该蛋白含量快速增加;出生8 mo后成为晶状体蛋白中的主要成分,1.5 a起成为含量最高的成分.结论:在大鼠老化进程中,不同晶状体蛋白其水溶性及水不溶性成分的变化趋势呈现不同特性.同种晶状体蛋白在不同年龄段存在量和/或质的变化.大鼠成长过程中晶状体蛋白变性显见于出生后8 wk,其程度随老化而加重.     

蛋白质翻译后修饰与年龄相关性白内障

蛋白质翻译后修饰是指在mRNA被翻译成蛋白质后,对蛋白质上个别氨基酸残基进行共价修饰的过程.晶状体内存在多种蛋白质翻译后修饰,其中脱酰胺化、糖基化、氧化修饰不仅具有年龄相关性,而且可引起晶状体蛋白结构、溶解度的改变并最终导致自内障形成;而乙酰化、甲基化修饰则与晶状体蛋白的保护作用相关;其他翻泽后修饰与年龄相关性白内障之间的关系尚未明确.目前手术仍是治疗年龄相关性白内障的主要手段,尚无有效可以延缓或预防该疾病的药物.本文就目前主要的蛋白质翻译后修饰与年龄相关性白内障的关系以及针对蛋白质翻译后修饰的干预措施进行综述.

Abstract：

Cataract is the main cause of vision impairment, and age-related cataract is the most common type of cataract. Protein post-translational modification is the enzymatic processing of a polypeptide chain after translation from messenger RNA and after peptide bond formation has occurred. Deamidation,glycation and oxidation are age-related processes. They can change the structure or solubility of crystallin and result in the opacity of lens while acetylation and methylation may be related to the protection of lens protein.Although much effort has been directed towards slowing progression or preventing the occurrence of cataract,the management of cataract remains surgical. This review deals with the relations between different kinds of protein post-translational modification and age-related cataract as well as some protective methods aiming at the process of post-translational modification.     

糖基化对牛α-晶状体蛋白分子伴娘功能的作用

α-晶状体蛋白作为晶状体的主要结构蛋白，是维持晶状体结构和屈光特性的重要物质，其分子伴娘功能对保护晶状体透明具有决定性作用。糖基化可修饰α-晶状体蛋白，影响其分子伴娘功能，参与年龄相关性白内障和糖尿病性白内障的形成。本研究通过观察α-磷酸果糖(fructose-6-phosphate，F6P)和核糖对α-晶状体蛋白的修饰和影响，证实糖基化在白内障形成中的作用机制。     

αβ-晶状体蛋白在先天性白内障大鼠晶状体中免疫活性的变化

目的观察正常以及先天性白内障大鼠晶状体中出晶状体蛋白的免疫活性变化，探讨其与白内障发病的关系。方法分别摘取8周龄、10周龄、12周龄、14周龄正常对照组以及先天性白内障大鼠晶状体，应用抗生物素蛋白-生物素-过氧化物酶复合体法，观察不同时期大鼠晶状体中αβ-晶状体蛋白的免疫活性变化。结果αβ-晶状体蛋白在各周龄正常大鼠晶状体上皮细胞及纤维部具有较高的表达。在8周龄、10周龄先天性白内障大鼠晶状体上皮细胞及纤维部可观察到与正常对照组相同的较强的免疫活性，而12周龄、14周龄鼠的白内障晶状体纤维部毋晶状体蛋白的免疫活性明显低于正常对照组。结论在12周龄、14周龄先天性白内障大鼠晶状体纤维部，出晶状体蛋白的免疫活性减弱，在白内障形成过程中出晶状体蛋白可能被一些蛋白酶水解分化，从而促进白内障的形成。     

中药防治糖性白内障的作用机制研究进展

糖性白内障是一种代谢性眼病,它的发生与体内多元醇通路异常活跃、晶状体上皮细胞的凋亡、自由基对晶状体的氧化损伤、晶状体信号转导的异常以及晶状体蛋白质的翻译后修饰变性等有着密切的关系.中药可通过作用于以上环节而起到预防或治疗糖性白内障的作用.     

Strabisme Alternant - Etude clinique - traitement

The author defines motor and sensory alternation: the term alternation should not be used in isolation, it should always be accompanied by the name of the parameter concerned. Sensory alternation is always found together with motor alternation but the reverse is not true.The examining criteria for a diagnosis of sensory alternation are given, sensory alternation must not be confused with alternating inhibition. Working from clinical observations of cases of motor alternating strabismus, the author selects 2 types of binocular sensory relations which allow one to differentiate between:- cases of primary alternating strabismus- cases of secondary alternating strabismusThese forms will develop in different ways; in both cases a cure is possible providing that the right treatment is prescribed and once prescribed carefully followed, etc. It is always a case of serious forms of strabismus whose developmental period is spread over several years.According to the authors, the frequency of cases of true primary strabismus is from 1–3%, the frequency of cases of secondary alternating strabismus varies according to the type of therapy practised on cases of monocular strabismus with amblyopia. These latter will become cases of alternating strabismus under the influence of certain types of therapy carried out over several years (penalization, rocking, alternated occlusion, etc...).Experimental data on kittens confirm clinical data; kittens placed in abnormal environments during the sensitive period will show modification in the distribution of cortical cells and the absence of binocular cells (either because the excitation of the two eyes was not simultaneous, or not identical: artificial strabismus, occlusion, opaque glasses). This disturbances become irreversible after a certain period of exposure (a function of age, length of exposure, etc...).It is thus necessary to bear in mind: 1) the iatrogenic risks of certain orthoptic treatments, 2) the necessity for a binocular form of treatment as soon as possible, as once a certain stage is passed, cortical plasticity diminishes and the elaboration of normal binocular relations becomes impossible.

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Effects of Adenosine Agonists on Intraocular Pressure and Aqueous Humor Dynamics in Cynomolgus Monkeys

The effects of single or multiple topical doses of the relatively selective A₁adenosine receptor agonists (R)-phenylisopropyladenosine (R-PIA) and N⁶-cyclohexyladenosine (CHA) on intraocular pressure (IOP), aqueous humor flow (AHF) and outflow facility were investigated in ocular normotensive cynomolgus monkeys. IOP and AHF were determined, under ketamine anesthesia, by Goldmann applanation tonometry and fluorophotometry, respectively. Total outflow facility was determined by anterior chamber perfusion under pentobarbital anesthesia. A single unilateral topical application of R-PIA (20–250 μg) or CHA (20–500 μg) produced ocular hypertension (maximum rise=4.9 or 3.5 mmHg) within 30 min, followed by ocular hypotension (maximum fall=2.1 or 3.6 mmHg) from 2–6 hr. The relatively selective adenosine A₂antagonist 3,7-dimethyl-1-propargylxanthine (DMPX, 320 μg) inhibited the early hypertension, without influencing the hypotension. Neither 100 μg R-PIA nor 500 μg CHA clearly altered AHF. Total outflow facility was increased by 71% 3 hr after 100 μg R-PIA. In conclusion, the early ocular hypertension produced by topical adenosine agonists in cynomolgus monkeys is associated with the activation of adenosine A₂receptors, while the subsequent hypotension appears to be mediated by adenosine A₁receptors and results primarily from increased outflow facility.