高血糖“代谢记忆”与糖尿病视网膜病变的关系

大规模临床试验表明糖尿病后期血糖即使有效控制,糖尿病各种并发症仍然持续进展,即高糖“记忆”效应.高糖“记忆”引起糖尿病视网膜病变(diabetic retinopathy,DR)的机制尚不清楚,氧化应激被认为具有关键作用.高糖导致视网膜上细胞线粒体结构与功能障碍,活性氧不断释放并激活下游的多条致病通路,造成“代谢记忆”在视网膜上产生,DR不断进展.此外,非酶促糖基化作用、基因表观遗传修饰以及炎症与凋亡因素等机制也可能参与其中.     

“代谢记忆”现象与糖尿病视网膜病变

“代谢记忆”现象是指,糖尿病患者发病时,如果高血糖不能及时调整到正常,即使后来血糖持续稳定在正常水平,其慢性并发症（包括视网膜病变）仍然会发生发展,难以逆转。糖尿病视网膜病变是一种常见的糖尿病并发症。现就“代谢记忆”与糖尿病视网膜病变发病的关系、“代谢记忆”现象的产生机制以及抗“代谢记忆”药物等研究状况进行简要综述,以期为糖尿病视网膜病变的防治提供新的策略。     

重视表观遗传修饰在视网膜血管性疾病中的调控作用

表观遗传学已成为生物医学领域的研究热点,疾病的发生不仅与遗传因素有关,而且还受到环境因素的影响。老年性黄斑变性、糖尿病视网膜病变等视网膜血管性疾病是一类以视网膜血管病变为核心病理改变的不可逆致盲性眼病,是多种环境因素和基因相互作用的结果。表观遗传学的调控方式主要包括DNA甲基化、组蛋白修饰和非编码RNA调控。表观遗传机制介导环境因素,参与视网膜血管病变相关基因的调控,影响疾病最终的发生发展。因此,眼科医生应重视表观遗传在视网膜血管性疾病中的作用,追踪表观遗传学方法在视网膜血管性疾病治疗中取得的进展,关注表观遗传学的应用前景。寻找这些疾病的表观调控因子,不仅可以加深对这些疾病发生机制的认识,同时还能为这些疾病的诊断和治疗提供新的思路。     

DNA甲基化修饰在眼科疾病发病进程中的作用研究进展

许多眼科疾病的发生发展与遗传、环境两大因素密切相关,其中表观遗传修饰是连接遗传与环境因素的重要纽带,能够通过影响基因转录或翻译影响相关基因的表达水平,在眼病的发病进程中发挥作用。DNA甲基化修饰(DNA methylation)是表观遗传修饰的重要组成部分,通常由从头甲基化、维持甲基化和去甲基化三个过程调节,在调控基因表达方面具有重要意义。目前,研究人员发现DNA甲基化修饰在角膜内皮的损伤修复、线粒体动力学调控与糖尿病视网膜病变、氧化应激反应与白内障等眼科疾病中发挥重要作用,为相关眼病的治疗提供了新的思路。本文就DNA甲基化修饰在相关眼病发展进程中的作用研究进展进行简要综述,为眼病的筛查、诊断与治疗提供新的视角与方向。     

视网膜电图诊断早期糖尿病视网膜病变

视网膜电图是一项评价视网膜功能的客观检查,适用于评价多种眼科疾病的视网膜功能情况。近年研究发现,在早期糖尿病患者中,视网膜电图能够发现先于眼底视网膜形态学改变的功能变化,这一点为糖尿病视网膜病变的病理机制研究、早期诊断、以及预后评估提供了新思路,进而可能为治疗糖尿病视网膜病变提供新途径。我们就运用视网膜电图诊断早期糖尿病视网膜病变进行综述。     

从组蛋白及组蛋白修饰看视网膜疾病

视网膜疾病包括年龄相关性黄斑变性(AMD)、糖尿病视网膜病变(DR)、视网膜色素上皮变性(RP)和营养不良、视网膜和脉络膜肿瘤等,是一组与视网膜及其神经和血管相关的疾病.尽管基因变异和单核苷酸多态性等遗传学因素所造成的基因表达的改变已被证明与这些疾病的发病机制有密切关系,但在基因序列不发生改变的情况下,长期内在及外在环境变化造成的可遗传性基因表达的改变正受到研究者的关注.近年来越来越多的证据支持至少部分视网膜疾病的发病机制与表观遗传,特别是组蛋白及组蛋白修饰有关.相关研究的进展使我们加深了对视网膜疾病病理机制的认识.     

表观遗传调控在糖尿病视网膜病变中的研究进展

遗传和环境因素均参与糖尿病及其并发症的病理过程，表观遗传调控在其中的作用也日渐明确。糖尿病及其并发症中的主要病理过程如高血糖、氧化应激、炎症等均会导致表观遗传调控的异常，从而影响染色质结构和基因表达，而这些染色质表观遗传修饰的持续存在和糖尿病相关的代谢记忆现象相联系。表现机制相关的药物和治疗手段的研发或将成为糖尿病及相关并发症靶向治疗的新方面。     

视网膜神经节细胞相关的表观遗传学研究进展

表观遗传是一种基因表达和功能的改变而非DNA序列的改变,且具有可逆性、可遗传性的调节方式.目前,表观遗传机制的研究主要集中在DNA甲基化、组蛋白修饰、染色体重塑及非编码RNA等.尽管青光眼的病因十分复杂,但最终通路都是视网膜神经节细胞(retinal ganglion cells,RGC)进行性死亡和视神经纤维的丢失.研究表明,表观遗传通过上述机制对RGC的生长发育、凋亡及神经元再生进行调控,揭示了青光眼发病过程中RGC的表观遗传调控机制,可能为青光眼的治疗提供新思路.     

糖尿病视网膜病变相关“代谢记忆”的研究进展

糖尿病患者若高血糖不能及时有效控制，即使后期血糖长期控制良好，仍可能发生糖尿病慢性并发症即为高血糖的“代谢记忆”效应。糖尿病视网膜病变（DR）是糖尿病最常见的微血管并发症之一，糖尿病早期高血糖如不能得到及时控制，后期及时严格控制血糖，DR仍会发生、发展。多项糖尿病临床试验研究发现早期严格控制血糖可以延缓DR的病程，但糖尿病血管性应激物仍然处于高水平。炎症因子瀑布、氧化应激增强以及表观遗传修饰的变化等在高血糖“代谢记忆”现象发生发展中发挥重要作用。     

糖尿病视网膜病变发生发展的全身及眼局部相关因素

糖尿病性视网膜病变(diabetic retinopathy,DR)是最为常见的致盲性眼底病变之一,其发病机制不明。长期以来,早期对于糖尿病性视网膜病变的治疗只是单纯控制血糖,但这并不能完全阻止糖尿病性视网膜病变的进一步发展。因此,研究全身及眼局部相关因素的影响作用十分重要。近年来,国内外大量研究认为,许多全身及眼局部因素对糖尿病性视网膜病变发生发展起重要作用。本文综述此方面成果,为最终通过全身及眼局部的综合干预为早期防治糖尿病性视网膜病变提供思路。     

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.