外泌体在原发性开角型青光眼中的研究进展

外泌体同原发性开角型青光眼(POAG)的发病及诊疗过程有着多种关联。POAG相关蛋白及细胞因子可经外泌体释放调节房水循环;外泌体通过侵袭性伪足及基质金属蛋白酶活性调控细胞外基质降解和重塑影响小梁网的稳定性,外泌体还可与小胶质细胞相互作用介导视神经损伤。由于外泌体内容物的特异性使其可能作为POAG的诊断标志物。治疗方面通过间充质干细胞移植,利用其自身分泌的外泌体可以促进POAG患者的视神经节细胞存活。本研究即对外泌体在POAG的发病机制、诊断及治疗中的作用进行综述。     

外泌体在青光眼诊疗中的作用研究进展

外泌体是由各种细胞分泌产生, 广泛存在于生物体液中的纳米级脂质双分子层结构小囊泡, 其内容物复杂, 具有多种生物学功能。外泌体在青光眼的发生和发展中扮演重要作用, 眼内外泌体通过运输青光眼相关蛋白、调节Wnt信号通路、影响细胞外基质周转等参与小梁网细胞调节, 从而影响房水循环;小胶质细胞外泌体介导视网膜神经炎症和相关的炎症信号通路。此外, 眼内液中外泌体稳定存在, 其中差异性表达的蛋白质、RNA等内容物使外泌体具有作为青光眼生物标志物的潜力。在青光眼治疗方面, 干细胞源性外泌体抑制胶质细胞活化及神经炎症, 减少视网膜神经节细胞的损失, 起到神经保护作用。外泌体可通过血-视网膜屏障, 输送神经营养因子、药物或其他治疗分子到靶细胞中, 调节靶细胞的功能, 为青光眼视神经退行性病变提供了新的治疗手段。本文总结国内外青光眼与外泌体领域的研究进展, 并对外泌体在青光眼的发生和发展、诊断及治疗中的作用及机制进行综述, 以期为早期诊断和治疗青光眼提供新思路。     

非动脉炎性前部缺血性视神经病变的治疗进展

非动脉炎性前部缺血性视神经病变(NAION)作为一组常见的严重危害视功能的视神经疾病,是由于睫状后短动脉灌注不足,使视神经发生急性缺血、结构以及功能紊乱,最终导致视力下降、甚至视力丧失。该病的病因和发病机制复杂,目前认为是局部解剖因素、全身血管危险因素等多因素共同参与,导致治疗上没有明确、统一、公认的治疗方案,早期发现、诊断和治疗对NAION的预后影响极大。目前治疗主要包括:对因治疗、药物治疗、中医治疗、联合用药、视神经鞘减压术、辅助治疗及外泌体治疗。随着近年各类抗NAION药物的不断发展和运用,提出了多种治疗方法,尤其以外泌体为研究热点,被广泛关注。为了更好地治疗NAION、提高治愈率、指导临床工作,本文主要对NAION的近年来的治疗进展做出以下综述。     

神经生长因子联合传统用药对前部缺血性视神经病变的疗效

目的:评价神经生长因子(nerve growth factor,NGF)对前部缺血性视神经病变视神经保护有效性及安全性。方法:对343例343眼前部缺血性视神经病变患者采用肌肉注射鼠NGF30μgqd,连续注射3wk,同时给予扩血管药、神经营养剂进行治疗。记录治疗前后的矫正logMAR视力、视野平均缺损值(mean deviation,MD)、视诱发电位潜伏期(pattern visual evoked potential,P-VEP)等指标并进行分析和统计。对治疗过程中的不良反应进行统计以评价其安全性。结果:应用NGF治疗后,患者的视力较治疗前显著提高,视野MD值较治疗前显著降低,P-VEP显示潜伏期较治疗前显著缩短,差异具有统计学意义(P<0.05)。本研究共发生实验室指标不良事件18例,发生率为5.25%。结论:鼠NGF联合扩血管药和神经营养剂治疗前部缺血性视神经病变疗效满意,不良反应少。     

前部缺血性视神经病变的治疗进展

前部缺血性视神经病变(anterior ischemic optic neuropathy, AION)是一种急性的视神经病变,多发生在50岁以上人群中,常导致急性无痛性视力丧失。其中,非动脉炎性前部缺血性视神经病变(non-arteritis anterior ischemic optic neuropathy,NAION)是最常见的类型,也是导致中老年人失明或严重视力障碍的主要原因之一。但目前,由于对本病发生机制认识不充分,临床上尚缺乏疗效确切的治疗方法。因此,寻找规范、有效的治疗方法显得尤为重要,以期达到控制病情发展进而减少致盲的临床效果。     

血清孕酮含量与前部缺血性视神经病变的相关性研究

目的通过检测血清孕酮含量,了解孕酮与前部缺血性视神经病变发病的相关性。方法收集前部缺血性视神经病变患者32例32眼为病变组,选取同期非缺血性视神经病变患者30例30眼为对照组。ELISA方法检测2组患者血清孕酮的含量,并进行统计学分析。结果病变组血清孕酮的含量为(0.41±0.15)μg.L-1,明显低于正常对照组(1.13±0.12)μg.L-1,差异有统计学意义(P<0.05)。病变组血清孕酮含量与视力的相关分析示,2者正相关(r=0.808,P<0.05),表明血清孕酮含量越低,视力损害越重。结论前部缺血性视神经病变患者血清中孕酮含量减少,对视神经的保护作用减弱,可能是缺血性视神经病变的主要发病机制之一。     

剔络化瘀养血明目法对早期非动脉炎性前部缺血性视神经病变患者视功能的影响

目的 探讨剔络化瘀养血明目法对早期非动脉炎性前部缺血性视神经病变患者视功能的影响.方法 回顾性分析2012年5月至2014年5月在我院住院部经剔络化瘀养血明目法治疗的早期非动脉炎性前部缺血性视神经病变患者21例(24眼).经归元剔络化瘀方、改善微循环类药物、营养神经类药物治疗2个疗程.观察治疗前后最佳矫正视力、视野的变化.结果 早期非动脉炎性前部缺血性视神经病变患者经剔络化瘀养血明目法治疗2个疗程后,视力提高0.18±0.24,较治疗前差异有显著统计学意义(P＜0.01);视野敏感度提高(2.34±3.65)dB,较治疗前差异有统计学意义(P＜0.05);视野缺损降低(-2.26±3.81)dB,较治疗前差异无统计学意义(P＞0.05).结论 剔络化瘀养血明目法能有效改善早期非动脉炎性前部缺血性视神经病变患者的视功能.     

间充质干细胞源性外泌体治疗干眼的研究进展

外泌体是一种细胞外囊泡,通过生物分子传递改变受体细胞的生化特性,并在细胞通讯中发挥作用。其中,间充质干细胞源性外泌体(MSC-Exos)是由间充质干细胞分泌的双层脂质囊泡,具有与间充质干细胞(MSCs)相似的功能,并携带蛋白质、脂质和核酸等生物活性物质,可作为细胞间通讯的媒介参与免疫调节、组织损伤修复和促进血管生成等多种重要生理过程,近年来在治疗免疫炎性疾病、缺血性疾病等相关领域成为研究的热点。本文从MSC-Exos的生物学功能出发,针对干眼不同发病机制如炎症反应、神经及组织修复等,阐述其治疗干眼的可能机制,以期为MSC-Exos在干眼治疗中的应用奠定基础,并为未来的临床应用提供参考依据。     

前部缺血性视神经病变的回顾分析

目的:掌握前部缺血性视神经病变的临床检查、诊断、治疗方法,挽救视功能。方法:回顾性分析32例缺血性视神经病变患者的临床检查治疗过程,观察治疗前后的视力变化、视野变化、OCT、眼底荧光血管造影结果等。结果:32例前部缺血性视神经病变病例中,通过控制全身疾病,局部激素治疗,扩张血管药物促循环,营养神经治疗,大部分病例视力有所提高,视盘水肿减轻,视野不同程度扩大,患眼OCT示:盘周神经纤维层变薄。结论:前部缺血性视神经病变的正确诊断,及时系统的治疗,可有效提高视力,改善视盘缺血状态,扩大视野、提高视敏度。     

外泌体在眼底疾病发病及治疗中的作用

外泌体是细胞内的多囊泡体通过与细胞质膜融合后主动分泌到细胞外的小囊泡。外泌体内含有多种活性物质,其在细胞间通讯、疾病进展及作为生物标记物方面的作用已渐被眼底疾病的学者关注。研究显示外泌体参与了湿性年龄相关性黄斑变性病理过程,而间充质干细胞外泌体能够降低湿性年龄相关性黄斑变性患者的血管内皮生长因子转录和翻译;在大鼠糖尿病性视网膜病变血浆中研究发现含有IgG的外泌体可激活视网膜内的经典补体途径促进内皮损伤,应用含有miR-126间充质干细胞衍生的外泌体可限制内皮细胞损伤;在缺血性视网膜病变研究中骨髓间充质干细胞的外泌体可使缺血模型鼠视网膜功能恢复;玻璃体切除联合人脐带组织分离的间充质干细胞外泌体填塞对黄斑裂孔具有辅助治疗作用;视网膜脱离患者使用间充质干细胞分泌的外泌体可抑制光感受器细胞的凋亡;在葡萄膜黑色素瘤患者中外泌体标记物检测有希望成为葡萄膜黑色素瘤的早期诊断手段;在早产儿视网膜病变中小胶质细胞分泌的外泌体具有保护作用等。对外泌体系统的了解及其与眼底疾病中的信号传递机制及疾病转归过程的认识,对优化眼底疾病防治具有重要意义。（国际眼科纵览,2020, 45：442-448）     

Ischaemic optic neuropathy

Ischaemic optic neuropathy is of two types: anterior (AION) and posterior (PION), the first involving the optic nerve head (ONH) and the second, the rest of the optic nerve. Pathogenetically AION and PION are very different diseases. AION represents an acute ischaemic disorder of the ONH supplied by the posterior ciliary artery (PCA), while PION has no specific location in the posterior part of the optic nerve and does not represent an ischaemic disorder of any definite artery. The most important step towards a logical understanding of the underlying causes, clinical features, pathogenesis and rational management of AION, is to understand the basic scientific issues involved; these are discussed in some detail. AION clinically is of two types: (1) that due to giant cell arteritis (arteritic AION: A-AION) and (2) non-arteritic AION (NA-AION). NA-AION, the more common of the two, is one of the most prevalent and visually crippling diseases in the middle-aged and elderly, and is potentially bilateral. NA-AION is a multifactorial disease, with many risk factors collectively contributing to its development. Although there is no known treatment for NA-AION, reduction of risk factors is important in decreasing chances of involvement of the second eye and of further episodes. Our studies have suggested that nocturnal arterial hypotension is an important risk factor for the development and progression of NA-AION. The role of nocturnal arterial hypotension in the pathogenesis of NA-AION and management of nocturnal hypotension is discussed. Potent antihypertensive drugs, when used aggressively and/or given at bedtime, are emerging as an important risk factor for nocturnal hypotension, and there is some evidence that NA-AION may be occurring as an iatrogenic disease in some individuals. A-AION, by contrast, is an ocular emergency and requires immediate treatment with systemic corticosteroids to prevent further visual loss. The clinical parameters which help to differentiate the two types of AION, and their respective management are discussed.     

Anterior ischemic optic neuropathy. VII. Incidence of bilaterality and various influencing factors

A prospective study was conducted in 438 patients with anterior ischemic optic neuropathy (AION). There were 388 patients with nonarteritic AION and 50 with arteritic AION. The risk of bilaterality in patients with arteritic AION was found to be 1.9 times the risk in patients with nonarteritic AION (P = 0.0118). The cumulative incidence curve, considering the time taken to develop bilateral AION for nonarteritic cases was significantly (P = 0.0103) different from that for arteritic cases. The estimated 25th-percentile time to development of bilateral AION was much shorter in patients with arteritic AION (0.4 month) than in those with nonarteritic AION (32.4 months). In arteritic AION, unilateral as well as bilateral AION had almost invariably developed before systemic steroid therapy was started and not after, indicating that this therapy is effective in preventing the development of AION in giant cell arteritis. In nonarteritic AION, the risk of bilaterality was significantly greater in men (P = 0.0113) and in young (less than 45 years old) patients with diabetes (P = 0.0245), with no significant difference attributable to the other age groups or other associated systemic diseases. In this study, it was found that young diabetic men have a risk of AION developing in the second eye that is 1.56 times the risk in young diabetic women, 2.56 times the risk in women who either are nondiabetic or are not young, and 1.64 times the risk in both older men and nondiabetic men.     

Treatment of anterior ischemic optic neuropathy: Clues from the bench

Anterior ischemic optic neuropathy (AION) is due to optic nerve head ischemia, and there is currently no effective treatment. Age is a significant risk factor for both arteritic and nonarteritic AION (NAION), although we do not fully understand the changes that occur in aging that lead to selective vulnerability of the optic nerve head. Arteritic AION, which is most often seen in the setting of giant cell arteritis, is caused by vasculitis and thromboembolism of the ophthalmic circulation leading to impaired perfusion of the short posterior ciliary artery and infarction of the optic nerve head. More commonly, AION is nonarteritic, and vision loss is typically altitudinal and noted most commonly upon awakening. NAION has been associated with a variety of risk factors, including disc-at-risk, vascular risk factors including diabetes, vasospasm and impaired autoregulation, nocturnal hypotension, and sleep apnea. This review summarizes the clinical presentation of non-arteritic AION and arteritic AION associated with giant cell arteritis and the current and future treatment approaches for human NAION based on lessons from photochemical thrombosis models of NAION.     

Acute anterior ischemic optic neuropathy in the course of optic nerve drusen

Authors present the case of 48 years old male with acute anterior ischemic optic neuropathy (AION) in presence of optic nerve drusen. AION occurred in both eyes, but not at the same time. Diagnosis was made on the basis of laboratory tests, ultrasonographic examination and fluorescein angiography. In the course of treatment improvement of visual acuity was achieved , but concentric constriction of visual field remained. As no effective treatment of non vascular AION was proposed so far, major stress should be put on elimination of its vascular risk factors.     

前部缺血性视神经病变患者药物改善异常血流变对中心视力恢复的影响

目的 观察药物对缺血性视神经病变患者血流变异常指标改变后对患者中心视力恢复的影响。方法 对105例缺血性视神经病变患者依据血流变异常选择不同药物治疗，联合普通药物、降纤酶、藻酸双酯钠等改善血液流变治疗，并以未行血流变检测和血流变改善药物治疗的60例缺血性视神经病变患者的中心视力恢复情况进行对照分析。结果 105例缺血性视神经病变患者血流变异常指标经不同药物联合治疗后，血流变各项异常指标均有明显改善。改善血流变指标治疗组患者视力恢复明显优于未经改善血流变指标治疗组（P＜0．05）。结论 降低血液粘稠度，采用不同药物改善血流变的异常指标、对于缺血性视神经病变患者视力的恢复具有重要意义。     

复方樟柳碱联合后Tenon囊下注射曲安奈德治疗前部缺血性视神经病变

目的:观察复方樟柳碱联合后Tenon囊下注射曲安奈德治疗前部缺血性视神经病变的疗效。方法:临床确诊的前部缺血性视神经病变患者58例60眼随机分为两组,其中29例30眼接受复方樟柳碱侧颞浅动脉旁注射联合曲安奈德20mg后Tenon囊下注射(治疗组);另外29例30眼采用复方樟柳碱侧颞浅动脉旁注射治疗(对照组);均以15d为1个疗程。两组患者用药后每天观察视力变化及视乳头水肿消退情况,治疗前有视野者复查视野。结果:治疗15d后,两组视力,视野及视乳头水肿情况均有不同程度改善,治疗组视力提高程度明显高于对照组,两组间差异有统计学意义(χ2=17.8,P<0.01);治疗组有视野检查的14眼中治疗后好转12眼(86%),2眼无变化(14%);对照组有视野检查的13眼中治疗后视野好转4眼(31%),9眼无变化(69%),两组视野变化比较差异有统计学意义(χ2=8.68,P<0.05)。结论:复方樟柳碱联合曲安奈德治疗AION优于单纯复方樟柳碱治疗。     

前部缺血性视神经病变患者治疗前后多焦视觉诱发电位检测结果分析

目的 观察前部缺血性视神经病变(AION)治疗前后多焦视觉诱发电位(mfVEP)的检查结果,初步探讨其临床应用意义.方法 对AION患者90例90只眼进行mfVEP检测,分析mfVEP的二阶反应,将反应分上、下半侧视野,及鼻上、鼻下、颞卜、颞下4个象限视野;分析各反应总和波,对各区域进行比较.观察AION眼与对侧眼及AION眼治疗前后各部分的波形特征.结果 治疗前AION眼病变受累区域mfVEP P波振幅及潜伏期分别为0.198±0.033、100.197±7.354,对侧眼相应区域分别为0.271±0.024、98.567±6.794,两者比较差异均有统计学意义(t=16.556,18.330;P＜0.01).治疗后AION眼病变区域P波振幅及潜伏期分别为0.229±0.016、100.104±10.603,与治疗前相比,差异均有统计学意义(t=7.622,5.501;P＜0.01);与对侧眼相比差异均有统计学意义(t=13.649,8.858;P＜0.01).结论 mfVEP P波振幅及潜伏期能够准确反映AION患眼治疗前后局部视神经损害及恢复情况,具有良好的可重复性.可以作为AION诊断及检测预后的新方法.     

苦碟子注射液治疗前部缺血性视神经病变的疗效观察

目的:观察苦碟子注射液治疗前部缺血性视神经病变(an-terior ischemic optic neuropathy,AION)的疗效。方法:临床确诊的AION患者32例32眼,其中16例16眼接受苦碟子注射液(沈阳双鼎制药有限公司)20mL静脉滴注治疗(治疗组);另外16例16眼接受丹参注射液(正大青春宝药业有限公司)20mL静脉滴注治疗(对照组)。均以15d为1个疗程。两组患者用药后每天观察视力、眼底变化,治疗前后均予视野检查。结果:治疗组视力提高程度明显好于对照组,两组间差异有统计学意义(P<0.01);用药第3,7,15d,治疗组视力提高程度明显好于对照组,其差异有统计学意义(P<0.01;P<0.05;P<0.01);治疗组中,14眼治疗后视野好转(87.50%);2眼无变化(12.50%)。对照组中,7眼治疗后视野好转(43.75%);9眼无变化(56.25%)。两组视野变化的差异比较有统计学意义(P<0.01)。结论:苦碟子注射液治疗AION安全有效。     

Functional rescue of experimental ischemic optic neuropathy with αB-crystallin

Purpose

Anterior ischemic optic neuropathy (AION) is an important cause of acute vision loss in adults, and there is no effective treatment. We studied early changes following experimental AION and tested the benefit of a potential treatment.

Materials and Methods

We induced experimental AION in adult mice and tested the effects of short-term (daily for 3 days) and long-term (every other day for 3 weeks) αB-crystallin (αBC) treatment using histological and serial intracranial flash visual evoked potential recordings.

Results

One day after experimental AION, there was swelling at the optic nerve (ON) head and increased expression of αBC, a small heat shock protein important in ischemia and inflammation. This upregulation coincided with microglial and astrocytic activation. Our hypothesis was that αBC may be part of the endogenous protective mechanism against injury, thus we tested the effects of αBC on experimental AION. Daily intraveneous or intravitreal αBC injections did not improve visual evoked potential amplitude or latency at days 1–2. However, αBC treatment decreased swelling and dampened the microglial and astrocytic activation on day 3. Longer treatment with intravenous αBC led to acceleration of visual evoked potential latency over 3 weeks, without improving amplitude. This latency acceleration did not correlate with increased retinal ganglion cell survival but did correlate with complete rescue of the ON oligodendrocytes, which are important for myelination.

Conclusions

We identified αBC as an early marker following experimental AION. Treatment with αBC enhanced this endogenous, post-ischemic response by decreasing microglial activation and promoting ON oligodendrocyte survival.     

Functional and cellular responses in a novel rodent model of anterior ischemic optic neuropathy

PURPOSE. Anterior ischemic optic neuropathy (AION) is caused by sudden loss of vascular supply to retinal ganglion cell (RGC) axons in the anterior portion of the optic nerve and is a major cause of optic nerve dysfunction. There has been no easily obtainable animal model of this disorder. The current study was conducted to design a novel model of rodent AION (rAION), to enable more detailed study of this disease. METHODS. A novel rodent photoembolic stroke model was developed that is directly analogous to human AION. Using histologic, electrophysiological, molecular- and cell biological methods, the early changes associated with isolated RGC axonal ischemia were characterized. RESULTS. Functional (electrophysiological) changes occurred in RGCs within 1 day after rAION, with a loss of visual evoked potential (VEP) amplitude that persisted in the long term. The retinal gene expression pattern rapidly changed after rAION induction, with an early (<1 day) initial induction of c-Fos mRNA, and loss of RGC-specific gene expression. RGC-specific protein expression declined 2 days after detectable mRNA level changes, and immunostaining suggested that multiple retinal layers react to isolated RGC axonal ischemia. CONCLUSIONS. rAION rapidly results in electrophysiological and histologic changes similar to clinical AION, with reactive responses in primary and supporting neuronal cell layers. The rAION model can enable a detailed analysis of the individual retinal and optic nerve changes that occur after optic nerve stroke, which may be useful in determining possible therapeutic interventions for this disorder.