青光眼神经保护：现在与未来

目的：回顾至今为止,神经保护研究在青光眼治疗的进展,以及相应的神经保护药物。 数据来源：本研究的数据来源于PubMed and Google Scholar databases 中至今10年内英文文章,搜索的关键词包括glaucoma, neuroprotection, and retinal ganglion cell,同时包括一些重要的旧的英文文章。 研究的选择: 选择关于青光眼神经保护的研究文章及综诉文章,同时上述文章中提到的一些重要的参考文献也被引用。 结果：降低眼压是目前唯一证实有效的青光眼治疗手段,但是越来越多的研究表明青光眼中视网膜神经节细胞丢失的机制是多方面的,包括神经营养因子剥夺,神经兴奋毒性,氧化应激损伤,线粒体功能的障碍,炎症及自主免疫的异常,调控凋亡基因的表达异常,血流的异常,细胞内蛋白质的错误折叠,针对各种损伤的机制都有各自的神经保护剂。同时针对轴突运输障碍,突触连接障碍,胶质细胞以及干细胞的应用的研究将是未来比较有前景的青光眼神经保护方面的研究。 结论：青光眼神经保护方面的研究需要更多的突破,未来对于青光眼发病机制的进一步认识将为青光眼神经保护提供理论依据。而建立一个更加有效的药物评估系统将有利于该方面的发展。     

Magnetic resonance in studies of glaucoma

Glaucoma is the second leading cause of blindness. It affects retinal ganglion cells and the optic nerve. However, there is emerging evidence that glaucoma also affects other components of the visual pathway and visual cortex. There is a need to employ new methods of in vivo brain evaluation to characterize these changes. Magnetic resonance (MR) techniques are well suited for this purpose. We review data on the MR evaluation of the visual pathway and the use of MR techniques in the study of glaucoma, both in humans and in animal models. These studies demonstrated decreases in optic nerve diameter, localized white matter loss and decrease in visual cortex density. Studies on rats employing manganese-enhanced MRI showed that axonal transport in the optic nerve is affected. Diffusion tensor MRI revealed signs of degeneration of the optic pathway. Functional MRI showed decreased response of the visual cortex after stimulation of the glaucomatous eye. Magnetic resonance spectroscopy demonstrated changes in metabolite levels in the visual cortex in a rat model of glaucoma, although not in glaucoma patients. Further applications of MR techniques in studies of glaucomatous brains are indicated.     

Cop 1对实验性高眼压性青光眼视神经的保护作用

目的 观察Copolymer 1（Cop 1）对大鼠高眼压模型视神经的保护作用,为Cop 1在抗青光眼视神经萎缩的临床应用提供实验室依据。方法 将30只成年Wistar大鼠用Shareef-Sharma法制作双眼高眼压模型,在眼压升高的第3周,在Cop 1模型组（n=15）大鼠的后脚皮内注射100 μg Cop 1和等体积的Freund 完全佐剂（CFA）混合乳化液;在模型对照组（n=15）大鼠后脚皮内注射等体积的PBS和CFA混合乳化液,6 d后用Fluorogold进行视网膜神经节细胞（RGC）逆行性染色,1 d后取出视网膜,比较两组RGC密度的差异。另取6只正常大鼠（未做高眼压模型）作空白对照组。结果 Cop 1模型组视神经和视网膜切片的HE染色显示视神经大量淋巴细胞聚集,Cop 1模型组和模型对照组RGC的损失率分别为10.24%±3.75%和29.00%±6.92%;Cop 1模型组的RCG密度显著高于模型对照组（P＜0.05）,但与空白对照组差异无统计学意义（P>0.05）。结论 Cop 1皮内注射能减少高眼压对RGC的损害。     

孕酮对慢性高眼压模型大鼠视网膜神经节细胞的保护作用

目的：建立大鼠慢性高眼压模型，检测孕酮对高眼压下大鼠视网膜神经节细胞的保护作用。方法：通过烧灼3条巩膜上静脉制作慢性高眼压动物模型，此模型按腹腔注射不同浓度的孕酮而分为高、中、低浓度孕酮注射组及空白对照组，左眼为模型眼，右眼为自身对照眼，3个月后处死动物，取眼球制石蜡切片，行HE染色、Thy-1.1免疫组化染色及TUNEL原位凋亡检测。结果：各组模型眼比较，高浓度孕酮注射组视网膜神经节细胞数多于低、中浓度孕酮注射组及空白对照组（P<0.05），且TUNEL阳性细胞数也少于低、中浓度孕酮注射组及空白组(P<0.05)。结论：孕酮对慢性高眼压模型大鼠的视网膜神经节细胞有保护作用，并且此保护作用与孕酮的浓度有关。     

Role of mitochondria in the pathogenesis and treatment of glaucoma

Objective To gain insight into the potential mechanism of mitochondria dysfunction in pathogenesis, progression and therapeutic management of glaucoma. Data sources The data used in this review were mainly published in English from 2000 to present obtained from PubMed. The search terms were ＂mitochondria＂, ＂glaucoma＂ and ＂trabecular meshwork＂ or ＂retinal ganglion cells＂. Study selection Articles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed. Results Mitochondrial dysfunction or injury was demonstrated in different eye tissue of glaucoma. A variety of potential injuries （light, toxic materials, oxidative injury, mechanical stress, aging, etc.） and the inherent DNA defects are deemed to cause mitochondrial structural and functional destruction in trabecular meshwork cells, retinal ganglion cells, etc. of glaucoma. In addition, various new experimental and therapeutic interventions were used to preserve mitochondrial function, which may be useful for protecting against optic nerve degeneration or reducing the death of retinal ganglion cells in glaucoma. Conclusions Mitochondria play an important role in the pathogenesis of glaucoma, various strategies targeting mitochondrial protection might provide a promising way to delay the onset of glaucoma or protect RGCs against glaucomatous damage.     

Advances in optic nerve regeneration and neuroprotection strategies

The most common irreversible blindness diseases are age-related macular degeneration,glaucoma,and diabetic retinopathy which involve the optic nerve or retina.These diseases share a common condition of causing blindness-progressive neural cells loss of retina (photoreceptor cells,retinal ganglion cells (RGCs)).Although many advances in the treatment for these diseases have been achieved in recent years,the visual function often cannot be reversed.To improve the visual outcomes,the retinal neuron cells must be rescued.Optic nerve diseases including glaucoma were mostly studied for the effort to rescue the injured neurons and regenerate the neuron axons.     

多聚物-1反应性T细胞对高眼压大鼠视网膜神经节细胞的保护机制

 目的 探讨多聚物-1（copolymer-1,Cop-1）反应性T细胞对高眼压大鼠视网膜神经节细胞（retinal ganglion cells,RGCs）的保护机制。方法 大鼠后肢足垫注入0.2mgCop-1或磷酸盐缓冲溶液（phosphate buffered solution,PBS）后10d,取出腹股沟淋巴结,培养Cop-1反应性T细胞（TCop-1）或PBS对照组T细胞（TPBS）,用逆转录聚合酶链反应测定gamma干扰素（interferon –gamma,γ-IFN）和IL-4 mRNA的表达水平,从而分析培养的T细胞亚型;39只高眼压大鼠随机分为2组,1组（n=19）腹膜内注射TCop-1,另1组 (n=20)注入TPBS作为对照,21d后观察RGCs的存活情况;用ELISA法测定T细胞上清液中脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）的分泌量。结果 免疫后21d,Cop-1组RGCs存活数目较PBS组多（t=8.0204,P<0.01）,TCop-1组gamma干扰素（interferon –gamma,γ-IFN）mRNA表达水平较PBS组高,而IL-4在两组间的表达差别无统计学意义。TCop-1在Cop-1刺激后脑源性神经营养因子分泌量为（3385.42±836.33）pg/mL,单纯TCop-1分泌量为（1026.24±135.10）pg/mL,而TPBS分泌量为（19.87±71.20）pg/mL。前者分泌量远大于后两者（F=175.66,P<0.01,P<0.01,单因素方差分析,Bonferroi）。结论 Cop-1反应性Th1细胞是发挥视神经保护作用的重要细胞,保护机制之一可能通过TCop-1在局部分泌BDNF来实现。     

BDNF对实验性急性高眼压兔眼视网膜神经节细胞的保护作用

目的探讨脑源性神经营养因子(Brain-Derived Neurotrophic Factor,BDNF)对实验性急性高眼压(Hyper-intraocular Pressure,HIOP)兔眼视网膜神经节细胞(RGCs)的保护作用。方法将16只健康中华大耳白兔随机等分为实验组(BDNF)和空白对照(PBS)组,用前房灌注法建立右眼实验性急性HIOP模型,左眼作为正常对照。于灌注前,在BDNF组和PBS组右眼玻璃体腔内分别注射BDNF 3.75μg或等量0.1 mol/L磷酸缓冲液(PBS),第14d让实验兔安乐致死。实验兔致死前48 h以辣根过氧化物酶(HRP)逆向标记双眼RGCs,视网膜铺片后以3,3’,5,5’-四甲基联苯胺(TMB)法呈色,计数下半视网膜距视盘边缘2 mm、4 mm、6 mm处的RGCs密度。结果距视盘边缘2 mm4、mm、6 mm处,正常对照组的RGCs密度分别为1619±377个/mm2、771±232个/mm2、358±122个/mm2;BDNF组的RGCs密度为1304±246、669±283、283±93个/mm2,距视盘边缘2 mm6、mm处,BDNF组与正常对照组RGCs密度的差异有非常显著性意义(均P<0.01);PBS组的RGCs密度分别为1002±410个/mm2、627±211个/mm2、264±107个/mm2,与正常对照组RGCs密度的差异均有显著性意义(均P<0.05);距视盘边缘2 mm处,BDNF组与PBS组的RGCs密度的差异有显著性意义(P<0.05)。结论BDNF可提高实验性急性高眼压兔眼RGCs的存活率,对RGCs具有保护作用。     

线粒体在青光眼发病及治疗中的研究进展

Mitochondria are recognized as central players in the life and death of cells. Increasingly, studies are focused on the deep-seated relationship between mitochondrial pathologic mechanism and glaucoma. A variety of potential injuries (light, toxic materials, oxidative injury, mechanical stress, aging, etc.) and the inherent DNA defects are deemed to cause mitochondrial structural and functional destruction of trabecular meshwork cells, retinal ganglion cells, etc. in glaucoma. In addition, various new experimental and therapeutic interventions were used to preserve mitochondrial function, which may be useful for protecting against optic nerve degeneration or reducing the death of retinal ganglion cells in glaucoma. This review aims to gain insight into the potential mechanism of mitochondria dysfunction in pathogenesis, progression and therapeutic management of glaucoma in recent years.     

Neovascular glaucoma: challenges we have to face

Neovascular glaucoma （NVG） is a blinding, intractable disease, which is difficult to manage. It is referred to as an ＂end-stage＂ ocular disease. Conventional treatments for extremely uncontrolled NVG cases include retinal cryotherapy or enucleation. Major advancements in the diagnosis and the treatment of NVG, such as glaucoma drainage implant surgery and anti-vascular endothelial growth factor （anti-VEGF） treatment, have led to a new era in the management of this condition. However, many challenges still remain to be overcome.     

Preliminary studies on the application of retinal thickness analyzer in the diagnosis of glaucoma

The pathological basis of the glaucomatousdamage includes the injury of ganglion cells and theloss of the retinal nerve fibers[1] ,presenting thechange in retinal thickness. 50 % of the ganglioncells locate at the region of 4.5mm from the centralfovea of macula[2 ] . The measurement of the retinalthickness at the posterior pole across the macula willbe beneficial to the determination of the damage tothe ganglion cells and the nerve fibers,so as to diag-nose glaucoma early.Retinal thickness ana…     

猪视网膜神经节细胞的培养及超微结构

目的：建立视网膜神经节细胞（retinal ganglion cells,RGCs)的体外培养方法,并研究视网膜不同类型神经细胞之间的相互作用,为RGCs的体外实验研究奠定基础。方法：进行猪视网膜细胞混合体外培养和神经节细胞的纯化培养,观察神经节细胞生长状态及轴突生长情况,研究视网膜不同类型神经细胞之间的相互作用。结果：视网膜细胞混合培养时,神经节细胞生长良好,纯化后的神经节细胞间连接减弱,细胞存活时间缩短。结论：视网膜细胞混合培养有利于神经节细胞的贴壁和生长。     

Diagnostic capability of Fourier-Domain optical coherence tomography in early primary open angle glaucoma

Background Optical coherence tomography （OCT） is a high resolution noncontact imaging modality which can quantitatively detect the optic disc and retinal structure.This study was designed to evaluate the diagnostic capability of parameters of the optic disc, retinal nerve fiber layer thickness, and ganglion cell complex （GCC） using a new technology called Fourier-domain OCT （FD-OCT） for early primary open angle glaucoma （POAG） patients.Methods Two groups of patients, early perimetric damage POAG and normal subjects were included in this observational cross-sectional study.All patients underwent FD-OCT and visual field examination in addition to full ophthalmic examinations.Receiver operating characteristic curves （ROC） were studied for all parameters.The sensitivity and specificity for distinguishing between normal and early glaucomatous eyes, the areas under the receiver operating characteristic curves （AROC） and positive, negative likelihood ratios were evaluated for all the single parameters and selected combined parameters using arbitrary cutoffs.Results Thirty-four eyes of 34 early POAG patients and 42 eyes of 42 normal subjects were analyzed.Cup/disc （C/D）vertical ratio presented the best sensitivity and positive likelihood ratio for selected specificities （95% and 85%） which were 79.4% and 88.2%, 33.4 and 7.4, respectively.Among all single parameters, the C/D vertical ratio demonstrated the highest AROC which was at 0.930.The average thickness of circumpapillary RNFL on 3.45 mm showed the highest AROC among all of the peripapillary RNFL parameters.The sensitivity at selected specificity and AROC of GCC were not as high as C/D vertical ratio and RNFL AT on 3.45 mm.When the C/D vertical ratio, RNFL AT on 3.45 mm, and rim area were combined using a logistical diagnostic model, the AROC was raised to 0.949 but not significantly different from the top single parameter, C/D vertical ratio.Conclusions The key parameters obtained by FD-OCT were able to show the significant differences of optic discs,thickness of RNFL and GCC between POAG patients and normal subjects.According to sensitivity, specificity, likelihood ratio and AROC, the top three parameters from FD-OCT for early diagnosis of POAG were C/D vertical ratio, RNFL AT on 3.45 mm, and the rim area.     

视网膜神经保护因子的研究进展

各种原因造成的视网膜完全或部分缺血，可导致视网膜节细胞（RGC）的死亡和神经纤维数量的减少，这是造成视功能不可逆损害的主要病理基础。近几年大量的研究表明，许多蛋白和因子对视网膜神经元的保护起重要的作用，如：热激蛋白（HSP）、脑源性神经营养因子（BDNF）、肝细胞生长因子（HGF）等能减轻急性高眼压或急性视网膜缺血对RGC和视神经纤维所造成的损害，对神经元的保护起重要作用。本文对视网膜神经保护因子的研究进展简要作一综述。     

视神经损伤细胞凋亡与神经保护的实验研究进展

视神经损伤常导致视网膜神经节细胞的凋亡,其有关机制及如何抑制凋亡,从而保护损伤视神经的研究逐渐受到重视,相关体内、体外实验取得一定成果,本文加以阐述。     

青光眼与健康眼的视网膜血氧饱和度比较

目的 探讨青光眼患部的视网膜血氧饱和度变化。方法 选取2011 年5 月-2016 年3 月于四川省攀枝花市中心医院收治的的青光眼患者80 例共139 眼（观察组）和同期到该院接受检查的健康者80例共146 眼（对照组）,比较两组的视网膜血氧饱和度和视野指标,并进行相关性分析。结果 两组的视网膜静脉血氧饱和度比较无差异（P >0.05）。观察组的视网膜动脉血氧饱和度和动静脉血氧饱和度差值低于对照组（P <0.05）。观察组的平均视网膜光敏感度低于对照组,平均视野缺损度高于对照组（P <0.05）。动静脉血氧饱和度差值与平均视网膜光敏感度呈正相关（P <0.05）,与平均视野缺损度呈负相关（P <0.05）。结论 青光眼患部视网膜动脉血氧饱和度降低,视网膜静脉血氧饱和度无明显变化,且与视网膜光敏感度和视野缺损度密切相关。     

康柏西普玻璃体腔注射联合青光眼阀及全视网膜光凝治疗新生血管性青光眼

目的：探讨玻璃体腔注射康柏西普（conbercept）联合青光眼阀及全视网膜光凝治疗新生血管性青光眼的疗效和安全性。方法回顾分析我院2014年5—10月20例新生血管性青光眼患者行玻璃体腔注射康柏西普0．5 mg／0．05 ml）,待虹膜新生血管消退或萎缩后,行青光眼阀植入术和全视网膜光凝。其中8例联合白内障超声乳化＋人工晶体植入术。术后随访3 mo,观察视力、眼压和手术并发症等情况。结果玻璃体腔注射后3～7 d,18例新生血管全部消退。注射后患者眼压无特殊波动,植入青光眼阀及全视网膜光凝后,患者平均眼压由入院（60．55±9．89） mmHg,P＜0．05）降至出院（15．58±2．58） mmHg, P＜0．05）。随访3 mo后,视力提高和不变15眼,视力下降5眼。手术完全成功12眼,部分成功5眼,失败为3眼。结论玻璃体腔注射康柏西普后植入青光眼阀和进行全视网膜光凝治疗新生血管性青光眼是一种安全,有效的方法。