藏红花提取液对兔慢性高眼压视神经轴突数目的影响

目的探讨慢性高眼压后兔眼视神经轴突数目的变化情况及藏红花提取液对视神经轴突损伤的保护作用。方法将新西兰白兔20只随机分为对照组、高眼压组、治疗I组和治疗Ⅱ组，每组均为5只兔10眼。高眼压组和治疗Ⅰ、Ⅱ组兔眼前房注入3g ·L^-1复方卡波姆溶液制作成慢性高眼压模型。治疗Ⅰ、Ⅱ组兔每日耳缘静脉推注藏红花提取液。4周后利用图像分析系统对视神经轴突数目及所占面积百分比进行定量测定。结果正常对照组与高眼压组、治疗Ⅰ组轴突数目比较有统计学意义（P〈0．05）；治疗Ⅱ组与正常对照组轴突数目比较无统计学意义（P〉0．05）。结论慢性高眼压可导致视神经轴突数量明显减少，藏红花提取液可通过各种途径显著增加视神经轴突的存活率，对视神经起到一定的保护作用。[眼科新进展2007；27（3）：173-175]     

正常成年人与绝对期青光眼视神经轴突的定量微机图像分析研究

目的探讨绝对期青光眼视神经轴突损害的程度，以便说明绝对期青光眼视功能丧失的原因。方法对１０例猝死而生前健康的成年人１０只眼球及１０例１０只患绝对期青光眼眼球，用微机图像分析技术定量测定了其视神经轴突直径、轴突总数以及轴突数占视神经面积百分率。结果显示绝对期青光眼视神经轴突的上述各数值异于正常人，轴突直径明显增大，轴突总数明显减少，占视神经面积百分率明显降低，差异非常显著（Ｐ＜０．００１）。结论提示长时间的高眼压是造成青光眼视神经损害的重要原因之一。     

苯妥英钠对慢性高眼压兔视神经的保护作用

目的　观察苯妥英钠对慢性高眼压兔视网膜神经节细胞（ｒｅｔｉｎａｌｇａｎｇｌｉｏｎｃｅｌｌ,ＲＧＣ）及视神经的保护作用。方法　３０只新西兰白兔随机分为３组:高眼压组、高眼压治疗组与正常眼压组,每组１０只。每天高眼压治疗组给予苯妥英钠灌胃。高眼压造模成功后４周时摘除３组兔眼球标本分别做ＨＥ染色和ＴＵＮＥＬ标记,观察ＲＧＣ的细胞密度和凋亡细胞数量,用透射电子显微镜观察视网膜细胞凋亡情况。结果　节细胞层凋亡细胞:正常眼压组（０．４０±０．１５）×１０－２μｍ－２,高眼压组（３．４０±０．６２）×１０－２μｍ－２,高眼压治疗组（１．７５±０．２８）×１０－２ μｍ－２;内核层:正常眼压组（０．９５±０．２４）×１０－２ μｍ－２,高眼压组（１８．７０±２．４１）×１０－２μｍ－２,高眼压治疗组（８．７５±１．０３）×１０－２μｍ－２。高眼压组和高眼压治疗组与正常眼压组比较,ＲＧＣ密度减小、各层凋亡细胞数量增多（均为Ｐ＜０．０５）;高眼压治疗组与高眼压组比较,ＲＧＣ密度大、凋亡细胞数量少（均为Ｐ＜００５）。电镜下高眼压组与高眼压治疗组均观察到凋亡小体。结论　苯妥英钠对慢性高眼压ＲＧＣ和视神经有保护作用。     

LASIK手术时眼压波动对视神经轴突影响的实验研究

目的:定量观察LASIK手术时不同大小的负压吸引对兔视神经轴突的影响,以评估LASIK手术的安全性。方法:33只新西兰兔随机分为常规负压组、高负压组和超高负压组,分别采用不同大小的负压吸引,吸引阶段眼压分别升高至60mmHg、90mmHg和120mmHg,6w后取视神经标本,应用计算机图像分析进行视神经轴突计数。结果:超高负压组手术眼和对照眼视神经轴突数差异有统计学意义,P<0.01;另外两组手术眼与对照眼视神经轴突数差异无统计学意义,P>0.05。结论:在LASIK手术时,不宜采用过高的负压吸引,过高的负压吸引存在着潜在的危险性,瞬间的大幅度非生理性眼压波动可导致视神经轴突的不可逆损害。     

疏肝通窍法对青光眼视神经损害大鼠视网膜神经节细胞凋亡及视网膜、视神经超微结构的影响

目的：通过观察视网膜神经节细胞（RGCs）计数和视网膜、视神经超微结构及形态学变化,研究疏肝通窍法保护高眼压损害的视神经的作用机制,为开发保护青光眼视神经的有效中药方剂提供参考。方法：实验研究。以SD大鼠为实验动物,右眼前房注射复方卡波姆溶液建立慢性高眼压模型（90只）。将不同时间窗（1周、2周、3周）的慢性高眼压大鼠模型分别分为模型组（5只）、阴性对照组（5只）、阳性对照组（5只）、低剂量通窍明目4号治疗组（低剂量治疗组） （10 gkg-1d-1,5只）、中剂量治疗组（20 gkg-1d-1,5 只）和高剂量治疗组（40 gkg-1d-1,5 只）,以具有疏肝通窍作用的通窍明目4 号灌胃为干预手段,运用CMIAS系列数码医学图像分析系统观察RGCs计数,电镜观察视网膜、视神经超微结构,采用one-way ANOVA法和LSD法进行数据分析。结果：①RGCs计数：随着高眼压持续的时间延长,RGCs计数逐渐减少（F=87.67、29.69、33.38、38.03、33.67、23.36,P<0.001）,经药物治疗后,高眼压持续1周、2周和3周各组的高中剂量治疗组RGCs的存活量明显增加,与阴性对照组和阳性对照组比较差异均有统计学意义（P<0.001）。②模型组和阴性对照组视网膜结构排列紊乱,厚度变薄,空泡变性,细胞萎缩坏死,各治疗组视网膜的结构紊乱减轻,各层厚度略增加,空泡变性减少,细胞萎缩程度减轻。③模型组和阴性对照组视神经轴突排列紊乱,密度降低,微丝溶解,空泡样变,细胞器肿胀破坏,髓鞘变性,各治疗组视神经髓鞘的水肿程度减轻,髓索的变性有所修复,线粒体的水肿程度也减轻。结论：通窍明目4 号可以改善高眼压大鼠模型RGCs生存的微环境,保护未受损的细胞,修复轻度受损的RGCs,延缓或阻止部分受损细胞的下行性改变,减少高眼压大鼠模型RGCs的凋亡。疏肝通窍法对青光眼视神经损害具有保护作用。     

慢性高眼压大鼠外侧膝状体神经元的损伤

目的观察在持续高眼压状态下大鼠外侧膝状体（lateral geniculate nucleus．LGN）细胞结构的变化及其与视神经纤维丢失的关系。方法通过烧灼大鼠巩膜表层静脉诱导建立大鼠慢性高眼压模型，左眼为实验眼，右眼为对照眼，分别于2、4、6个月后经心脏灌注内固定取材，对两侧LGN及视神经进行形态学观察；通过突触素P38单克隆抗体免疫组化技术，利用计算机图像分析，对LGN视神经末梢突触分布情况进行检测。并对两侧LGN及视神经的观察结果进行比较。结果随高眼压持续时间的延长。大鼠左眼视神经轴突数目以及右侧LGN神经元大小、密度显著减小；LGN内突触素P38免疫反应阳性产物平均光密度值呈下降趋势；LGN神经元的损伤与视神经轴突数目及突触素光密度值显著相关。结论持续性眼压升高对大鼠LGN有明显损伤作用；高眼压大鼠LGN的损伤继发于视神经的损伤。     

兔视神经间接损伤病理学观察

目的　观察视神经间接损伤后病理学过程。方法　选用７２ 只兔（１４４ 只眼）制作视神经间接损伤动物模型,随机分为单纯致伤组和激素治疗组。动态行光镜和电镜观察,采用计算机行轴突计数。结果　视神经间接损伤后主要表现为水肿、髓鞘脱失、髓鞘再生和轴突的改变。激素治疗组的水肿较轻（Ｐ＜０－０１）,有髓纤维计数较多。结论　视神经发生间接损伤后主要改变是神经的水肿、脱髓鞘和轴突的变化。激素有一定的治疗作用。     

拉坦前列素和噻吗心安治疗开角型青光眼、高眼压症的对照研究

目的：观察Ｌａｔａｎｏｐｒｏｓｔ的降眼压效果及安全性。方法：采用随机分组对照组,０．００５％Ｌａｔａｎｏｐｒｏｓｔ每日一次或０．５％Ｔｉｍｏｌｏｌ（噻吗心安）每日２次,治疗原发性开角型青光眼、高眼压症和剥脱性青光眼,共１４例,疗程１２周,观察其眼压及不良反应。结果：Ｌａｔａｎｏｐｒｏｓｔ组和Ｔｉｍｏｌｏｌ组均可有效地降低眼压（Ｐ〈０．０１）,两组间眼压下降值没有差异。两组治疗前后不同时间点眼压下降     

超声微泡造影剂联合鼠神经生长因子对高眼压兔视神经损害的保护作用

目的　观察超声微泡造影剂联合鼠神经生长因子（ｍｏｕｓｅｎｅｒｖｅｇｒｏｗｔｈｆａｃｔｏｒ,ｍＮＧＦ）对高眼压兔视神经损害的保护作用。方法　新西兰大白兔４０只,随机分为５组（每组８只）。空白对照组（Ａ组）、高眼压模型组（Ｂ组）、高眼压模型＋玻璃体内注射ｍＮＧＦ组（Ｃ组）、高眼压模型＋玻璃体内注射ｍＮＧＦ联合超声组（Ｄ组）、高眼压模型＋玻璃体内注射ｍＮＧＦ联合超声微泡组（Ｅ组）。行闪光视觉诱发电位（ｆｌａｓｈｖｉｓｕａｌｅｖｏｋｅｄｐｏｔｅｎｔｉａｌ,Ｆ-ＶＥＰ）检测,记录Ｐ１００波潜伏期及振幅;取各组兔视网膜行病理形态学观察和透射电镜观察兔视神经超微结构。结果　Ｂ组眼压在造模后１周、２周、４周分别为（３３．４±２．８）ｍｍＨｇ（１ｋＰａ＝７．５ｍｍＨｇ）、（３４．１±２．５）ｍｍＨｇ和（３４．８±２．２）ｍｍＨｇ,与Ａ组眼压（１３．６±１．８）ｍｍＨｇ、（１３．４±１．７）ｍｍＨｇ和（１３．３±１．４）ｍｍＨｇ相比差异有显著统计学意义（Ｐ＝０．０００）。Ｂ组的Ｐ１００潜伏期（１２５．００±１８．７０）ｍｓ和振幅（５．５０±３．０３）ｎＶ较Ａ组的Ｐ１００潜伏期（４６．２０±６．９０）ｍｓ和振幅（１５．９０±２．４８）ｎＶ明显延长和降低,差异有统计学意义（Ｐ＜０．０５）;Ｅ组的Ｐ１００潜伏期（６３．８０±８．３５）ｍｓ和振幅（１１．３７±２．８４）ｎＶ较Ｂ、Ｃ、Ｄ组明显缩短和升高,差异有统计学意义（Ｐ＜０．０５）。Ｂ组视网膜神经节细胞（ｒｅｔｉｎａｌｇａｎｇｌｉｏｎｃｅｌｌｓ,ＲＧＣ）计数（１４．９７±１．３０）个明显少于Ａ组（２６．０４±０．７０）个,差异有统计学意义（Ｐ＜０．０５）;Ｅ组ＲＧＣ计数（２３．９７±０．９０）个明显高于Ｂ、Ｃ、Ｄ组,但仍低于Ａ组,差异有统计学意义（Ｐ＜０．０５）。Ｅ组兔视网膜各层结构较Ｂ、Ｃ、Ｄ组完整,分层较清晰。Ｅ组兔视神经髓鞘结构尚完整,轴突内微管、微丝结构可见,较Ｂ、Ｃ、Ｄ组视神经超微结构明显改善。结论　超声微泡造影剂与鼠神经生长因子联合使用可增强鼠神经生长因子对高眼压兔视神经损害的保护作用。     

球后植入微泵缓释内皮素-1诱导的视盘慢性缺血模型

目的植入微泵缓释内皮素1(endothelin1,ET1)至猫眼球后视神经近球壁处,诱导慢性视盘缺血动物模型,研究慢性缺血对视神经的影响。方法成年猫7只,4只雌性,3只雄性。右眼为实验眼,左眼为对照眼。实验眼用2.2×10-5MET1,对照眼用相应赋形剂。术前进行眼部检查、眼压测量、海德堡视网膜断层扫描仪(heidelbergretinaltomography,HRT)分析视盘形态、海德堡视网膜血流仪(heidelbergretinalflowmetry,HRF)分析视盘筛板微循环及视网膜血管血流参数。术后2个月进行眼部检查,测量眼压,HRT、HRF分析同术前。摘除眼球取视神经标本,制成切片后进行视神经轴突计数分析。结果实验眼的基础、术后眼压比较,差异有显著性(P<0.05),对照眼的基础、术后眼压比较,差异无显著性;视盘HRT形态参数、视网膜血管血流指标术前、术后及两组间比较差异均无显著性;实验眼术后视盘筛板微循环指标较基础值降低,血流量降低31.91%,血流速降低61.22%,红细胞移动速率降低60.00%,对照眼差异无显著性;术后实验眼较对照眼视神经轴突数减少13.91%。结论微泵球后视神经近球壁处缓释2.2×10-5MET1(0.055μg/μl),可诱导视盘慢性缺血,实验眼术后的筛板微循环指标、视神经轴突计数均明显低于对照眼,而视网膜血管血流指标无影响。     

Characteristics of Optic Nerve Damage Induced by Chronic Intraocular Hypertension in Rat

Purpose:To set up the Sharma‘s chronic intraocular hypertension model and investigate the intraocular pressure (IOP) as well as the optic nerve damage of this model in rat.Methods :The operations of the chronic intraocular hypertension model were performed as described by Sharma in 60 male Lewis albino rats. IOP was measured using the TonoPen XL immediately after surgery and then at 5 day, 2 week or 4 week intervals. Cresyl violet staining of whole-mounted retinas was used to label retinal ganglion cells (RGCs),then RGCs were counted. Paraphenylenediamine (PPD) staining was performed in the semi-thin cross sections of optic nerve of rat, in order to know whether the axons of optic nerve were degenerated or not.Results:There were 47 rats with higher IOP after the episcleral veins cauterized in 60 rats. The ratio of elevated IOP was 78.3%. The IOPs were stable in 4 weeks. After cresyl violet staining, the RGCs loss was 11.0% and 11.3% was found in the central and peripheral retina respectively after 2 weeks of increased IOP. After 4 weeks of increased IOP, the loss of RGCs was 17% for the central retina and 24.6% for the peripheral retina. In the retinas without higher IOP, there was no loss of RGCs. PPD staining showed that optic nerve of rat with about 5.3% damage of axons located at the superior temporal region. Region of affected optic nerve 1 mm posterior to the globe by light microscope showed evidence of damaged axons with axonal swelling and myelin debris.Conclusion:Sharma‘s chronic intraocular hypertension model is a reproducible and effective glaucoma model, which mimics human glaucoma with chronically elevation IOP and induced RGCs loss and damage of optic nerve.     

Chronic experimental glaucoma in primates. II. Effect of extended intraocular pressure elevation on optic nerve head and axonal transport

Intraocular pressure (IOP) elevations lasting from 2 to 42 days were produced in 13 primate eyes by anterior chamber injections of autologous, fixed red blood cells. The retina, optic nerve head, and optic nerves were studied by electron microscopy, and ganglion cell rapid axonal transport was examined after IOP elevations for various durations. Transport of axonal material was blocked at the scleral lamina cribrosa by IOP elevations to 50 mm Hg. With IOP elevation for less than 1 week, return to normal IOP restored normal transport in some axons. However, in other axons IOP elevation for less than 1 week intiated ganglion cell degeneration. The process of cellular death involved a rapid ascending degeneration from nerve head to brain, followed 3 to 4 weeks later by descending degeneration of the ganglion cell body and its attached axon. Axons of the superior and inferior optic nerve head and nerve seem to be damaged more extensively than those in the nasal and temporal optic nerve. Two to four days after IOP elevation, axons of the superficial optic nerve head were swollen with accumulating axonal material, leading to histologic disk edema. In those eyes with IOP elevation longer than 1 week, the loss of anterior disk nerve fibers combined with posterior and lateral movement of the lamina cribrosa lead to an increase in optic disk cupping. Astrocytes and capillaries of the optic nerve head seem to tolerate elevated IOP well and were relatively spared.     

脑神经生长素治疗兔急性高眼压视神经损伤

目的 观察脑神经生长素(cranial nerve growthine,CNG)对兔眼急性高眼压视神经损伤的治疗作用。 方法 健康成年新西兰大耳白兔(体重2.5～3.0 kg)30只,随机分为5组,每组6只,一只眼前房内灌注生理盐水使眼压升高到50 mm Hg(1 mm Hg＝0.133 kPa),并维持6 h,另一只眼为自身对照眼。每组3只兔制成高眼压模型眼后肌肉注射CNG0.2 ml/d作为治疗组,其余3只兔为实验组。5组兔分别于制造模型眼后1、3、7、15、30 d处死。用辣根过氧化物酶(horserdish peroxidase,HRP)组织化学染色法和透射电镜技术观察CNG对急性高眼压视神经顺行轴浆运输和超微结构的影响,定量分析CNG的药物疗效。 结果 7 d后,治疗组HRP反应物积分光密度(39.79±2.29)较实验组(25.17±1.03)明显增多,差异有显著性意义(P＜0.01);治疗组视神经轴突变性较实验组轻,15 d后,部分轴突结构恢复正常,线粒体增多,30 d后,轴突结构基本正常。 结论 CNG可改善急性高压眼视神经轴浆运输状况,促进视神经结构的恢复。 (中华眼底病杂志,2000,16:88-90)     

Axonal transport and cytoskeletal changes in the laminar regions after elevated intraocular pressure

PURPOSE: To investigate the axonal cytoskeleton changes occurring in the prelaminar region, lamina cribrosa, and postlaminar region of the porcine optic nerve after an acute increase in intraocular pressure (IOP) and whether this corresponds with axonal transport abnormalities. METHODS: Six white Landrace pigs were used. The left eye IOP was elevated to 40 to 45 mm Hg for 6 hours, and the right eye IOP was maintained between 10 and 15 mm Hg. Rhodamine-beta-isothiocyanate (RITC) was injected into the vitreous of each eye at the beginning of the experiment, to study axonal transport. After euthanasia, optic nerves were removed and prepared for axonal transport and cytoskeleton studies. Antibodies to phosphorylated neurofilament heavy (NFHp), phosphorylation-independent neurofilament heavy (NFH), neurofilament light (NFL), neurofilament medium (NFM), microtubule, and microtubule-associated protein (MAP) were used to study the axonal cytoskeleton. Montages of confocal microscopy images were quantitatively analyzed to investigate simultaneous changes in optic nerve axonal transport and cytoskeletal proteins in the high-IOP and control eyes. RESULTS: Axonal transport of RITC was reduced in the prelaminar, lamina cribrosa, and proximal 400 mum of the postlaminar optic nerve regions in the high-IOP eye. NFHp, NFM, and NFH were significantly reduced in the prelaminar, lamina cribrosa, and proximal postlaminar regions in the high-IOP eye. No differences in NFL, MAP, and tubulin staining were detected. CONCLUSIONS: Elevated IOP induced both axonal transport and cytoskeleton changes in the optic nerve head. Changes to the cytoskeleton may contribute to the axonal transport abnormalities that occur in elevated IOP.     

High intraocular pressure-induced ischemia and reperfusion injury in the optic nerve and retina in rats

• Purpose: The purpose of this paper is to describe the damage caused to the retina and the axons of the optic nerve by acute ischemia-reperfusion injury and the extent to which optic nerve damage correlates with the duration if ischemia due to high intraocular pressure (IOP). • Methods: Acute ischemia in the retina and optic disc was induced in albino rats by increasing the IOP to 110 mmHg for a period of 45–120 min. Thereafter, the eyes were reperfused at normal IOP after 7 days. The retina and optic nerve were examined by light and electron microscopy, and morphometrical counts of the optic nerve axons were performed. • Results: After 45 min of ischemia, electron microscopic examination revealed swelling of mitochondria and degeneration of neurotubules on axons in cross sections of the optic nerve. The axonal counts in eyes subjected to 45 min of ischemia were 29% lower than in control eyes. After 60 min of ischemia, there were distinct disruptions of mitochondria and degeneration of the axons. After 90 min of ischemia, numerous axons showed degeneration with disordered myelin sheaths. Neuronal cell death was seen in the retina, mainly in the ganglion cell layer. • Conclusion: Damage to the retinal ganglion cell layer and the optic nerve was evident after only 45 min of ischemia in normal eyes. This experiment suggests that seriously injured eyes must be protected from high IOP; if IOP elevation is required during vitrectomy, it is essential to reduce the duration of interruption of blood flow to a minimum.     

Time-dependent effects of elevated intraocular pressure on optic nerve head axonal transport and cytoskeleton proteins

PURPOSE: To study the time-dependent effects of elevated intraocular pressure (IOP) on axonal transport and cytoskeleton proteins in the porcine optic nerve head. METHODS: Fifteen pigs were used for this study. Rhodamine-beta-isothiocyanate was injected into the vitreous of each eye to study axonal transport. IOP in the left eye was elevated to 40 to 45 mm Hg, and IOP in the right eye was maintained between 10 and 15 mm Hg. Cerebrospinal fluid pressure was also continually monitored. IOP was elevated for 3 hours (n = 7) or 12 hours (n = 8) before animal euthanatization. Antibodies to phosphorylated neurofilament heavy (NFHp), phosphorylation-independent neurofilament heavy (NFH), neurofilament light, neurofilament medium (NFM), microtubule, and microtubule-associated protein (MAP) were used to study the axonal cytoskeleton. Confocal microscopy was used to compare axonal transport and cytoskeleton change between control and high IOP eyes in different laminar regions and quadrants of the optic nerve head. Results from these experiments were also compared with 6-hour elevated IOP data from an earlier study. RESULTS: Three hours of IOP elevation caused a decrease in NFH, NFHp, and NFM within laminar regions, with no demonstrable change in axonal transport. Changes to MAP and microtubules were only seen after 12 hours of IOP elevation. Axonal transport change occurred in a time-dependent manner with peripheral nerve bundle changes occurring earlier and being greater than central nerve bundle changes. CONCLUSIONS: Time-dependent changes in axonal transport and cytoskeletal structure in the optic nerve head provide further pathogenic evidence of axonal damage caused by elevated IOP.     

Quantitative correlation of optic nerve pathology with ocular pressure and corneal thickness in the DBA/2 mouse model of glaucoma

PURPOSE: To investigate quantitatively the relationships between elevated intraocular pressure (IOP), axonal loss, and corneal thickness in the DBA/2 mouse model of glaucoma, to understand better how these factors contribute to disease progression. METHODS: IOP was measured with a handheld tonometer (Tono-Pen; Medtronic Solan, Jacksonville, FL) in 195 to 446 eyes of mice 2 to 10 months of age sampled from a colony of 400 DBA/2 mice. From a group of 24 eyes at 4, 9, and 10 months of age, correlations were determined between the density and number of RGC axons, corneal thickness, and IOP. RESULTS: Mean IOP levels in the colony were 15 to 16 mm Hg at 2 months of age and rose almost linearly at a rate of 0.9 mm Hg/mo before reaching 22 to 23 mm Hg at 10 months. Both the density and number of axons decreased with increasing average lifetime IOP. IOP variation within age groups strongly correlated with density. Age-matched mice with lower mean IOP had greater preservation of axons in the optic nerve. Elevated IOP was accompanied by increased corneal thickness at the limbus. Surprisingly, corneal thickness was a strong predictor of axonal density (r2 = -0.75), regardless of age. CONCLUSIONS: IOP increased with age in most, but not all, DBA/2 mice. In age-matched mice, differences in IOP corresponded to differences in axonal density and number. In young mice with elevated IOP, the loss of axons resembled that of older animals with similar IOP. Whether corneal thickness is a byproduct of elevated IOP remains unknown, but it may be useful as an index of optic nerve degeneration.     

视神经挫伤轴浆运输和超微结构变化的实验研究

目的 研究实验性视神经挫伤轴浆运输与超微结构的变化。方法采用自行设计的弹簧冲击器对家兔视神经进行定量损伤，术后1、3、7、14d应用辣根过氧化物酶(HRP)顺行标记和透射电镜观察视神经轴浆运输以及超微结构的变化。结果 不同时间实验组HRP反应产物较正常对照组明显降低，差异有显著性，HRP反应产物随观察时间延长逐渐增加，但至术后14d仍明显低于正常。电镜观察见损伤后1d大部分轴突颗粒状变性，线粒体肿胀，髓鞘松解，3d时损伤最重，14d部分轴突恢复正常。结论 视神经挫伤后局部轴浆运输发生障碍，同时轴突变性，14d部分轴突功能恢复。     

Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma

PURPOSE: In both animal model system and in human glaucoma, retinal ganglion cells (RGCs) die by apoptosis. To understand how RGC apoptosis is initiated in these systems, the authors studied RGC neurotrophin transport in experimental glaucoma using acute intraocular pressure (IOP) elevations in rats and chronic IOP elevation and unilateral optic nerve transections in monkeys. METHODS: Eyes were studied in masked fashion by light and electron microscopy and by immunohistochemistry with antibodies directed against the tyrosine kinase receptors (TrkA, B, and C) and against brain-derived neurotrophic factor (BDNF), as well as by autoradiography to identify retrograde axonal transport of 125I-BDNF injected into the superior colliculus. RESULTS: With acute glaucoma in the rat, RGC axons became abnormally dilated, accumulating vesicles presumed to be moving in axonal transport at the optic nerve head. Label for TrkB, but not TrkA, was relatively increased at and behind the optic nerve head with IOP elevation. Abnormal, focal labeling for TrkB and BDNF was identified in axons of monkey optic nerve heads with chronic glaucoma. With acute IOP elevation in rats, radiolabeled BDNF arrived at cells in the RGC layer at less than half the level of control eyes. CONCLUSIONS: Interruption of BDNF retrograde transport and accumulation of TrkB at the optic nerve head in acute and chronic glaucoma models suggest a role for neurotrophin deprivation in the pathogenesis of RGC death in glaucoma.     

Increased elastin expression in astrocytes of the lamina cribrosa in response to elevated intraocular pressure

PURPOSE: To determine whether abnormal elastin synthesis in the glaucomatous optic nerve head and lamina cribrosa is due to elevated intraocular pressure (IOP) or secondary to axonal injury, monkeys with elevated IOP and with optic nerve transection were compared. METHODS: Unilateral, chronic elevated IOP was induced in 11 rhesus monkeys by laser scarification of the trabecular meshwork. IOP was monitored weekly and maintained within 25 to 45 mm Hg for 7 to 36 weeks. In 6 monkeys, unilateral, optic nerve transection was performed, and monkeys were killed after 4 weeks. Optic nerve damage was assessed by stereoscopic slit-lamp biomicroscopy and fundus photography and by confocal scanning laser ophthalmoscopy. The eyes were enucleated and processed for immunohistochemistry and in situ hybridization and for electron microscopic immunogold detection of elastin. Axonal loss was evaluated in cross sections of the optic nerve stained with phenylenediamine. RESULTS: Compared with normal contralateral controls, the lamina cribrosa of eyes with elevated IOP exhibited markedly increased elastin and the presence of elastotic aggregates in the extracellular matrix and upregulation of elastin mRNA in the astrocytes. In transected eyes, elastin appeared as fine fibers in the lamina cribrosa, without elastotic aggregates, and without new synthesis or abnormal deposition of elastin. At the transected site, new synthesis of elastin was present in the pia mater but not in astrocytes in the glial scar. CONCLUSIONS: This study demonstrates that abnormal elastin synthesis in experimental glaucomatous optic neuropathy in the monkey is specific to elevated IOP and not secondary to axonal loss. The mechanisms by which elevated IOP induces enhanced elastin synthesis in laminar astrocytes are unknown but differ from those involved in acute axonal injury such as transection, where inflammation and breakdown of the blood-nerve barrier occur.