0.2%酒石酸溴莫尼定滴眼液的降眼压作用

目的证实(0.2%酒石酸溴莫尼定Brimonidine Tartrate)阿法根,滴眼液治疗原发开角型青光眼和高眼压症的降眼压效果及安全性.方法选择1 26例原发性开角型青光眼或高眼压症患者,随机分成试验组(阿法根)和对照组(0.5%噻吗心安).两组均每日点药两次(早8点和晚8点),每次一滴.将点第一滴药后2小时的眼压及连续点药后2周、4周的眼压与基线眼压进行比较研究,同时观察血压、心率等全身及局部副作用.结果试验组点药前平均眼压为25.9±3.2mmHg,点一滴药后2小时平均眼压为17.7±3.8mmHg(下降31.7%),连续点药2周平均眼压为16.2±3.0mmHg,(下降37.5%),4周平均眼压为16.2±3.2mmHg(下降37.5%)对照组点药前平均眼压为25.5±2.5mmHg.点一滴药后2小时平均眼压为18.3±3.7mmHg(下降28.2%),连续点药2周平均限压为1 7.2±2.8mmHg(下降32.5%).4周平均眼压为17.5±3.4mmHg(下降31.3%),经统计学处理两组之间降眼压效果无显著性差异.试验组无明显的局部和全身不良反应发生,对照组则对血压和心率有一定的影响.结论阿法根与0.5%噻吗心安每日两次点药相比,降眼压效果相似,但全身和局部副作用少,可以作为青光眼药物治疗中的一种主要选择.     

拉坦前列素和溴莫尼定抑制激光虹膜周边切除术后眼压升高的对比研究

目的：比较拉坦前列素和溴莫尼定抑制激光虹膜周边切除术后眼压升高的效果。方法：对30只眼进行YAG激光虹膜周边切除术，分别应用拉坦前列素和溴莫尼定，观察术前后眼压变化和术后反应。结果：拉坦前列素组和溴莫尼定组第1、3天抑制眼压升高分别为10.62％、5.75％；3.76％、11.93％，第7天疗效相当；两组出现Tyndall征分别为6、7眼次，差异无显著性。结论：拉坦前列素对于早期闭角型青光眼和溴莫尼定一样具有较强抑制激光术后眼压升高作用。     

大鼠视神经夹伤模型中莫尼定的视网膜节细胞保护作用

目的 :研究莫尼定对大鼠视神经夹伤模型视网膜神经节细胞的保护作用。方法 :实验用SD大鼠 2 0只随机分为用药组 8只和对照组 12只。所有大鼠右眼用 40 g微型视神经夹紧贴球后夹持视神经 60秒 ,左眼未做夹持。用药组于夹伤前1小时及夹伤后每日腹腔注射莫尼定 1mg/kg ,阴性对照组于夹伤前 1小时及夹伤后每日腹腔注射生理盐水 5ml/kg ,实验观察2 8天。实验结束前 4天双上丘注射 3 %荧光金逆行标记视网膜神经节细胞。做视网膜铺片 ,距离视乳头中心上下左右各2mm拍摄照片 ,使用CPAS图像分析软件做节细胞定量分析 ,节细胞存活率 =右眼节细胞密度 /左眼节细胞密度× 10 0。结果 :用药组、对照组节细胞存活率分别为 61 0 1%和 53 48% ,两者之间存在显著性差异 (P =0 .0 3 5)。结论 :在大鼠视神经夹伤模型中 ,莫尼定具有明显的视网膜节细胞保护作用     

国产酒石酸溴莫尼定滴眼液的降眼压作用

目的:比较国产酒石酸溴莫尼定滴眼液(brimonidinetar-trateeyedrops)与进口同类药品阿法根滴眼液治疗青光眼和高眼压症的临床疗效及安全性。方法:原发性开角型青光眼或高眼压症患者240例,多中心随机双盲分成试验组(2g/L国产酒石酸溴莫尼定滴眼液)和对照组(阿法根滴眼液)。两组均每日点药2次(08∶00和20∶00),每次1滴。将点第1滴药后2h的眼压及连续点药后1,2,4wk的眼压与基线眼压进行比较研究,同时观察血压、心率等全身及局部副作用。结果:试验组点药前平均眼压为23.74±4.77mmHg,点1滴药后2h平均眼压为19.38±4.51mmHg(下降17.58%),连续点药1wk平均眼压为18.34±4.57mmHg(下降22.19%),2wk平均眼压为18.42±4.32mmHg(下降21.73%),4wk平均眼压为18.56±4.46mmHg(下降21.06%);对照组点药前平均眼压为24.54±5.66mmHg点1滴药后2h平均眼压为20.60±5.70mmHg(下降15.46%),连续点药1wk平均眼压为19.79±6.50mmHg(下降18.82%),2wk平均眼压为19.46±5.05mmHg(下降19.59%),4wk平均眼压为19.73±5.68mmHg(下降18.73%),经统计学处理两组之间降眼压效果无显著性差异。试验组和对照组均无明显的局部和全身不良反应发生。结论:国产2g/L酒石酸溴莫尼定滴眼液与阿法根滴眼液用于治疗原发性开角性青光眼与高眼压症,两者降眼压效果相似,全身和局部副作用小。     

单剂量0.15%酒石酸溴莫尼定对正常个体脉络膜厚度的影响

目的：通过使用频域相干光学断层深度增强成像测量正常个体脉络膜厚度(CT)以评估眼部使用0.15%酒石酸溴莫尼定对眼后节的潜在影响。

方法：前瞻性、安慰剂对照干预性临床试验,包括32例32眼正常个体。第1d,受试者接受一滴无防腐剂人工泪液作为安慰剂; 第2d,接受一滴0.15%酒石酸溴莫尼定。收集每次用药前及用药后1、3和5h,眼压,眼灌注压(OPP)以及EDI-SD-OCT数据。

结果：相较于最初测量结果,局部应用0.15%酒石酸溴莫尼定后,在下凹(P=0.001),颞凹1500μm 处(P=0.003),鼻凹1500μm处(P=0.003)测得脉络膜厚度显著增加。整个研究过程中,安慰剂组脉络膜厚度未发生变化(P>0.05)。分别使用安慰剂和溴莫尼定后眼灌注压没有显著降低(P>0.05)。研究中未观察到不良反应。

结论：与预期相悖,局部应用0.15%酒石酸溴莫尼定导致下凹、颞凹、鼻凹处脉络膜厚度增加。这一结论可能与脉络膜血管自动调节机制有关。     

0．2％酒石酸溴莫尼定滴眼液对国人瞳孔影响的观察

目的本研究旨在探讨0.2%酒石酸溴莫尼定滴眼液(阿法根)在不同亮度条件下对正常人瞳孔大小的影响。方法24名志愿者的右眼给与0.2%阿法根滴眼液1滴,在给药前及给药后30 m in、4 h和6 h分别以红外线瞳孔测量仪在不同亮度条件下测定瞳孔的大小。结果在亮条件下(150 cd/m2)及暗条件下(0.2 cd/m2),相对于给药前的瞳孔平均直径,给药后30 m in、4 h和6 h后的瞳孔平均直径均明显减小,以上数值分别为:(4.7±0.5)mm、(3.6±0.4)mm、(3.7±0.5)mm和(3.8±0.6)mm(P<0.05);(6.1±0.6)mm、(4.3±0.3)mm、(4.0±0.6)mm和(4.7±0.52)mm(P<0.05)。结论0.2%阿法根对正常人瞳孔有着显著的缩瞳作用,符合α2-肾上腺素能受体激动后反馈抑制肾上腺素释放的药理学作用。     

O.2%酒石酸溴莫尼定滴眼液对国人瞳孔影响的观察

目的本研究旨在探讨0.2%酒石酸溴莫尼定滴眼液(阿法根)在不同亮度条件下对正常人瞳孔大小的影响.方法24名志愿者的右眼给与0.2%阿法根滴眼液1滴,在给药前及给药后30 min、4 h和6 h分别以红外线瞳孔测量仪在不同亮度条件下测定瞳孔的大小.结果在亮条件下(150 cd/m2)及暗条件下(0.2 cd/m2),相对于给药前的瞳孔平均直径,给药后30 min、4 h和6 h后的瞳孔平均直径均明显减小,以上数值分别为(4.7±0.5)mm、(3.6±0.4)mm、(3.7±0.5)mm和(3.8±0.6)mm(P＜0.05);(6.1±0.6)mm、(4.3±0.3)mm、(4.0±0.6)mm和(4.7±0.52)mm(P＜0.05).结论0.2%阿法根对正常人瞳孔有着显著的缩瞳作用,符合α2-肾上腺素能受体激动后反馈抑制肾上腺素释放的药理学作用.     

神经营养素家族因子对视网膜神经细胞保护作用的研究进展

现有大量研究表明神经营养素家族因子对视网膜神经细胞具有重要的保护作用。在所有家族成员中,神经生长因子能够有效保护视网膜光感受器细胞;阻断视网膜神经节细胞中神经生长因子与受体p75的结合,可以抑制神经节细胞的凋亡。脑源性神经营养因子可以防止光感受器细胞变性,增强光感受器细胞损伤后的修复。在刺激神经节细胞轴突生长和突触形成方面,脑源性神经营养因子、神经营养素-3及神经营养素-4/5均具有显著效应。通过对神经营养素家族因子的研究,了解其作用机制,以期能够应用于视网膜神经细胞变性及损伤性疾病的治疗中。     

神经生长因子对视网膜脱离视细胞保护作用的实验研究

目的 探讨神经生长因子(NGF)对视网膜脱离(RD)视细胞损伤的保护作用。方法 选用健康青紫蓝兔36只随机分为正常对照组、NGF治疗组和生理盐水(NS)模型组，实验组右眼RD模型制作后，NGF治疗组每天结膜下注射NGF0．1mL(1mg／mL)2次；NS模型组每天结膜下注射NS0．1mL，2次；实验动物于3d、14d后处死，取眼球壁做光镜、电镜检查。结果 光镜、电镜检查NGF治疗组内外节损害较轻、视细胞数较多、外核层较厚、视网膜结构和层次排列较好。NGF治疗组视网膜外核层凋亡细胞计数少于NS模型组。视网膜脱离后14d外核层厚度NGF治疗组厚于NS模型组；NGF治疗组视网膜外核层细胞计数多于NS模型组。结论 结膜下注射NGF对视网膜脱离后视细胞损伤有一定的保护作用。     

正常人眼单独或联合使用溴莫尼定Dorzolamide后房水流动的变化

目的：测量和比较表面使用0．2％溴莫尼定酒石酸盐与2％ Dorzolamide作为人眼房水流动抑制剂的效果，并测量其两协同作用的效果。设计：在20位正常人中进行随机、双盲、安慰剂对照研究。测量日之前表面滴用药物每天两次，测量当日早晨滴一次。在单独给药和联合给药之后，于8AM和4PM通过荧光测定仪测量使用的荧光素清除率以测定房水流速，并用压平式眼压计测量眼压。     

Neuroprotective effects of brimonidine against transient ischemia-induced retinal ganglion cell death: a dose response in vivo study

The purpose of this study was to investigate the dose-response effects of topically administered brimonidine (BMD) on retinal ganglion cell (RGC) survival, short and long periods of time after transient retinal ischemia. In adult Sprague-Dawley rats, RGCs were retrogradely labeled with the fluorescent tracer fluorogold (FG) applied to both superior colliculi. Seven days later, the left ophthalmic vessels were ligated for 90 min. One hr prior to retinal ischemia, two 5 microl drops of saline alone or saline containing 0.0001, 0.001, 0.01 or 0.1% BMD were instilled on the left eye. Rats were processed 7, 14 or 21 days later and densities of surviving RGCs were estimated by counting FG-labeled RGCs in 12 standard regions of each retina. The following have been found. (1) Seven days after 90 min of transient ischemia there is loss of approximately 46% of the RGC population. (2) topical pre-treatment with BMD prevents ischemia-induced RGC death in a dose-dependent manner. Administration of 0.0001% BMD resulted in the loss of approximately 37% of the RGC population and had no significant neuroprotective effects. Administration of higher concentrations of BMD (0.001 or 0.01%) resulted in the survival of 76 or 90%, respectively, of the RGC population, and 0.1% BMD fully prevented RGC death in the first 7 days after ischemia. (3) Between 7 and 21 days after ischemia there was an additional slow cell loss of approximately 25% of the RGC population. Pre-treatment with 0.1% BMD also reduced significantly this slow cell death. These results indicate that the neuroprotective effects of BMD, when administered topically, are dose-dependent and that the 0.1% concentration achieves optimal neuroprotective effects against the early loss of RGCs. Furthermore, this concentration is also effective to diminish the protracted loss of RGCs that occurs with time after transient ischemia.     

阿法根治疗视网膜缺血损伤的实验研究

目的 研究阿法根(alphagan)对动物模型视网膜缺血损伤的神经保护作用。方法 新西兰大耳白兔30只,分为正常对照组、损伤对照组和损伤治疗组,通过急性升高眼压的方法,制成视网膜缺血损伤动物模型,在视网膜缺血前1 h结膜囊内给予0.2％阿法根滴眼液局部治疗。于第7 d观察图形视网膜电图(P-ERG)b波振幅变化,进行组织形态学观察和视网膜神经节细胞(RGC)计数分析。结果 损伤对照组与损伤治疗组相比,相对b波振幅恢复率分别为(6.20±4.60)％和(63.78±9.27)％(t=17.60,P<0.01),RGC的丢失率(43.26±12.42)％和(11.74±6.69)％(t=7.07,P<0.01),明显保护了视网膜的组织形态结构。结论 局部应用阿法根治疗具有一定的神经保护作用。     

Evaluation of neuroprotective qualities of brimonidine during LASIK

PURPOSE: The effects of LASIK-induced increased intraocular pressure on the optic nerve and nerve fiber layer are poorly understood. This study evaluates the effect of LASIK on several optic nerve parameters, both structural (scanning laser polarimetry) and functional (automated perimetry). In addition, the potential neuroprotective effect of perioperative brimonidine is studied. DESIGN: Randomized self-controlled, masked trial. PARTICIPANTS: Fifty-one patients scheduled for routine, bilateral, myopic LASIK. Patients served as their own control and received brimonidine in one eye and placebo in their fellow eye. METHODS: Patients were treated with the VISX Star S3 Excimer Laser. Patients were evaluated preoperatively and at 1 day, 1 month, and 3 months after LASIK. Topical brimonidine or control vehicle was administrated three times daily for 3 days before surgery. In addition, 1 drop of the respective study drug was instilled at the end of the procedure, and the patient continued the study drug three times daily for 3 weeks after surgery in the respective (randomized) eye. MAIN OUTCOME MEASURES: Visual acuity, nerve fiber layer analysis, automated visual field, contrast sensitivity, color vision, and pupillary function. RESULTS: Brimonidine did not change the outcome of any of the parameters analyzed in this study. There was not a statistically significant change in any of the visual field parameters (mean elevation or depression, pattern standard deviation, and corrected pattern standard deviation) measured in either the placebo or brimonidine group postoperatively. However, both the placebo and brimonidine group did show a statistically significant change in many of the direct Nerve Fiber Analyzer GDx (NFA GDx) measures. The average thickness, ellipse, and superior average were generally reduced in both groups. There was, however, no statistically significant change after LASIK in either group in indirect NFA GDx parameters such as symmetry, superior ratio, inferior ratio, or superior/nasal ratio. There was no significant change in optic nerve appearance, contrast sensitivity, or color vision between treatment groups before or after LASIK. CONCLUSIONS: LASIK with or without brimonidine did not affect the structure or function of the parameters of the optic nerve studied. Direct NFA GDx measures were globally reduced after myopic LASIK; however, the ratio measures were generally unaffected. The reduction in direct, retinal nerve fiber layer measures, in the absence of change in ratio measures and other optic nerve parameters and absence of brimonidine effect, suggest an alteration in corneal birefringence after excimer laser ablation.     

米诺环素对视网膜神经保护作用的研究进展

米诺环素（minocycline）是一种第2代人工半合成的四环素类药,口服吸收好,脂溶性高,可穿透血-脑屏障,对人安全,已在中枢神经系统和视网膜疾病中表现出显著的神经保护作用。已知视网膜小胶质细胞在多种视网膜疾病中均有激活并参与病变发展,而米诺环素神经保护作用机制主要为抑制小胶质细胞和caspase-3激活。本文对米诺环素神经保护作用机制及在视网膜疾病中的保护作用做一综述。     

Possible implications of acid-sensing ion channels in ischemia-induced retinal injury in rats

Background

Retinal ischemia in eyes with diabetic retinopathy and retinal vein occlusion leads to local tissue acidosis. Acid-sensing ion channels (ASICs) are expressed in photoreceptors and other neurons in the retina, and may play a role in acid-induced cell injury. The purpose of this study was to investigate the neuroprotective effects of amiloride, an ASIC blocker, on induced retinal ischemia in rats.

Methods

Transient retinal ischemia was induced in male Long–Evans rats by the temporary ligation of the optic nerve. Just before the induction of ischemia, the experimental eyes underwent intravitreal injection of amiloride. On day 7, the retinal damage in eyes that underwent amiloride treatment (and in those that did not undergo the treatment) was evaluated by histology and electroretinogram (ERG).

Results

Transient retinal ischemia caused retinal degeneration with thinning of the inner layer of the retina. The blockage of ASICs with amiloride significantly prevented retinal degeneration. ERG demonstrated that the reduction in a- and b-wave amplitudes induced by the transient retinal ischemia was significantly prevented by the application of amiloride.

Conclusions

The present study suggests that ASICs might, at least in part, play a pathophysiological role in ischemia-induced neurodegeneration. Blockage of ASICs may have a potential neuroprotective effect in ocular ischemic diseases.     

Characterization of brimonidine transport in retinal pigment epithelium

PURPOSE: To investigate the involvement of carrier-mediated transport mechanisms in brimonidine transport in retinal pigment epithelium (RPE). METHODS: The transport of [3H]-brimonidine in bovine RPE-choroid explants was evaluated in a modified Ussing chamber. The uptake of [3H]brimonidine was evaluated in differentiated ARPE-19 cells cultured on permeable transwell filters. RESULTS: The transport of brimonidine into (choroid-to-retina transport [inward]) and out of (retina-to-choroid transport [outward]) the eye in bovine RPE-choroid explants was temperature dependent. Both inward and outward brimonidine transport decreased at 5 microM compared with 10 nM. The melanin pigmentation of RPE did not significantly affect tissue permeability at either brimonidine dose. A saturable component was identified for the inward transport with the apparent Michaelis-Menten constant and a maximum transport rate of 51 microM and 148 pmol/(cm2 x h), respectively. Both apical (representing retina-to-choroid transport) and basolateral (representing choroid-to-retina transport) brimonidine uptake in ARPE-19 cells showed temperature dependence. Apical uptake was higher than basolateral uptake at 37 degrees C and was decreased to 70% in the presence of NaN3 or in the absence of extracellular Na+. Besides alpha2-agonists, apical uptake was inhibited by verapamil, desipramine, and quinidine, but not by MPP+ (1-methyl-4-phenylpyridinium), TEA (tetraethylammonium), decynium-22, carnitine, PHA (p-aminohippurate), alanine, or inosine. Basolateral brimonidine uptake increased by 35% at extracellular pH of 6 and decreased by 50% under cell-depolarized conditions of high medium K+ and 1 microM valinomycin. Temperature-dependent components of basolateral uptake were not saturated at doses up to 2 mM. CONCLUSIONS: A carrier-mediated transport process for brimonidine in RPE was demonstrated in bovine RPE-choroid explants and polarized ARPE-19 cells. This transport system may play a significant role in modulating the movement of brimonidine into and out of the eye.     

骨髓间充质干细胞神经保护作用在视网膜疾病治疗中的研究进展

骨髓间充质干细胞（ MSCs）是来源于骨髓的具有多种神经营养因子分泌功能的多能干细胞,被广泛应用于组织、细胞的修复或替代研究中。有研究表明MSCs分泌的多种神经营养因子,有助于提高病理状态下神经细胞的存活能力。因此,MSCs的神经保护功能也逐渐被应用于视网膜疾病的研究中。视网膜细胞对损伤非常敏感且自我修复能力较差,利用MSCs的这一功能可为病变视网膜的治疗带来新的希望。本文就MSCs的神经营养因子分泌功能及其对视网膜细胞产生的神经保护作用和在不同视网膜疾病中的研究应用进展等方面进行综述,并展望其在视网膜疾病治疗中的应用前景。     

Selective effects of retinal dopamine depletion on partial ischemia-induced electroretinographic hyperresponses in rabbits

The interaction of retinal dopamine depletion and partial ischemia on the a- and b-wave amplitudes and implicit times of the electroretinogram was examined in adult pigmented rabbits. Seven days after 6-hydroxydopamine treatment, which resulted in a depletion of the amine, partial retinal ischemia was induced by raising the intraocular pressure. As expected, moderate elevation of intraocular pressure produced increases in both a- and b-wave amplitudes. Amplitude hyperresponses were significantly reduced in dopamine-depleted retinas. These reductions were more prominent with relatively lower intensities. However, response delays were not shortened but lengthened by 6-hydroxydopamine pretreatment. Together, these results point to a selective role of dopamine in partial retinal ischemia induced by moderate elevation of intraocular pressure in rabbits.