α糜蛋白酶和地塞米松对兔眼视网膜功能的影响

增殖性玻璃体视网膜病变(Proliferative Vitreo-retinopathy PVR)是眼外伤,视网膜脱离等眼疾的并发症,也是导致视网膜脱离复位术失败的最常见的原因.玻璃体切除术虽能切除眼内的增殖膜,但不能阻止甚至可刺激眼内细胞的增殖,迁移过程,术后PVR常复发.我院近年来应用α糜蛋白酶和地塞米松球侧注射治疗PVR,临床观察有一定疗效,本文将α糜蛋白酶,地塞米松联合应用于兔眼,以观察其对兔眼视网膜电图(ERG),视网膜电图振苗电位(OPS)及视网膜超微结构的影响。材料与方法实验对象为家兔7只,体重1.5—3Kg,右眼为实验     

山莨菪碱滴眼液对兔眼睫状肌及视网膜血流的影响

目的:研究山莨菪碱滴眼液对家兔眼睫状肌松弛和视网膜血流变化的作用,以探讨其防治近视的机制。方法:建立家兔离体睫状肌收缩模型,观察山莨菪碱滴眼液对乙酰胆碱诱导的收缩睫状肌的松弛作用;采用多普勒观察山莨菪碱滴眼液滴眼对家兔视网膜血流的影响。结果:山莨菪碱滴眼液对乙酰胆碱诱导的睫状肌收缩具有松弛作用;能够增加视网膜中央动脉收缩期和舒张期的血流,降低血管阻力指数。结论:山莨菪碱滴眼液通过松弛睫状肌,改善视网膜血循环发挥防治近视的作用。     

糖尿病视网膜病变患者脉络膜厚度和血流动力学参数的变化及其影响因素

目的：：研究糖尿病视网膜病变患者脉络膜厚度和血流动力学参数的变化及其影响因素。方法：选取2013-01/2015-01在我院诊断为2型糖尿病的患者100例100眼,将患者分为3组：无糖尿病视网膜病变( non-diabetic retinopathy,NDR)组患者34例,非增殖期糖尿病视网膜病变( non-proliferative diabetic retinopathy, NPDR)组36例,增殖期糖尿病视网膜病变( proliferative diabetic retinopathy,PDR)组30例。再根据OCT的视网膜黄斑区扫描结果,将糖尿病视网膜病变患者分成两组：糖尿病黄斑水肿( diabetic macular edema,DME)组28例,无糖尿病黄斑水肿组38例。选择同期在我院接受体检的35例正常人群作为对照组。比较各组患者距黄斑中心凹不同距离的脉络膜厚度和鼻侧睫状后动脉的血流动力学参数及其影响因素。结果：随着患者糖尿病视网膜病变的加重,距黄斑中心凹不同距离的脉络膜厚度均呈下降趋势,NPDR和PDR组患者距黄斑中心凹不同距离的脉络膜厚度薄于对照组,差异有统计学意义(P<0.05),NDR组患者距黄斑中心凹不同距离的脉络膜厚度与对照组比较,差异无统计学意义(P>0.05)。糖尿病视网膜病变合并DME患者和非DME患者距黄斑中心凹不同距离的脉络膜厚度比较,差异无统计学意义( P>0.05)。 Pearson相关性分析显示,糖尿病视网膜病变患者脉络膜厚度与糖尿病病程、空腹血糖、HbA1 c、眼轴长度、收缩压及舒张压均无显著相关性(P>0.05),而与logMAR BCVA之间有相关性( P<0.01)。 NDR组和NPDR组患者的PSV和EDV明显低于对照组, RI高于对照组, PDR组患者的PSV和EDV明显低于其他三组,RI高于其他三组,差异有统计学意义(P<0.05)。结论：随着2型糖尿病患者视网膜病变程度的加重,脉络膜厚度呈下降的趋势,脉络膜厚度监测有利于全面分析2型糖尿病视网膜病变患者的病情。     

玻璃体积血对兔眼视网膜影响的研究

目的　观察兔眼玻璃体积血后不同时间视网膜电图（electroretinogram,ERG）及超微结构的变化,为玻璃体积血治疗及预后评估提供实验依据。方法　新西兰大白兔32只,右眼均为实验眼,自体全血0.2 mL玻璃体内注射构建玻璃体积血模型,左眼为空白对照眼。随机分为4组,分别于造模后3 d、7 d、14 d及30 d选取一组常规检查后记录ERG的变化,随后处死动物立即摘取眼球制备标本观察超微结构。结果　实验性玻璃体积血3 d后常规ERG波形消失,造模后7 d逐渐出现。强闪光源刺激下,造模后3 d实验眼ERG的b波振幅与a波振幅与对照眼相比均明显降低（均为P＜0.01）。a波振幅在造模后30 d明显恢复,与对照眼无明显差异（P＞0.05）,较造模后14 d差异有统计学意义（P＜0.05）;b波振幅在造模后7 d时开始回升,与对照眼无明显差异（P＞0.05）,较造模后3 d差异有统计学意义（P＜0.05）,造模后14 d及30 d接近正常。扫描电镜显示实验眼造模后3 d无玻璃体后脱离（posterior vitreous detachment,PVD）发生,造模后7 d部分性PVD占1/8,完全性PVD占1/8,造模后14 d部分性PVD占2/8,完全性PVD占5/8,造模后30 d部分性PVD占1/8,完全性PVD占7/8;对照眼各阶段未见PVD发生。结论　玻璃体积血后约1周可轻度可逆地影响视网膜功能并加速导致PVD形成,为实验及临床判断玻璃体积血后视网膜功能变化和临床玻璃体手术治疗的时间窗的选择提供了参考。     

经瞳孔温热疗法对正常兔眼视网膜脉络膜的影响

目的 探讨影响经瞳孔温热疗法(TTT)治疗效果的因素。方法 健康成年日本大耳白兔8只、青紫兰兔12只分为3组,麻醉、散瞳并安放全视网膜镜,行TTT。结果 光斑直径为1．2mm,暴露时间为1分钟时,正常白兔进行阈值TTT所需的激光功率为1200mW,正常灰兔进行阈值TTT所需的激光功率为110mW;随激光功率的增加视网膜出现颜色改变的同时,光镜下亦出现相应的改变;照射时给眼球一定的压力,使脉络膜循环发生障碍,会加重激光对视网膜的损坏。结论 TTT是一种阈值治疗,阈值上治疗可引起兔眼视网膜组织的不可逆损伤。眼底色素含量与脉络膜循环状态是影响阈值功率选择的重要因素。     

Z,E-butlidedephthalide对大鼠脉络膜新生血管和兔眼血流的影响

目的:研究Z,E-butylidedephthalide(Bdph)对激光诱导的大鼠脉络膜新生血管(CNV)和兔眼脉络膜血流的影响.方法:雄性Brown Norway大鼠行Nd:YAG激光诱导眼底Bruch膜破裂,而后分别予30 mg/kg和15 mg/kg Bdph 1 次/d腹腔注射,连续4 wk.2 wk及4 wk末行眼底荧光血管造影检查.4 wk末制作脉络膜平片测量新生血管的面积.用1 g/L Z,E-butylidenephthalide给雌性新西兰大白兔点眼,采用彩色微球技术测量大白兔眼部血流的变化.结果:和对照组相比,Bdph 30 mg/kg和15 mg/kg组大鼠眼底血管荧光渗漏明显减少,P＜0.01;在此两组中,眼底荧光血管造影测定的新生血管面积以及脉络膜平片测定的新生血管面积都比对照组减少.10 g/L Z,E-butylideneph-thalide滴入兔眼30和60 min后脉络膜血流均比对照组增加,P＜0.05.结论:Z,E-butylidedephthalide可以抑制大鼠脉络膜新生血管的生长,增强兔眼脉络膜血流,可能成为治疗年龄相关性黄斑变性的新药.     

玻璃体切除术对兔眼视网膜电图和超微结构的影响

对19只兔眼行玻璃体切除术，动态观察了术后28天内ERGb波的变化和28天时视网膜结构的变化。结果玻璃体切除后1、4天ERGb波明显降低（P＜0．01），第7天较1.4天回升（P＜0．05），14～28天与术前无显著差异（P＞0．05）。28天时光镜及电镜检查视网膜无明显结构损害。此结果为判断玻璃体手术后疗效、评价玻璃体手术后应用药物对视网膜的毒性作用提供了实验依据。     

负压吸引对兔眼视网膜和视神经的影响

探讨准分子激光原位角膜磨镶术(1aser in situ keratomileusis,LASIK)中眼压急剧升高对视网膜和视神经的影响。方法将LASIK术中使用的巩膜负压环置于兔眼,瞬时压力达到65mm Hg(1mm Hg=0.133kPa),分别持续30s、1min及3min,在光镜和电镜下观察负压吸引后即刻摘除的(即刻组)和2周后摘除的(修复组)兔眼视神经和视网膜组织,并与正常兔眼(对照组)进行比较。结果负压吸引30s,视神经和视网膜细胞改变轻微;负压吸引1min,部分视神经纤维改变,视网膜视细胞出现异常;负压吸引3min,神经纤维和视网膜视细胞结构明显异常。即刻组和修复组组织改变基本相同。结论LASIK术中眼压急剧升高,可导致视网膜和视神经细胞的亚细胞结构改变,且持续时间越长改变越明显。     

去炎松对玻璃体切除兔眼视网膜电图和超微结构的影响

3组12只兔双眼行玻璃体切除术，分别于一眼玻璃体内注入0.5、1.0，2.0mg去炎松悬液，另一眼注入眼用平衡盐液．观察术后28天内眼底及ERGb波和28天时视网膜结构的变化．注入各剂量的去炎松在28天时均未完全吸收，0.5、1 .0mg组用药眼ERGb波在各时间点与对照眼及术前无显著差异(P>0.05)；2.0mg组用药眼较术前无显著差异(P>0.05)，较对照眼有轻度升高(t=3.3589，P>0.05)．光镜及电镜下视网膜结构无损害．表明玻璃体切除后使用有效剂量的去炎松对视网膜仍是安全的． （中华眼底病杂志，1996，12：105-107）     

mGluR5对大鼠视网膜对光反应的调控

目的探索代谢型谷氨酸受体5（mGluR5）对大鼠暗适应视网膜电图（ERG）不同成分的贡献。方法实验研究。出生后30日龄大鼠（RCS-rdy+-p+）12只,暗适应大于12 h后,分别行视网膜下腔注射mGluR5激动剂CHPG[（R,S）-2-chloro-5-hydroxyphenylglycine] 200 µmol（6只,CHPG组）和抑制剂MPEP[2-methyl-6-（phenylethynyl）-pyridine] 200 µmol（6只,MPEP组）,对侧眼注射同等体积PBS作为对照。注射后2 d采用RETI-scan系统记录其系列刺激光强度下（-4.5、-2.5、-0.5、-0.02、0.5 1 logcd×m×s-2）的暗适应ERG。导出数据,采用配对t检验进行双眼间数据比较。结果CHPG组,a、b波幅值在不同光强下均显著降低（除最低光强）（-4.5＜t＜-2.3,P＜0.05）,进一步分析得出a、b波最大幅值（Rmax和Vmax）均明显降低（-4.5＜t＜-2.3,P＜0.05）,但其敏感度均未出现明显变化,且b/a未见明显变化。MPEP组,a、b波幅值在不同光强下均显著升高（除最低光强）（-3＜t＜-2,P＜0.05）,进一步分析得出a、b波Rmax和Vmax均明显升高（-3＜t＜-2,P＜0.05）,但其敏感度均未出现明显变化,且b/a未见明显变化。2组的振荡电位（OPs）与相应的对照眼比较未见明显差别。结论mGluR5激动后,ERG a、b波幅值明显降低,mGluR5主要调控外层视网膜的对光反应。     

Effects of ZX-5 and its optical isomers on ocular blood flow in rabbits and retinal function recovery in rats

AIM: The effects of ZX-5, as nitric oxide (NO) donor, on ocular blood flow has been investigated using colored microsphere technique in previous study. The relationship between the production of NO by ZX-5 and ocular blood flow has been evaluated. ZX-5 has been shown to have strong positive effect on increasing choroidal blood flow. However, the effect of ZX-5 on retinal function recovery, the effects of its optical isomers, (R, R)-ZX-5 and (S, S)-ZX-5, on choroidal blood flow and retinal function recovery have not been studied and merit investigation. · METHODS: Colored microsphere technique was used for in vivo experiments to determine choroidal blood flow of ocular hypertension (40mmHg) in rabbit eyes. Electroretinography was used to measure the b-wave recovery as an indication of retinal function recovery. · RESULTS: (R, R)-ZX-5 increased choroidal blood flow at 10g/L, 50μL instillation into eyes at all time points (P <0.05). (S, S)-ZX-5 was not effective in increasing choroidal blood flow. ZX-5 and (R, R)-ZX-5 showed significant effects in retinal function recovery after ischemia of the retina at all time points (P <0.05); whereas (S, S)-ZX-5 did not show significant effect on recovery of b-wave after ischemia at most time points except at 120 and 240 minutes. · CONCLUSION: ZX-5 and (R, R)-ZX-5 have high potency in increasing the choroidal blood flow and improving the retinal function recovery. It is hoped that they could be used for the prevention/treatment of ocular blood flow related eye diseases.     

Microspheres method for ocular blood flow measurement in rats: size and dose optimization

This study modified the microspheres method by optimizing the dose and size of microspheres (MS) to enable accurate ocular blood flow measurement in rats. Fluorescent MS, either 6, 8, 10 or 15 microm diameter, were administered into the left ventricle of anesthetized adult Brown Norway rat in a dose of either 10(6), 5x10(6), or 10(7). The total number of MS entrapped in retina, choroid and optic nerve (Ntissue) was quantified and compared between size and dose groups. The MS distribution in the retina and their reentry into systemic circulation were evaluated for different sized MS. The results showed that at the 5x10(6) dose, the Ntissue of 8 microm MS was significantly more than either 6 or 10 microm MS in the retina (P<0.02) and optic nerve (P<0.03). The 10 microm MS produced the highest Ntissue for the choroid, as compared with either 8 or 6 microm MS (P<0.03). At the 10(6) dose, no difference of N(tissue) was found between 8, 10, and 15 microm MS in the retina. The 10 microm MS yielded the highest Ntissue in the choroid as compared to 8 and 15 microm MS (P<0.003). The Ntissue for 8 microm MS was higher than both 10 and 15 microm (P<0.01) MS in the optic nerve. No MS (>or=8 microm) reentered the systemic circulation. The 15 microm MS tended to lodge in pre-capillary arterioles and caused significant blood pressure increase during the injection. The blood flow measured with the optimal size MS (mean+/-SE) were 19+/-3.4 and 170+/-35 microl/min in the retina and choroid, respectively; and 0.18+/-0.03 microl/min per mm optic nerve. It is concluded that the 8 microm MS are the optimal size for both retinal and optic nerve blood flow estimation; the 10 microm for the choroid. The optimal dose for the retina was approximately 2.5x10(6), 0.5x10(6) for the choroid, and 5x10(6) approximately 10(7) for the optic nerve. The 15 microm MS are inappropriate for ocular blood flow measurements in rats.     

Effects of N-nitropyrazoles on ocular blood flow of rabbits and retinal function recovery of rat eyes after ischemic insults.

Twelve compounds of N-nitropyrazoles were studied for their effects on ocular blood flow in rabbits and retinal function recovery in rat eyes after ischemic insults. Of the twelve N-nitropyrazoles examined, nine increased choroidal blood flow while five increased retinal blood flow significantly. On the other hand, all twelve compounds increased blood flow in iris and ciliary muscle without exception. As for retinal function recovery after ischemic insult in rat eyes, eight out of the twelve compounds showed more significant facilitation than the control. The structure activity relationship of the N-nitropyrazoles to increase ocular blood flow and to facilitate retinal function recovery after ischemic insults were discussed.     

Effects of dihydrogenation of flavones and number of hydroxy groups in the molecules on ocular blood flow in rabbits and retinal function recovery in rats.

PURPOSE: It has been found that the number of hydroxy groups in the molecule of flavones and flavanones affect the ocular blood flow significantly. However, the effects of dihydrogenation of flavones into flavanones on ocular blood flow and retinal function recovery have not been studied and required investigation. METHODS: The colored microsphere technique and electroretinography method were used for the study of ocular blood flow and retinal function, respectively. RESULTS: Maximum effects on ocular blood flow were obtained when there were 3 hydroxy groups in the molecule of flavones and flavanones. Dihydrogenation of flavones to flavanones increased the ocular blood flow further. The same is true for retinal function recovery after ischemic insult. CONCLUSION: These results indicate that hydrogenation is an excellent way to convert natural flavones into more potent compounds of flavanones.     

Effects of some N-nitropyrazole derivatives on ocular blood flow and retinal function recovery after ischemic insult.

Ocular blood flow and retinal function were determined in this study with colored microspheres and b-wave amplitude of electroretinography, respectively. It was found that N-nitropyrazole analogs can facilitate the retinal function recovery efficiently after ischemic insult primarily through increase of choroidal blood flow specifically. Since age-related macular degeneration (AMD) is caused mainly by the choroidal vascular abnormality and/or insufficiency, these N-nitropyrazole analogs are of potential use in the treatment of AMD.     

Effects of crocin analogs on ocular blood flow and retinal function.

Ischemic retinopathy and age-related macular degeneration are the leading ocular diseases that cause blindness. The etiology of these diseases is due in part to the reduction of blood flow in the retina and/or choroid. Crocin analogs isolated from Crocus sativus L. were found to significantly increase the blood flow in the retina and choroid and to facilitate retinal function recovery. Increased blood flow due to vasodilation presumably improves oxygenation and nutrient supply of retinal structures. These results indicated that crocin analogs could be used to treat ischemic retinopathy and/or age-related macular degeneration. It was noted that disaccharide analogs of crocin, such as crocin-1 and crocin-2, were less potent than monosaccharide analogs of crocin, such as crocin-3 and crocin-4, constituting an interesting structure-activity relationship.     

天然类黄酮分子中羟基基团在兔眼缺血损伤后眼球血流量和视网膜功能恢复的作用

目的:我们最近已报告有些天然类黄酮可影响眼球血流量。为阐明黄酮分子中羟基(OH)的作用,选择黄酮含1-4个羟基基团、附有或无糖、有或无甲氧基团,观察对眼球血流量和视网膜功能恢复的作用。方法:采用彩色微珠技术测定兔眼球血流量,视网膜电图监测视网膜功能的恢复。结果:黄酮含4个游离的羟基基团(毛地黄黄酮),似乎有增加眼球血流量和促进视网膜功能恢复的作用。含3个羟基基团(5,7,4'-三羟基黄酮)可迅速增加眼球血流量和恢复视网膜功能。少于2个羟基基团的黄酮(Chrysin),对眼球血流量无增加作用。黄酮附着有芦丁糖,并含2个游离的羟基和甲氧基团(Diosmin),对眼球血流量和视网膜功能均无作用,但是,含儿茶酚的黄酮附着有葡萄糖时(毛地黄黄酮-7-糖苷),会影响眼球血流量。黄酮附着有甲氧基,并含2个游离羟基基团(Acacetin),均影响缺血损伤后眼球血流量和视网膜功能的恢复。结论:黄酮分子中羟基基团数量的增加,可显著提高眼球血流量和促进视网膜功能的恢复,而在黄酮分子B环上有7个羟基基团和儿茶酚基团时,其作用最显著。     

Effects of hydralazine on ocular blood flow and laser-induced choroidal neovascularization

AIM: To investigate the effect of hydralazine on choroidal blood flow in rabbits and laser-induced choroidal neovascularization (CNV) in rats and on tube formation of human umbilical vein endothelial cells (HUVEC). METHODS: Female New Zealand white rabbits were used with raised intraocular pressure (IOP) of the left eye to 40mmHg. Hydralazine (10g/L) eye drops were instilled and ocular blood flow was measured with colored microspheres technique. Male Brown Norway rats were treated with Nd:YAG laser to break Bruch's membrane. Hydralazine (5, 10, 20g/L) eye drops or saline alone was instilled three times a day for 4 weeks after laser treatment. Fluorescein angiography (FA) and choroidal flat mount were used to measure the area of CNV. Tube formation of HUVEC was studied at different concentrations of hydralazine. RESULTS: With raised IOP to 40mmHg on rabbits, 10g/L hydralazine eye drops enhanced the choroidal blood flow significantly at 30 and 60 minutes after drug instillation. After 4 weeks of drug treatment, 5, 10 and 20g/L hydralazine eye drops all reduced the CNV formation dramatically measured by fluorescein angiography and choroidal flat mount. When HUVEC was cultured on matrix gel for 48 hours, the tube formation of HUVEC were prevented.by hydralazine at 3-30mg /L. CONCLUSION: Hydralazine prevents CNV formation in vivo and HUVEC tube formation in vitro, and enhances rabbits' choroidal blood flow after ischemia. It is hoped that hydralazine could be used to treat age-related macular degeneration in the future.     

Use of the retinal vessel analyzer in ocular blood flow research

Acta Ophthalmol. 2010: 88: 717–722

Abstract.

The present article describes a standard instrument for the continuous online determination of retinal vessel diameters, the commercially available retinal vessel analyzer. This report is intended to provide informed guidelines for measuring ocular blood flow with this system. The report describes the principles underlying the method and the instruments currently available, and discusses clinical protocol and the specific parameters measured by the system. Unresolved questions and the possible limitations of the technique are also discussed.