L-NAME对急性高眼压状态下大鼠视网膜的影响

目的通过对大鼠实验前给予左旋-硝基精氨酸甲脂（L-NAME,NO前体左旋精氨酸类似物）后,观察急性高眼压后大鼠视网膜电图（ERG）b波幅的变化,iNOSmRNA的表达情况。探讨L-NAME和iNOS在高眼压视网膜损伤中的作用。方法Wister大鼠48只随机分为6组,前房加压灌注成高眼压模型,6组分别为高眼压30min,90min组,高眼压90min后12h组;注射L-NAME＋高眼压30min,90min组,注射L-NAME＋高眼压90min后12h组。Alnplaldamk15型视电生理仪检测FERG-b波波幅变化。RT-PCR法检测iNOSmRNA的表达。结果注射L-NAME组的ERG-b波波幅与未用药高眼压组相比,前者明显恢复（P〈0.01）。高眼压30min,90min,高眼压90min后12hiNOSmRNA的表达逐渐增强,但L-NAME组iNOSmRNA的表达明显低于对应的高眼压未用药组（P〈0.01）。结论L-NAME做为一氧化氮合酶的抑制剂,通过抑制iNOS合成,有助于缺血后的视网膜功能的恢复,对视网膜起到保护作用。     

热休克反应对大鼠视网膜缺血再灌注损伤的防御作用

目的 观察热休克反应对大鼠视网膜缺血再灌注损伤的防御作用。 方法 将20只Wistar大鼠20只眼随机分为4组，每组5只大鼠。行前房灌注（perfusion）平衡盐溶液制造急性高眼压模型,为高眼压组(P组)；在制造急性高眼压模型前24 h向大鼠腹腔内注射槲皮素(quercetin) (400 mg/kg)，为高眼压＋槲皮素组(P+Q组)；在制造急性高眼压模型前24 h 热休克(heat shock)大鼠，为高眼压＋热休克组(P+H组)；分别在制造急性高眼压模型前48 、24 h，向大鼠腹腔内注射槲皮素、热休克大鼠，为高眼压＋槲皮素+热休克组(P+Q+H组) 。按照国际临床视觉电生理学会的标准化方案，采用国特医疗系统对热休克反应后实验性高眼压大鼠模型和HSP70被槲皮素特异性抑制后实验性高眼压大鼠模型进行暗适应视网膜电图(dark adapted electroretinogram, D-ERG)、振荡电位(oscillatory potentials, OPs)和明适应E RG(light adapted ERG, L-ERG)记录。采用Western blotting方法检测各组大鼠视网膜HSP 70表达情况。 结果 P+H组大鼠视网膜HSP70表达在各组大鼠中最高，P+Q、P+Q+H组大鼠视网膜HSP70表达受到抑制。前房灌注后各组大鼠ERG各波潜伏期延长、幅值减小，P+H组D-ERG的b波、OPs的O₂波的幅值较P组高。灌注0 h后，P+H组各波幅值显著增高(P值均<0.05)；灌注24 h 后，P+H组大鼠视网膜功能恢复较P组好。P+Q、P+Q+H组大鼠灌注后ERG各波及OPs的O₂波潜伏期最长，幅值最低，甚至消失。 结论 热休克反应可以提高大鼠视网膜细胞对缺血再灌注损伤的防御作用。 （中华眼底病杂志，2003，19：117-120）     

急性甲醇中毒后期的视觉电生理表现

报导了11例(22只眼)急性甲醇中毒后期的视觉电生理检查结果。其中发现闪光视网膜电图(FERG)的b波振幅、闪光视诱发电位(FVEP)、图像视网膜电图(PERG),图像视诱发电位(PVEP)的主波振幅和峰时呈显著异常,P<0.001。结果表明急性甲醇中毒后期不仅损伤视网膜外层,而且还波及视网膜内层的神经节细胞和视路。     

高血糖对实验性糖尿病大鼠视网膜电图的影响

目的观察糖尿病大鼠ERG和OPs的变化情况,探讨糖尿病对大鼠FERG和OPs的影响。方法将100只大鼠分为正常组10只和糖尿病组90只。糖尿病组用STZ造模,6个月后将符合条件的大鼠纳入观察组。检测6、9个月时大鼠ERG和OPs的表现。结果糖尿病大鼠视网膜电图a波、b波、OPs振幅有下降趋势,峰潜时延长,与对照组大鼠相比有差异(P<0.01);9个月时糖尿病大鼠a波、b波、OPs振幅降低,峰潜时延迟,与6个月时比较有显著差异(P<0.01或0.05)。结论高血糖可使糖尿病大鼠ERG和OPs振幅下降,峰潜时延长;且随病程的延长其影响逐渐增强。     

视网膜电图震荡电位的研究进展及其在糖尿病视网膜病变中的应用

视网膜电图震荡电位（OPs）是叠加在视网膜电图b波上升段的数个高频率、有节律的小波。用现行国际临床视觉电生理学会视网膜电图记录标准所得到的OPs是来自视杆、视锥细胞的混合反应。近年来,对OPs的分离、纯化和定量技术取得较大进展。研究发现,视杆和视锥细胞引发的OPs有不同的特性。OPs可客观反映内层视网膜的功能,在糖尿病患者视网膜出现明显血管病变前,OPs即可出现振幅下降。随着对OPs具体成分的深入认识和分离技术的不断提高,纯净和无混杂成分的OPs在糖尿病视网膜病变病理损害发生机制的研究以及早期诊断和疗效随访中可能会发挥重要作用     

利用锥体细胞失功能大鼠和先天性静止性夜盲大鼠对视锥与视杆通路振荡电位的分离研究

背景 振荡电位(OPs)是评估视网膜缺血缺氧性疾病视网膜功能变化的重要工具,利用视网膜退行性病变动物模型对视锥、视杆通路起源的OPs特点进行研究非常重要. 目的 在两种自发性视网膜退行性病变模型大鼠中分离视锥、视杆通路,对比分析视杆、视锥通路起源的OPs波的特点. 方法 采用雄性SD大鼠、锥体细胞失功能(RCD)大鼠、先天性静止性夜盲(CSNB)大鼠各6只,以RETI-scan视觉生理记录系统分别在暗适应(12h)和明适应(10 min)条件下,用不同强度的刺激光(-35、-25、-15、-5、0、5 db)进行刺激,记录各组大鼠的闪光视网膜电图(FERG),通过Matlab 7.0的Butterworth滤波提取OPs,采用快速傅里叶变换(FFT)对所得OPs进行频谱分析.结果 暗适应条件下SD大鼠和RCD大鼠的ERG均可见a波和b波,但CSNB大鼠b波阙如;明适应条件下,SD大鼠和CSNB大鼠可见b波,但RCD大鼠各波阙如.暗适应较高刺激光强度下,SD大鼠和RCD大鼠均有低频(主频)和高频(次频)两个明显的频峰,分别为75 ～ 110 Hz、90～120 Hz和90～ 120 Hz、110 ～ 135 Hz;不同刺激光强度下,CSNB大鼠只有一个频峰,为70～100 Hz.而明适应不同刺激光强度下,SD大鼠和CSNB大鼠均只有一个频峰,分别为75～95 Hz和70～85 Hz.明适应条件下与SD大鼠比较,CSNB大鼠b波隐含时延长,b波振幅明显下降,差异均有统计学意义(P＜0.05);暗适应条件下,RCD大鼠b波隐含时和振幅与SD大鼠比较,差异无统计学意义(P＞0.05);与SD大鼠比较,RCD和CSNB大鼠OPs波振幅下降,隐含时延长,差异均有统计学意义(P＜0.05);明适应条件下不同刺激光强度下CSNB大鼠OPs波的隐含时明显长于SD大鼠,振幅明显低于SD大鼠,差异均有统计学意义(P＜0.05). 结论 视锥、视杆通路起源的OPs有不同特性,自发性视网膜退行性改变大鼠的视杆OPs有两个频峰,正常情况下,视杆通路对OPs的贡献比视锥通路大.     

兔急性高眼压视网膜四种氨基酸含量的动态变化

目的
测定家兔实验性急性高眼压模型视网膜谷氨酸（glutamate，GLU）、天门冬氨酸（aspartate，ASP）、γ-氨基丁酸（γ-aminobutyric acid，GABA）和甘氨酸（glycine，GLY）含量的动态变化。
方法
40只家兔分为8组，每组5只兔，每兔随机选一只眼作为实验眼。1～6组为实验组，实验眼在120 mm Hg（1 mm Hg=0.133 kPa）高压前房灌注持续15、30、45 min和高压灌注持续45 min后恢复正常眼压15、30、45 min时摘除眼球。实验对照组仅作前房穿刺后即摘除眼球。空白对照组直接处死动物摘除眼球。利用邻苯二甲醛柱前衍生法，高效液相色谱仪测定各组兔眼视网膜氨基酸的含量。
结果
高眼压灌注持续15 min组，视网膜GLU水平较实验对照组显著升高（t=5.9814，P=0.0003）；恢复正常眼压15min组，GLU含量再次显著升高，与实验对照眼比较差异显著（t=2.5970，P=0.0318）。ASP、GABA和GLY在实验过程中未发现有统计意义的变化。前房穿刺实验对照组与空白对照组的GLU含量比较无差别。
结论
急性高眼压早期以及恢复正常眼压早期均可导致视网膜GLU含量显著升高。
(中华眼底病杂志, 2002, 18: 146-148)     

早期糖尿病视网膜病变的视网膜电图研究

目的：研究早期糖尿病视网膜病变（diabeticretinopathy,DR) 的视网膜电图震荡电位（Oscillatory potentials,OPs)和图形视网膜电图（Pettern electroretinogram,P-ERG)的变化特点,借以早期诊断DR。方法：对20例（40眼）正常和50例（113眼）糖尿病病人进行OPs和P－ERG检测。结果：当糖尿病病人眼底尚未出现改变时,P－ERG的b波波幅和OPs各子波波幅及总波幅已降低。随着DR的发展,各参数的异常率逐渐上升,各波波幅也随之下降,潜伏期延长。OPs的O3波波幅和总波幅以及P－ERG的b波波幅较其它指标具有较高的敏感性,其中O3波波幅为最敏感的指标。结论：OPs的O3波波幅和总波幅等参数能够作为视觉电生理的功能性指标预测DR的发生,在DR的早期诊断和评价DM的疗效方面有临床应用价值。     

银杏叶提取物EGb761对兔视网膜缺血损伤的保护作用

目的：研究自由基清除剂EGb761对实验性视网膜缺血前后的图形视网膜电图（P-ERG）和形态学的影响,探讨EGb761抗氧化作用及视网膜缺血损伤的发病机制。 方法：升高新西兰白兔眼压至130mmHg持续60min来诱导视网膜缺血,实验组动物给予EGb761,对照组动物给予生理盐水。在缺血前、中、后记录P-ERG波幅变化,并在再灌注19h摘除眼球,作光镜、电镜形态学观察。 结果：缺血60min再灌注19h引起b波振幅降低,视网膜神经节细胞、内核层细胞缺失（调亡、坏死）,给予EGb761后可以改善b波的恢复,并可抑制或减少视网膜细胞损害。 结论：自由基清除剂EGb761可改善视网膜缺血损伤的功能恢复。     

振荡电位和图形视网膜电图在亚临床期糖尿病视网膜病变诊断中的应用价值

目的探讨视网膜电图振荡电位(OPs)和图形视网膜电图(P-ERG)在亚临床期糖尿病视网膜病变中的变化特点,并比较振荡电位和图形视网膜电图检测糖尿病患者视网膜功能异常的敏感性。方法选择确诊为Ⅱ型糖尿病,经检眼镜检查、眼底摄片检查,眼底无糖尿病视网膜病变的60例(120只眼)患者,进行振荡电位 (OPs)和图形视网膜电图(P-ERG)检查,观察亚临床期糖尿病视网膜病变的OPs总波幅及各子波波幅、潜伏期和 P-ERG的b波波幅、潜伏期的变化,并与正常组对照。结果在亚临床期糖尿病视网膜病变时,OPs总波幅及各子波波幅和P-ERG的b波波幅均降低,与正常对照组比较,差异均有显著性;但潜伏期在两组间无明显差异。亚临床期糖尿病视网膜病变组OPs总波幅和P-ERG的b波波幅的异常率分别为51．67％和36．67％,两者间差异有显著性。结论 OPs总波幅及各子波波幅和P-ERG的b波波幅在亚临床期糖尿病视网膜病变时即有改变,波幅的改变比潜伏期改变敏感;OPs检测方法较P-ERG敏感,提示OPs能更早、更准确地反映视网膜微循环机能的变化。因此OPs可作为诊断早期糖尿病视网膜病变较敏感的指标。     

Protective effect of dextromethorphan on the ischemic retinal damage in rabbit]

To investigate the effect of dextromethorphan (DEX), N-methyl-D-aspartate (NMDA) receptor antagonist, on the retinal ischemia, 0.4%DEX hydrobromide was intravenously given to rabbits before, during and after retinal ischemia. Retinal function was monitored by electroretinogram (ERG). Retinal ischemia was induced by increasing intraocular pressure to 130 mmHg for 90 or 120 min. Amplitudes of ERG.b-waves recorded after the 90 min ischemia recovered to 72.5 +/- 9.0% in the DEX group and 38.5 +/- 8.5% in the control group which was given normal saline. The maximal recovery rates of b-wave amplitudes after the 120 min ischemia were 44.0 +/- 7.9% in the DEX group and 21.0 +/- 1.3% in the control group. The recovery rates of the b-wave amplitudes in DEX group were significantly higher than in the control group (p less than 0.01). It was found that the effective dose of DEX was 0.1-0.4%.     

Delayed treatment with dextromethorphan can reduce ischemic retinal damage in rabbit]

Previous studies have suggested that prophylactic treatment by dextromethorphan (DEX), N-methyl-D-aspartate (NMDA) receptor antagonist can protect the retina against ischemia. To investigate the effect of DEX on the proceeding ischemic retina, 0.1% DEX hydrobromide was intravenously administered in rabbits immediately (group A), 1 hour (group B) or 2 hours (group C) after the release from ischemia induced by increasing intraocular pressure to 130 mmHg for 90 min. Normal saline was infused immediately after the release from ischemia as control rabbits. Retinal function was monitored by recording electroretinogram (ERG). Twenty four hours after the release of ischemia, the recovery rates of ERG.b-wave amplitudes in groups A, B and C were 61.3 +/- 3.3, 52.2 +/- 9.0 and 43.6 +/- 8.4% of the preischemic amplitude, respectively. The recovery rate of the group A was higher than that of the control (41.9 +/- 10.6%), while no significant differences were seen between groups B or C and the control. The results suggest that DEX can protect the retina if it is administered immediately after the release of ischemia.     

缺血后适应对视网膜缺血-再灌注损伤的保护作用

背景研究证明,缺血后适应（IPC）对多种组织器官的缺血缺氧损伤均有一定的抵抗作用,但其对视网膜缺血缺氧的作用仍受到关注。目的探讨IPC对大鼠视网膜缺血-再灌注损伤（RIRI）后视网膜结构和功能的保护作用。方法将36只健康雄性Wistar大鼠以随机数字表法分为正常对照组、伪手术组、缺血-再灌注组、IPC组。利用前房灌注生理盐水升高眼压至100mmHg（1mmHg=0．133kPa）维持60min的方法制备RIRI大鼠模型,实施IPC处理鼠亚分为再灌注后即刻、1min、10min组（即IPCⅠ组、IPCⅡ组、IPCⅢ组）,分别于实验后1d、7d行大鼠视网膜电图（ERG）检测,然后用过量麻醉法处死大鼠并制备视网膜切片,行苏木精-伊红染色,对各组大鼠视网膜厚度的变化和视网膜形态进行观察。采用SPSS13．0统计学软件的单因素方差分析对各组大鼠ERG各波振幅恢复率和视网膜厚度值的差异进行比较。结果实验后1d,与正常对照组大鼠比较,伪手术组大鼠视网膜结构接近正常,而缺血-再灌注组及IPCⅠ组、IPCⅡ组、IPCⅢ组大鼠视网膜均出现水肿,可见空泡变性,主要在内丛状层（IPL）及内核层（INL）。缺血-再灌注组及IPCⅠ组、IPCⅡ组、IPCⅢ组大鼠视网膜全层、INL、IPL及视网膜外层厚度值均明显高于正常对照组,差异均有统计学意义（均P〈0．05）。再灌注后7d,缺血-再灌注组大鼠视网膜全层厚度值明显低于正常对照组,差异均有统计学意义（均P〈0．05）,尤以INL、IPL显著。IPCⅠ组、IPCⅡ组、IPCⅢ组大鼠视网膜全层、INL、IPL及视网膜外层厚度值均明显高于缺血-再灌注组,差异均有统计学意义（均P〈0．05）。再灌注后7d,缺血-再灌注组、IPC各组大鼠ERG a波、b波和OPs振幅恢复率明显低于伪手术组和正常对照组大鼠,差异均有统计学意义（均P〈0．05）;而IPCⅠ组、IPCⅡ组、IPCⅢ组大鼠ERG a波、b波和OPs振幅恢复率明显高于缺血-再灌注组,差异均有统计学意义（均P〈0,05）。结论IPC对RIRI具有保护作用,在大鼠模型中,这种保护作用在再灌注后即刻至1min时最强。     

The gradient of retinal functional changes during acute intraocular pressure elevation

PURPOSE: To characterize retinal function during a period of acutely elevated intraocular pressure (IOP) across a wide range of IOPs, including those typically observed in animals with experimental glaucoma. METHODS: Unilateral elevation of IOP was achieved manometrically in adult Brown Norway rats (nine experimental groups; n=4-7 in each; 10-100 mmHg and sham control). Full-field ERGs were recorded simultaneously from treated and control eyes, beginning 75 minutes after IOP elevation. Scotopic ERG stimuli were brief white flashes (-6.1 to 2.7 log cd-s/m2). Photopic ERGs were recorded (1.2-2.7 log cd-s/m2) after 15 minutes of light adaptation (150 cd/m2). Relative amplitude (treated/control, %) of ERG components versus IOP was described with a cumulative normal function. RESULTS: Resting IOP was 12.1 +/- 2.8 mmHg and mean femoral artery pressure was 97.6 +/- 10.7 mmHg. ERG components showed a graded effect dependent on IOP. Systematic delays in the timing of the scotopic threshold response (STR) and photopic b-wave were observed between IOPs of 30 and 40 mmHg. Analysis of amplitudes revealed that the negative STR component (nSTR) and the photopic OPs were the most sensitive to acute IOP elevation. These components were first significantly affected at 50 mmHg, whereas all parameters of middle and outer retinal function (scotopic P2 and P3) remained normal. The nSTR and photopic OPs declined by 50% at IOP <61 mmHg. The scotopic P2, OPs, and positive STR (pSTR) had intermediate sensitivity, such that they were reduced by 50% at IOPs between 61 and 66 mmHg. Scotopic P2 amplitude, but not sensitivity, was significantly reduced by 60 mmHg. At 60 and 70 mm Hg, the decline in P2 amplitude was not attributable to changes in photoreceptor response (P3) amplitude or sensitivity. The least sensitive component was the scotopic a-wave (RmP3) showing a 50% reduction at an IOP of 71 mmHg. CONCLUSIONS: During acute IOP elevation, functional changes progress from the proximal to the distal retina. Alterations in ganglion-cell-related ERG potentials occurred at IOPs (30-50 mmHg) commonly observed in rat experimental glaucoma models. Nonspecific functional changes were observed at acute IOP above 50 mmHg, suggesting that IOP should be maintained below this level in experimental glaucoma models if selective ganglion cell injury is to be sought. Repeated IOP spikes above this level may cause permanent, nonspecific damage, perhaps via ischemic mechanisms. Thus, IOP should be monitored frequently in these models.     

Effects of low molecular weight dextran in intraocular irrigating solutions on ERG B-wave

We examined effects of low molecular weight dextran in intraocular irrigating solutions on in vitro ERGs of the rabbit. A significant difference in ERG b-wave amplitude was observed between dextran-free and 3-4% dextran-added solutions. The b-wave amplitudes were well maintained and even enhanced to 120% of the presubstitution level after 90 minutes incubation with 4% dextran-added solution (15 mM/L bicarbonate, 290 M0sm/kg). It is suggested that low molecular weight dextran might be a useful or, at least, non-toxic agent in intraocular irrigating solutions for maintaining the retinal function with respect to ERG b-wave.     

Dextromethorphan attenuates the effects of ischemia on rabbit electroretinographic oscillatory potentials

Dextromethorphan has been shown to protect against ischemic tissue damage. We investigated the effects of dextromethorphan on electroretinographic oscillatory potentials in retinal ischemia. Retinal ischemia was induced in rabbits by increasing intraocular pressure to 120 mm Hg for 30, 60 or 90 minutes. Dextromethorphan was intravenously administered before ischemia and maintained throughout the whole period of experiments. Oscillatory potentials were recorded before and during ischemia as well as 4 hours of recirculation after ischemia. As expected, all oscillatory potentials were decreased after 60 and 90 minutes of ischemia. However, after 30 minutes of ischemia followed by 4 hours of recirculation, amplitudes of P2 were elevated whereas those of P3 and P4 were decreased with normal P1 amplitudes. Dextromethorphan administration diminished the effects of 30 minutes of ischemia on oscillatory potentials and partially attenuated the effects of 60 minutes of ischemia, whereas the effects of 90 minutes of ischemia could not be reversed by dextromethorphan treatment. These results indicate that electroretinographic oscillatory potentials could be useful indicators to evaluate retinal function in the ischemic condition and that dextromethorphan can attenuate the effects of relatively short periods of ischemia on rabbit electroretinographic oscillatory potentials.Abbreviations DM dextromethorphan - NMDA N—methyl—d—aspartate - OP oscillatory potential     

Quantification of ischemic damage in the rat retina: a comparative study using evoked potentials, electroretinography, and histology

PURPOSE: To identify objective criteria to quantify visual function in the rat for developing therapeutic strategies to protect neuronal cells after ischemia. The impact of ocular ischemia on luminance and frequency-modulated contrast vision was compared with the function of outer retinal cells and the number of intact retinal ganglion cells (RGCs). METHOD: Ischemia was induced in Brown-Norway rats by elevating the intraocular pressure to 120 mm Hg for 30, 45, 60, and 90 minutes. Visual function was evaluated by visual evoked potentials (VEPs) in awake, freely moving rats. Retinal function was analyzed with scotopic and photopic electroretinography (ERG). RGCs were quantified in retinal flatmounts after postischemic injection of tracer into the superior colliculus. RESULTS: The response to flicker stimulation in VEP recordings decreased as the ischemic episodes increased. The susceptibility to ischemic damage was more pronounced when potentials were evoked with stimuli at higher frequencies. In ERG recordings, ischemia reduced oscillatory potentials and photopic flicker responses more intensely than scotopic a- and b-waves. In counting the RGCs, the reduced cell density correlated significantly with all electrophysiological parameters. The duration of ischemia with half-maximal inhibitory effect was between 36 and 58 minutes for VEPs and between 36 and 41 minutes for ERG, and it was 51 minutes for RGCs. CONCLUSIONS: The amounts of reduction in VEPs, ERG, and RGCs differed as the duration of ischemia increased. The electrophysiological parameters presented in this study may serve as a useful addition to morphologic evaluations in future neuroprotection studies in vivo.     

Mouse models of retinal ischemic tolerance

PURPOSE: A brief period of noninjurious retinal ischemia, termed preconditioning, has been documented in rats to afford transient protection from retinal ischemic injury, a phenomenon known as ischemic tolerance. The present study was undertaken to develop and systematically characterize mouse models of ischemic tolerance. METHODS: Retinal ischemic injury was caused by elevating intraocular pressure for 30, 45, or 60 minutes in chloral hydrate-anesthetized ND4 Swiss-Webster mice. Random animals were preconditioned 24 hours earlier with either 5 minutes of retinal ischemia or by exposing conscious animals to hypoxia (11% oxygen) for 2 hours. Flash electroretinograms were recorded 1 day and 1 week after ischemia. At 1 or 4 weeks after ischemia, eyes were perfusion fixed for microscopic examination and quantification of layer thickness and cell counts. RESULTS: Retinal ischemia resulted in significant, duration-dependent reductions in inner retinal layer thickness and cell loss in the inner nuclear and ganglion cell layers. A duration-dependent attenuation in a- and b-wave amplitudes was concomitantly noted. The ischemic and hypoxic preconditioning treatments significantly attenuated the ischemia-induced changes in retinal morphology and function, even after 4 weeks of recovery. Tolerance was observed at 24 hours after ischemic preconditioning, but not at 72 hours. CONCLUSIONS: Two models of retinal ischemic tolerance are presented wherein ischemic or hypoxic preconditioning afforded morphologic and functional evidence of protection from retinal ischemic injury in mice. These two murine models should be useful for studies in mutant mice to elucidate endogenous genetic and molecular mechanisms of retinal protection that may then be used to design treatments for ischemic retinopathies.     

Functional characterization of retina and optic nerve after acute ocular ischemia in rats

PURPOSE: To functionally characterize the status of the rat retina and optic nerve after acute elevation of intraocular pressure (IOP) and to determine the dynamics of the pathologic changes in the ischemic retina and optic nerve. METHODS: Retinal ischemia was induced in rats by acutely increasing the IOP (110 mm Hg/60 minutes). Direct and indirect pupil light reflexes (PLRs) were recorded from the noninjured eye, and electroretinograms (flash and flicker ERG) were recorded from the injured and control eyes before and after surgery. Amplitudes and latencies were calculated for each recording session. RESULTS: Preoperative PLR(ratio)s (indirect/direct PLR) were 76.7 +/- 2.6 (mean +/- SEM). Twenty-four hours after surgery the PLR(ratio) was 15.2 +/- 12.8, 10 days after surgery, 11.6 +/- 9.8; 20 days after surgery, 26.5 +/- 8.0; and 28 days after surgery, 33.27 +/- 9.3. However, at day 35, the PLR had significantly recovered (41.1 +/- 7.3) when compared with the 24-hour postoperative ratios (P < 0.01, repeated-measures ANOVA). Forty-two days after surgery, the PLR(ratio) started to decrease once again in the injured eyes (28.7 +/- 5.9). Electroretinographic amplitudes (full-field flash ERG) followed a similar pattern. Cone responses (flicker ERG) were measured 42 days after surgery and revealed defects in injured eyes (control eyes: 46.6 +/- 2.9 microV, injured eyes: 3.4 +/- 1.7 microV). Histologic analysis revealed ischemic damage to all retinal layers, with the primary defects localized to the central retina. CONCLUSIONS: Acute ocular ischemia causes a significant decrease in retinal function, as measured by PLR and ERG, although over time the rat retina and optic nerve show partial regain of function.     

Electroretinographic abnormalities in a rat glaucoma model with chronic elevated intraocular pressure

The purpose of this study was to determine the ability of electroretinographic (ERG) measurements to document progression of the retinopathy in a rat glaucoma model. Thirty four rats with a chronic intraocular pressure (IOP) elevation induced in one eye by cautery of three episcleral/extra-orbital veins were studied in four separate groups. ERGs were recorded sequentially in Group A rats (n = 12) at baseline, and after approximately 20, 40 and 60 days of high IOP, and in three additional groups of rats (n = 6 or 10 per group) after approximately 58, 30 and 175 days of high IOP, respectively. Scotopic ERG parameters recorded simultaneously from both eyes in Group A rats were: a- and b-wave amplitudes, implicit times, oscillatory potential amplitudes (OPs) determined at three different light-flash intensities, and the light-adapted (photopic) ERG b-wave amplitude. In the other groups of rats, only scotopic ERG a-wave, b-wave and OP amplitudes were measured.In Group A rats that were followed sequentially, all the ERG parameters recorded with attenuated stimuli showed significant time-dependent changes in glaucomatous eyes relative to their contralateral normal eyes, with OPs showing the earliest significant difference after only 3 weeks of high IOP. When different groups of unilateral glaucomatous rats were compared beyond 8 weeks of elevated IOP only the OPs showed a continued decrease with time and good discrimination between glaucoma and normal eyes. Over a 25 week period of high IOP the scotopic OPs measured with attenuated light stimuli declined at the rate of approximately 1.5% per week and provided the best ERG measure to monitor progression of retinal pathophysiology in the vein-occlusion rat glaucoma model.