Foxn4 is required for retinal ganglion cell distal axon patterning

The regulation of retinal ganglion cell (RGC) axon growth and patterning in vivo is thought to be largely dependent on interactions with visual pathway and target cells. Here we address the hypothesis that amacrine cells, RGCs' presynaptic partners, regulate RGC axon growth or targeting. We asked whether amacrine cells play a role in RGC axon growth in vivo using Foxn4(-/-) mice, which have fewer amacrine cells, but a normal complement of RGCs. We found that Foxn4(-/-) mice have a similar reduction in most subtypes of amacrine cells examined. Remarkably, spontaneous retinal waves were not affected by the reduction of amacrine cells in the Foxn4(-/-) mice. There was, however, a developmental delay in the distribution of RGC projections to the superior colliculus. Furthermore, RGC axons failed to penetrate into the retinorecipient layers in the Foxn4(-/-) mice. Foxn4 is not expressed by RGCs and was not detectable in the superior colliculus itself. These findings suggest that amacrine cells are critical for proper RGC axon growth in vivo, and support the hypothesis that the amacrine cell-RGC interaction may contribute to the regulation of distal projections and axon patterning.     

光化学法建立兔视网膜分支静脉阻塞模型

目的 建立一个与临床特征和病理机制相似的新的视网膜分支静脉阻塞（branch retinal vein occlusion, BRVO）模型。 方法 5只家兔静脉内注入光化学药物孟加拉红，以波长530 nm氪绿激光照射单眼视网膜静脉分支，1 h后行荧光素眼底血管造影(fundus fluorescein angiography, FFA)检查，并于3 d后摘除5只兔眼球做病理切片。 结果 FFA检查证实5只兔眼均有BRVO，病理切片证实5只兔眼阻塞的血管内均有血栓形成。 结论 光化学法可建立和临床病理机制相似的BRVO模型，此法操作简单，为BRVO的临床研究提供了较好的动物模型。 （中华眼底病杂志，2002，18：23-25）     

视盘倾斜综合征黄斑区脉络膜和视网膜色素上皮层厚度观察

目的 观察视盘倾斜综合征（TDS）患者黄斑区脉络膜和视网膜色素上皮（RPE）层厚度。方法 描述性研究。临床检查确诊的TDS患者22例30只眼（TDS组）纳入研究。其中,男性8例11只眼,女性14例19只眼;平均年龄（9.00±2.78）岁。最佳矫正视力（BCVA） 0.3~1.0;平均等效球镜度数（-3.44±2.22） DS。选取同期等效球镜度数相匹配的志愿者15名30只眼作为对照组。其中,男性8名16只眼,女性7名14只眼;平均年龄（9.33±1.11）岁。BCVA均≥1.0;平均等效球镜度数（-3.18±1.13） DS。两组受检者等效球镜度数比较,差异无统计学意义（t=-1.648,P=0.110）。应用频域光相干断层扫描深度增强成像技术测量受检者黄斑中心凹下,通过黄斑中心凹的水平方向和垂直方向距黄斑中心凹鼻侧、颞侧、上方、下方各500、1000、1500、2000 μm处共17个位点的脉络膜、RPE层厚度。定量分析TDS组黄斑区脉络膜、RPE层厚度。结果 TDS组、对照组黄斑中心凹平均脉络膜厚度分别为（235.53±51.77）、（273.45±60.35） μm。两组黄斑中心凹平均脉络膜厚度比较,差异有统计学意义（t=-2.612,P=0.011）。TDS组黄斑中心凹水平（F=24.180）、垂直（F=23.390）方向各位点之间脉络膜厚度比较,差异有统计学意义（P=0.000）;黄斑中心凹水平方向脉络膜厚度除鼻侧1000 μm外,其余各位点脉络膜厚度均较对照组薄,差异有统计学意义（P＜0.05）。垂直方向黄斑中心凹及下方各位点脉络膜厚度均较对照组变薄,差异有统计学意义（P＜0.05）。TDS组、对照组黄斑中心凹平均RPE层厚度分别为（32.56±5.00）、（36.58±3.60） μm。两组黄斑中心凹平均RPE层厚度比较,差异有统计学意义（t=-3.567,P=0.001）。两组RPE层厚度均表现为中心凹处最厚,TDS组RPE层各位点厚度均较对照组变薄,差异有统计学意义（P＜0.05）。结论 TDS患者脉络膜、RPE层厚度均较正常人变薄。     

人胎视网膜血管结构发育的研究

目的；观察人胎视网膜血管结构发育过程。 方法：收集134例12~38周受精龄胎儿和4例成人视网膜，进行整装铺片和切片的免疫组织化学染色检查。 结果：①梭形细胞仅存于小于27周胎儿的视网膜内；足月胎儿节细胞层血管仍有出芽．②各阶段胎儿及成人视网膜血管基膜的纤维连接蛋白免疫反应均呈阳性。层粘连蛋白和Ⅳ型胶原免疫反应分别于25周和29周出现在节细胞层血管基膜，并分别在29周和32周开始完全包裹视网膜内已形成的4层血管．③内皮细胞束管道化时管道外即出现平滑肌细胞和周细胞．④4层血管向锯齿缘扩展的同时，内皮细胞外即有星形腔质细胞和Müller细胞突起形成血—视网膜屏障胶质膜。 结论：与成人比较，不同阶段胎儿视网膜血管均存在一定的缺陷，到足月时内皮细胞仍处在增殖、迁移状态． （中华眼底病杂志，1997，13：153-156）     

颈内动脉重度狭窄患者视网膜神经纤维层与神经节细胞复合体的改变

目的 探讨颈内动脉狭窄患者视盘周围视网膜神经纤维层（peripapillary r etinal n erve f iber l ayer, pRNFL）、黄斑区神经节细胞复合体（ganglion cell complex,GCC）厚度的改变,RNFL缺损、GCC丢失比 例的情况。 方法 回顾分析2015年7月-2016年7月在首都医科大学附属北京天坛医院诊治的单侧颈内动脉重度 狭窄（≥70%）或闭塞患者的病例资料,并纳入经颈动脉超声检查明确颈内动脉无明显狭窄的健康者 作为对照组,通过光学相干断层扫描（optical coherence tomography,OCT）检测病例组及对照组双眼 pRNFL及GCC厚度、RNFL缺损、GCC丢失比例。比较病例组狭窄同侧眼和对侧眼及对照组右眼的上述 数据的差异。 结果 共入组56例颈内动脉狭窄患者和56例对照组。颈内动脉狭窄同侧眼的p R N F L平均厚 度、黄斑区GCC平均厚度[（99.44±14.60）μm,（92.61±10.63）μm]较对侧眼[（107.01±9.96）μm, （96.48±9.73）μm]均薄（P =0.008,P =0.047）;较正常对照组眼的pRNFL平均厚度、黄斑区GCC平均 厚度（[ 110.47±6.48）μm,（96.86±5.00）μm]均薄（P=0.001,P=0.013）。狭窄同侧眼出现RNFL缺损、 GCC丢失的比例（33.9%,53.6%）较对侧眼（12.5%,26.8%）均显著增高（P =0.007,P =0.004）。 结论 颈内动脉重度狭窄可导致pRNFL和GCC厚度变薄,通过OCT检查可以更早发现颈内动脉狭窄对 眼部血供的影响。     

The effect of eccentricity on the contrast response function of multifocal visual evoked potentials (mfVEPs)

mfVEPs were recorded with a 22° radius, 60 sector pattern reversal dartboard stimulus (VERIS) at six contrast levels (10%, 25%, 35%, 50%, 75%, 95%). Contrast response functions (CRFs) based on response amplitudes were adequately described by a simple hyperbolic function. The effect of reducing contrast on the amplitude was most apparent in the central 1° radius, which had a C₅₀ (contrast at 50% of the maximum response) in excess of 50%, compared to values for C₅₀ in more eccentric regions that were 30% or lower. Mean latency increased 6 (±0.7SE) ms from the highest to the lowest contrast tested, and did not vary significantly with eccentricity.     

Electrically-evoked Neural Activities of rd1 Mice Retinal Ganglion Cells by Repetitive Pulse Stimulation

For successful visual perception by visual prosthesis using electrical stimulation, it is essential to develop an effective stimulation strategy based on understanding of retinal ganglion cell (RGC) responses to electrical stimulation. We studied RGC responses to repetitive electrical stimulation pulses to develop a stimulation strategy using stimulation pulse frequency modulation. Retinal patches of photoreceptor-degenerated retinas from rd1 mice were attached to a planar multi-electrode array (MEA) and RGC spike trains responding to electrical stimulation pulse trains with various pulse frequencies were observed. RGC responses were strongly dependent on inter-pulse interval when it was varied from 500 to 10 ms. Although the evoked spikes were suppressed with increasing pulse rate, the number of evoked spikes were >60% of the maximal responses when the inter-pulse intervals exceeded 100 ms. Based on this, we investigated the modulation of evoked RGC firing rates while increasing the pulse frequency from 1 to 10 pulses per second (or Hz) to deduce the optimal pulse frequency range for modulation of RGC response strength. RGC response strength monotonically and linearly increased within the stimulation frequency of 1~9 Hz. The results suggest that the evoked neural activities of RGCs in degenerated retina can be reliably controlled by pulse frequency modulation, and may be used as a stimulation strategy for visual neural prosthesis.     

Adaptive changes of inner retina function in response to sustained pattern stimulation

We have characterized adaptive changes of inner retina function in response to sustained pattern stimulation in 32 normal subjects with an age range 23-77 years by measuring changes of the pattern electroretinogram (PERG) as a function of time. Contrast-reversal stimuli had square-wave profile in space and time, with peak spatial and temporal frequency and high contrast to maximize response amplitude. The PERG signal was sampled over 5 min with a resolution of 15 s. PERG signals were non-stationary, resulting in either progressive amplitude decline or even enhancement to a plateau, with a time course that could be well described by an exponential function with a time constant of 1-2 min. Higher initial amplitudes were generally associated with amplitude decline, and lower initial amplitudes with enhancement. The delta amplitude (plateau minus initial) was a linear function of the initial amplitude. The magnitude of delta decreased with decreasing initial amplitude and inverted its sign for initial amplitudes about 1/3 lower than the maximum initial amplitude measured, but still about 3-4 times larger than the noise. Amplitude decline was generally associated with phase lag, whereas amplitude enhancement was associated with phase advance. Altogether, PERG generators appear to slowly adjust their gain in order to keep their sustained activity at an intermediate level that is rather independent of the level of activity at stimulus onset. This behavior is reminiscent of a buffering mechanism, where glial cells may play a primary role. An energy-budget model of neural-vascular-glial interaction is provided together with an equivalent electrical circuit that accounts for the results.