Impaired retinal vasodilator responses in prediabetes and type 2 diabetes

Purpose: In diabetes, endothelial dysfunction and subsequent structural damage to blood vessels can lead to heart attacks, retinopathy and strokes. However, it is unclear whether prediabetic subjects exhibit microvascular dysfunction indicating early stages of arteriosclerosis and vascular risk. The purpose of this study was to examine whether retinal reactivity may be impaired early in the hyperglycaemic continuum and may be associated with markers of inflammation. Methods: Individuals with prediabetes (n = 22), type 2 diabetes (n = 25) and healthy age and body composition matched controls (n = 19) were studied. We used the Dynamic Vessel Analyzer to assess retinal vasoreactivity (percentage change in vessel diameter) during a flickering light stimulation. Fasting highly sensitive c‐reactive protein (hs‐CRP), a marker of inflammation, was measured in blood plasma. Results: Prediabetic and diabetic individuals had attenuated peak vasodilator and relative amplitude changes in retinal vein diameters to the flickering light stimulus compared with healthy controls (peak dilation: prediabetic subjects 3.3 ± 1.8%, diabetic subjects 3.3 ± 2.1% and controls 5.6 ± 2.6%, p = 0.001; relative amplitude: prediabetic subjects 4.3 ± 2.2%, diabetic subjects 5.0 ± 2.6% and control subjects 7.2 ± 3.2%, p = 0.003). Similar findings were observed in retinal arteries. Levels of hs‐CRP were not associated with either retinal vessel response parameters. Conclusion: Retinal reactivity was impaired in prediabetic and type 2 diabetic individuals in parallel with reduced insulin sensitivity but not associated with levels of hs‐CRP. Retinal vasoreactivity measurements may be a sensitive tool to assess early vascular risk.     

Myopia induced by flickering light in guinea pigs:a detailed assessment on susceptibility of different frequencies

AIM:To investigate the effectiveness and feasibility of inducing myopia in guinea pigs by flickering light (FL) stimulation with different frequencies. METHODS: Seventy 2-week-old guinea pigs were randomly assigned to six groups:five FL groups and a control group (n=12 for each). Animals in the five FL groups were raised under 500lx illumination with a duty diurnal cycle of 50% at a flash rate of 5, 1, 0.5, 0.25 and 0.1Hz respectively. Those in the control group were reared under steady 250lx illumination. Refraction, axial length, and radius of curvature were measured before and at 2, 4, 6, 8, 10 and 12 weeks after treatment. At week 12, the eyeballs were taken out and three ocular dimensions and dry weight of sclera were measured. RESULTS: A myopic shift and axial eye length increase developed in the five FL groups. Stimulation at 0.5Hz caused greater changes in myopic shift, axial elongation, eyeball dimension, and dry weight of sclera than stimulation at other frequencies. Compared with controls, eyes in 0.5Hz group were approximately -5.5±1.5D more myopic with increase in horizontal, vertical, axial dimensions by 0.89±0.3mm, 0.69±0.2mm, 1.12±0.2mm respectively and with increase in dry weight of sclera by 0.44mg. CONCLUSION: Chronic exposure to periodic illumination at temporal frequency is attended by development of excessive ocular enlargement and myopic refractive error. Emmetropization could be disrupted differently by frequency alteration.     

Dopamine and nitric oxide control both flickering and steady-light-induced cone contraction and horizontal cell spinule formation in the teleost (carp) retina: serial interaction of dopamine and nitric oxide

Adaptation to ambient light, which is an important characteristic of the vertebrate visual system, involves cellular and subcellular (synaptic) plasticity of the retina. The present study investigated dopamine (DA) and nitric oxide (NO) as possible neurochemical modulators controlling cone photomechanical movements (PMMs) and horizontal cell (HC) spinules in relation to steady and flickering light adaptation in the carp retina. Haloperidol (HAL; a nonspecific DA receptor blocker) or cPTIO (a NO scavenger) largely inhibited the cone PMMs and HC spinule formation induced by either steady or flickering light. These results suggested that both DA and NO could be involved in the light-adaptation changes induced by either pattern of input and that DA and NO effects may not be completely independent. The possibility that NO and DA interact serially was evaluated pharmacologically by cross-antagonist application (i.e., DA + cPTIO or NO + HAL). When a NO donor was coapplied with HAL to dark-adapted eyecups, normal light-adaptive cone PMMs and HC spinules occurred. In contrast, when DA was applied in the presence of cPTIO, the dark-adapted state persisted. It was concluded 1) that DA and NO are both light-adaptive neurochemicals, released in the retina during either steady or flickering light; 2) that the effects of DA and NO on light-adaptive cone PMMs and HC spinules do not occur in parallel; and 3) that NO and DA act mainly in series, specifically as follows: Light --> DA --> NO --> Cone PMMs + HC spinules.     

Tuning the power spectrum of physiological finger tremor frequency with flickering light

Fast Fourier Transform analyses were performed on finger tremor movements at 0.2-Hz intervals from 0.4 to 40 Hz in 10 human subjects, under a flickering light condition of 4-15 Hz and an unstimulated control condition. Under the control condition, the power spectrum showed an essentially normal curve distribution, except for an early frequency component in the histogram. In contrast, when the flickering light stimulus was presented, the power of specific frequency components at 8-11 Hz was strongly enhanced. This effect was induced exclusively at a frequency of 8, 9, or 11 Hz of flickering light, and this flickering frequency producing the enhancement effect differed from subject to subject. There existed a significant correlation between the frequencies of flicker and tremor at the tuned frequency. These findings demonstrate that a specific frequency of flickering light can intensify a specific frequency of physiological finger tremor, and that different individuals exhibit different optimal "tuning" frequencies.     

Switching Between Two Types of Bursting Activity of Single Ca+2-Activated K+ Channels in Dissociated Neurons

Single channel recordings of Ca²⁺-activated K⁺ currents were made from dissociated cockroach neurons by means of the gigaohm-seal patch-clamp technique. Bursts of single channel openings were composed of two distinct classes: the 'long-open burst' contained groups of long, rectangular, pulse-like openings with durations of 3.5 to 1.2 ms (depending on membrane potential), whereas the 'flickering burst' consisted of clusters of brief openings with an average duration of 0.4 ms (voltage-independent) separated by short closings with a duration of about 1.0 ms. The long-open burst and the flickering burst appeared to reflect distinct states of a single Ca²⁺-activated K⁺ channel because direct transitions between these two types of burst were often detected. We present a kinetic scheme for the gating activation pathway of a neuronal Ca²⁺-activated K⁺ channel, based on these findings.     

豚鼠频闪光诱导性近视和形觉剥夺性近视外侧膝状体多巴胺含量的比较

目的 观察豚鼠频闪光诱导性近视和形觉剥夺性近视模型中外侧膝状体多巴胺(DA)含量的变化,并进行对比分析,初步探讨比较不同近视模型的中枢发病机制?方法 24 只普通级2 周龄豚鼠随机分成3 组(n =8):频闪光照(FLM)组?形觉剥夺(FDM)组?对照组,各组均饲养8 周?在造模前后分别测量各组豚鼠右眼屈光度和眼轴长度,8 周实验结束后采用高效液相色谱电化学检测法(HPLC?ECD)对左脑外侧膝状体DA 进行定量?结果 造模前,各组屈光度和眼轴长度差异无显著性( P >0.05)?造模第8 周,与对照组相比,FLM 组和FDM 组右眼屈光度变化值( P <0.001)?眼轴长度变化值( P <0.05)差异均有显著性,提示近视建模成功?HPLC-ECD 结果显示:豚鼠左脑外侧膝状体DA 含量FLM 组> 对照组> FDM 组;对照组为(37.04 ±1.18)pg/ μL; FDM 组为(24.27 ± 3.46)pg/ μL,与对照组相比差异有显著性( P = 0.021);FLM 组为(45.58 ± 1.98)pg/ μL,与对照组相比差异有显著性( P =0.01)?结论 频闪光诱导性近视模型外侧膝状体DA 含量增加,而形觉剥夺性近视模型中DA 含量减少,说明DA 在两种实验性近视外侧膝状体中的表达不一致,两种近视模型的发生机制可能不同?     

基于红细胞膜闪烁多尺度样本熵对贮存红细胞质量评估的研究

目的研究红细胞膜闪烁的多尺度样本熵以提出一种用于分析贮存中红细胞质量变化的途径。方法对于红细胞连续灰度图像序列,通过建立细胞模板的方法提取膜闪烁强度,并且通过多尺度样本熵算法计算经过不同贮存时间的红细胞膜闪烁的多尺度复杂度,并与传统生化方法结果进行对比。结果红细胞膜闪烁的多尺度样本熵会随着红细胞贮存时间的增长而减小,在较短时间（1～5d）的贮存期内会有显著变化。结论红细胞的活性和质量均会随着贮存时间的增长而降低,这与使用传统生化方法分析红细胞质量的结果一致。可望提供一种分析贮存中红细胞质量变化的新途径。     

短波视蛋白在豚鼠频闪光诱导性近视和形觉剥夺近视眼模型中的表达差异

目的 观察豚鼠频闪光诱导性近视和形觉剥夺近视模型中短波视蛋白（S-opsin）表达差异,并初步探讨原因。方法 36只普通级2周龄豚鼠随机分成三组：频闪组（FLM组,n=13）,形觉剥夺组（FDM组,n=12）,对照组（n=11）。FLM组,饲养笼具安装有频闪仪（频率0.5 Hz）,笼具内装有发光二极管;FDM组豚鼠右眼用半透明眼罩遮盖,并确保豚鼠眼睑能正常活动;对照组豚鼠不予特殊处理。在造模第1天（0周）和第6周测量豚鼠右眼屈光度、眼轴长度和角膜曲率半径,并通过免疫荧光法观察S-opsin表达。结果 第0周,FLM、FDM组与对照组屈光度、眼轴长度、角膜曲率半径差异均无显著性（P > 0.05）。造模6周后,与对照组相比,FLM组、FDM组屈光度变化值、眼轴长度变化值差异均有显著性（P < 0.05）,而角膜曲率半径变化值差异无显著性（P=0.358）,提示成功建立近视模型。FLM组与FDM组相比,屈光度变化值、眼轴长度变化值、角膜曲率半径变化值差异均无显著性（P > 0.05）。免疫荧光结果显示：FLM组视蛋白灰度值>对照组视蛋白灰度值>FDM组视蛋白灰度值,任意两组进行比较,差异均有显著性（P < 0.001）。结论 频闪光和形觉剥夺均能建立近视模型,频闪光诱导性近视模型中S-opsin产生增加,而形觉剥夺性近视模型中S-opsin产生减少,说明两种近视模型的发生机制可能不同。