Lipid Nanoparticles Traverse Non-Corneal Path to Reach the Posterior Eye Segment: In Vivo Evidence

Lipid-based nanocarriers (LNs) have made it possible to prolong corneal residence time and improve the ocular bioavailability of ophthalmic drugs. In order to investigate how the LNs interact with the ocular mucosa and reach the posterior eye segment, we have formulated lipid nanocarriers that were designed to bear a traceable fluorescent probe in the present work. The chosen fluorescent probe was obtained by a conjugation reaction between fluoresceinamine and the solid lipid excipient stearic acid, forming a chemically synthesized adduct (ODAF, N-(3′,6′-dihydroxy-3-oxospiro [isobenzofuran-1(3H),9′-[9H] xanthen]-5-yl)-octadecanamide). The novel formulation (LN-ODAF) has been formulated and characterized in terms of its technological parameters (polydispersity index, mean particle size and zeta potential), while an in vivo study was carried out to assess the ability of LN-ODAF to diffuse through different ocular compartments. LN-ODAF were in nanometric range (112.7 nm ± 0.4), showing a good homogeneity and long-term stability. A TEM (transmission electron microscopy) study corroborated these results of characterization. In vivo results pointed out that after ocular instillation, LN ODAF were concentrated in the cornea (two hours), while at a longer time (from the second hour to the eighth hour), the fluorescent signals extended gradually towards the back of the eye. From the results obtained, LN-ODAF demonstrated a potential use of lipid-based nanoparticles as efficient carriers of an active pharmaceutical ingredient (API) involved in the management of retinal diseases.     

高速线扫描共焦检眼镜

高速线扫描共焦检眼镜使用线光束照明眼底视网膜,同时利用线阵CCD对视网膜平面的单次散射线光束探测成像。系统光学放大率为7倍,横向分辨率小于10μm,对于58kHz线频的1024pixel×512pixel成像模式,成像帧频高达110frame/s。该系统实现了高分辨率、高帧频模拟人眼实验图像的获取。     

Detection of small molecule concentration gradients in ocular tissues and humours

The eye is an elegant organ consisting of a number of tissues and fluids with specialised functions that together allow it to effectively transmit and transduce light input to the brain for visual perception. One key determinant of this integrated function is the spatial relationship of ocular tissues. Biomolecular distributions within the main ocular tissues cornea, lens, and retina have been studied extensively in isolation, yet the potential for metabolic communication between ocular tissues via the ocular humours has been difficult to visualise. To address this limitation, the current study presents a method to map spatial distributions of metabolites and small molecules in whole eyes, including ocular humours. Using a tape‐transfer system and freeze‐drying, the spatial distribution of ocular small molecules was investigated in mouse, rat, fish (black bream), and rabbit eyes using negative ion mode MALDI imaging mass spectrometry. Full‐scan imaging was used for discovery experiments, while MS/MS imaging for identification and localisation was also demonstrated. In all eyes, metabolites such as glutathione and phospholipids were localised in the main ocular tissues. In addition, in rodent eyes, major metabolites were distributed relatively uniformly in ocular humours. In contrast, both uniform and spatially defined ocular metabolite distributions were observed in the black bream eye. Tissue and ocular humour distributions were reproducible, as demonstrated by the three‐dimensional analysis of a mouse eye, and able to be captured with high spatial resolution analysis. The presented method could be used to further investigate the role of inter‐tissue metabolism in ocular health, and to support the development of therapeutics to treat major ocular diseases.     

The Effects of Prolonged Storage on ARPE-19 Cells Stored at Three Different Storage Temperatures

This study aimed to investigate how prolonged storage of adult retinal pigment epithelial (ARPE-19) cell sheets affects cell metabolism, morphology, viability, and phenotype. ARPE-19 cell sheets were stored at three temperatures (4 °C, 16 °C, and 37 °C) for three weeks. Metabolic status and morphology of the cells were monitored by sampling medium and examining cells by phase-contrast microscopy, respectively, throughout the storage period. Cell viability was analyzed by flow cytometry, and phenotype was determined by epifluorescence microscopy after the storage. Lactate production and glucose consumption increased heavily, while pH dropped considerably, through storage at 37 °C compared to 4 °C and 16 °C. During storage, morphology started to deteriorate first at 4 °C, then at 37 °C, and was maintained the longest at 16 °C. Viability of the cells after three weeks of storage was best preserved at 16 °C, while cells stored at 4 °C and 37 °C had reduced viability. Dedifferentiation indicated by reduced expression of retinal pigment epithelium-specific protein 65 (RPE65), zonula occludens protein 1 (ZO-1), and occludin after three weeks of storage was noticed in all experimental groups compared to control. We conclude that storage temperature affects the metabolic status of ARPE-19 cells and that 16 °C reduces metabolic activity while protecting viability and morphology.     

Foveal Pit Morphology Characterization: A Quantitative Analysis of the Key Methodological Steps

Disentangling the cellular anatomy that gives rise to human visual perception is one of the main challenges of ophthalmology. Of particular interest is the foveal pit, a concave depression located at the center of the retina that captures light from the gaze center. In recent years, there has been a growing interest in studying the morphology of the foveal pit by extracting geometrical features from optical coherence tomography (OCT) images. Despite this, research has devoted little attention to comparing existing approaches for two key methodological steps: the location of the foveal center and the mathematical modelling of the foveal pit. Building upon a dataset of 185 healthy subjects imaged twice, in the present paper the image alignment accuracy of four different foveal center location methods is studied in the first place. Secondly, state-of-the-art foveal pit mathematical models are compared in terms of fitting error, repeatability, and bias. The results indicate the importance of using a robust foveal center location method to align images. Moreover, we show that foveal pit models can improve the agreement between different acquisition protocols. Nevertheless, they can also introduce important biases in the parameter estimates that should be considered.     

新型红外测油仪中的光谱视网膜技术

将光谱视网膜技术应用于红外测油领域,研制出一种新的MFA-450型红外测油仪.介绍了所研制的超窄带、高透过率的中红外多波长滤光片和具有较高性能价格比、适合我国国情的红外热释电阵列检测器及相应检测电路和操作软件的开发.该仪器体积小、重量轻、无可动部件、稳定性好;测量精密度高(RSD<1％);灵敏度较现有同类仪器高1个数量级,检出限达到0.02mg/L(油/萃取剂);测量线性范围0.10～120.00mg/L,相关系数R2>0.999.     

眼固体生物力学研究

眼是光转换的视觉器官, 通常考虑将其作为一个生物力学结构. 眼睛是眼内肌和眼外肌产生压力的系统, 具有复杂的内血管系统,产生流体和溶合物的传导系统. 从生物力学角度看, 眼存在固体生物力学、流体生物力学和生物传输等问题. 本综述中, 介绍眼睛有意义的生物固体力学各方面研究成果及尚待解决的问题, 其研究对象为巩膜、角巩膜、角膜、视网膜、筛板以及眼调节和老花. 回顾测量巩膜力学性质和角巩膜应力－应变性质模型的有关研究成果, 然后论述这些研究成果的应用.巩膜力学另一重要应用是对近视的了解, 即眼的轴长过长使长距离光线不能够清晰聚焦于视网膜而引起近视. 角膜生物力学一个显著的应用是预测激光切开剖面手术, 它将使屈光角膜手术达到最优的术后视敏度. 筛板是眼中最具有生物力学研究兴趣的组织之一, 它是跨过巩膜管的多孔的结缔组织. 推导出青光眼的视神经病的力学理论.证据表明围绕着睫状肌的结蹄组织发生变化可能妨碍它的自由收缩的能力, 因此老花的病理学原因可能是多因素的.      

出血症香鱼眼睛组织结构变化的观察

用组织学和数理统计方法对香鱼眼睛的组织结构变化进行了观察和研究.结果表明：患病香鱼眼睛脉络膜血管壁细胞坏死脱落,红细胞部分崩解,数量减少;视网膜色素层增厚,并包围视杆细胞,视锥细胞膨大,数量减少;外核层、内核层细胞排列疏松;病鱼视网膜上外核层细胞核（O.N.）比神经节细胞（G.）的值为22.93±1.5,显著高于健康香鱼该比值（15.6±1.1,P〈0.05）.试验结果表明病鱼因患出血症其视觉结构发生了广泛的病理变化.     

基于视神经网络的混沌时间序列奇异信号实时检测算法

提出了一种基于视神经网络的实时检测混沌时间序列中的奇异点算法,设计了视神经网络奇异点检测器(RNNND);然后设计了基于反向传播(BP)神经网络和径向基函数(RBF)神经网络的混沌时间序列奇异点检测器.利用Lorenz理论模型产生的时间序列和实测输油管道压力时间序列分别检验了这3个奇异点检测器在抗干扰能力、检测微弱信号能力和运算速度等方面的性能.仿真和分析表明,RNNND具有良好的检测精度和较快检测速度.最后详细分析了3种奇异点检测器优缺点并给出了适用场合.     

Signal Formation of Image-Edge Motion Based on Biological Retinal Networks and Implementation into an Analog Metal-Oxide-Silicon Circuit

A simplified model was proposed for the formation of edge signals and generation of motion signals of a target based on the information processing mechanisms of outer and inner retinas of a vertebrate. Analog metal-oxide-silicon (MOS) integrated circuits were designed based on the model. Simulation program with integrated circuit emphasis (SPICE) simulation results showed the performance of local adaptation over a wide dynamic range in the outer retinal circuit and generation of the velocity signal of a moving edge in the inner retinal circuit. Preliminary experimental results showed local adaptation in a given input range in the outer retinal circuit and the generation of motion pulsed signals in the inner retinal circuit.