视网膜皮层图像信号处理的传输机制与仿真

侧抑制是神经系统普遍存在的机理。从侧抑制模型出发进行了视网膜处理及传输机制的研究,提出了基于差分方程的循环侧抑制动态数学模型。通过剖析视网膜感应细胞对光刺激的反应特性,阐述了视网膜皮层电脉冲信号的发放机制,指出了视网膜输出信号是以物体边缘信息为主体的传输机制。结合循环侧抑制动态数学模型,并考虑视网膜感应细胞对光刺激的适应性,创新性地进行了图像信号传递及处理的仿真模拟。     

用于活体人眼视网膜观察的自适应光学成像系统

利用自适应光学技术,研制了两套活体人眼视网膜高分辨力成像系统,在实时校正人眼波前误差的基础上,实现活体人眼视网膜细胞尺度的高分辨力成像。这两套系统分别采用19和37单元小型压电变形反射镜作为波前校正元件,哈特曼-夏克(Hartmann-Shack)波前传感器测量波前误差,用眼底反射的半导体激光作为波前探测的信标。在用计算机控制自适应光学系统实现人眼波前误差校正后,触发闪光灯照明视网膜,用CCD相机记录视网膜的高分辨力图像。校正后的残余波前误差的均方根值已分别小于1／6和1／10波长,相当于视网膜上成像分辨力分别为3．4μm和2．6μm,接近衍射极限。试验表明37单元系统的成像质量更好。     

Proteome Analysis of Aflibercept Intervention in Experimental Central Retinal Vein Occlusion

Aflibercept is a frequently used inhibitor of vascular endothelial growth factor (VEGF) in the treatment of macular edema following central retinal vein occlusion (CRVO). Retinal proteome changes following aflibercept intervention in CRVO remain largely unstudied. Studying proteomic changes of aflibercept intervention may generate a better understanding of mechanisms of action and uncover aspects related to the safety profile. In 10 Danish Landrace pigs, CRVO was induced in both eyes with an argon laser. Right eyes were treated with intravitreal aflibercept while left control eyes received isotonic saline water. Retinal samples were collected 15 days after induced CRVO. Proteomic analysis by tandem mass tag-based mass spectrometry identified a total of 21 proteins that were changed in content following aflibercept intervention. In retinas treated with aflibercept, high levels of aflibercept components were reached, including the VEGF receptor-1 and VEGF receptor-2 domains. Fold changes in the additional proteins ranged between 0.70 and 1.19. Aflibercept intervention resulted in a downregulation of pigment epithelium-derived factor (PEDF) (fold change = 0.84) and endoplasmin (fold change = 0.91). The changes were slight and could thereby not be confirmed with less precise immunohistochemistry and Western blotting. Our data suggest that aflibercept had a narrow mechanism of action in the CRVO model. This may be an important observation in cases when macular edema secondary to CRVO is resistant to aflibercept intervention.     

Dexamethasone Intravitreal Implant Is Active at the Molecular Level Eight Weeks after Implantation in Experimental Central Retinal Vein Occlusion

Central retinal vein occlusion (CRVO) is a visually disabling condition resulting from a thrombus in the major outflow vessel of the eye. The inflammatory response in CRVO is effectively treated with a dexamethasone (DEX) intravitreal implant. Uncovering the proteome changes following DEX implant intervention in CRVO may identify key proteins that mediate the beneficial effects of DEX. In six Göttingen minipigs, CRVO was induced in both eyes with an argon laser using a well-established experimental model. The right eyes were treated with a DEX intravitreal implant (Ozurdex, Allergan), while the left control eyes received a sham injection. Eight weeks after DEX intervention, retinal samples were collected and analyzed with tandem mass tag-based mass spectrometry. DEX implant intervention resulted in the upregulation of peptidyl-prolyl cis–trans isomerase FKBP5 (FKBP5) and ubiquilin-4. Immunohistochemistry showed expression of FKBP5 in the nuclei in all cellular layers of the retina. Cell adhesion molecule 3, tumor necrosis factor receptor superfamily member 16, and trans-1,2-dihydrobenzene-1,2-diol dehydrogenase were downregulated following DEX intervention. The upregulation of the corticosteroid-sensitive protein FKBP5 suggests that the implant remained active at the molecular level after eight weeks of treatment. Future studies may investigate if FKBP5 regulates the efficacy and duration of the DEX implant.     

A hybrid stochastic model of retinal angiogenesis

Understanding the biological principles that govern blood vessel growth in the retina has important clinical implications, for the prevention of possible retinopathies, which may eventually lead to blindness. The availability of a realistic mathematical model of the relevant phenomenon may support the medical community in both issues, diagnosis being related to inverse problems, and therapy to optimal control strategies. The mathematical modeling of retinal angiogenesis leads to an highly complex problem, because of dimension, nonlinearity, and intrinsic randomness. In this paper, we propose a reduced model which leads to numerical simulations that somehow reproduce normal vascularization and predict possible pathologies. We call our model hybrid because it includes the coupling of a fully stochastic model for the construction of a vessel network in the retina, with continuum underlying fields describing relevant factors, such as growth factors and oxygen. We perform numerical simulations of a stochastic particle system coupled with partial differential equations (PDEs)' so to obtain images of vessel structure resembling real retina vasculatures. We then derive a possible mean field approximation of the stochastic vessel network, so to obtain a fully deterministic PDE system for the evolution of the underlying fields. Actually, in order to reproduce the geometric structure of the retina vessel network, we have to keep a stochastic model (though simplified) for its construction. Future investigations may concern the use of such a mean field approximation in the numerical simulations of the retina vasculature. Inverse and optimal control problems being the final goal of our research plan.     

Optical Coherence Tomographic Features of Macular Diseases

Optical coherence tomography (OCT) is a new diagnostic technology which allows visualization of a cross-sectional image of the anterior eye and the retina in vivo with a high resolution similar to a histological section by light microscopy. Although the fundus can be examined at the semihistologic level by a biomicroscope, histopathologic study has been difficult because of the rare opportunity for retinal biopsy or enucleation. OCT reveals the intraretinal structure of macular diseases on the histopathologic level. In this article, we review the research on various macular diseases using OCT at Gunma University School of Medicine.     

Sodium dodecyl sulfate versus acid-labile surfactant gel electrophoresis: comparative proteomic studies on rat retina and mouse brain

A long-chain derivative of 1,3-dioxolane sodium propyloxy sulfate, with similar denaturing and electrophoretic properties as SDS, and facilitated protein identification following polyacrylamide gel electrophoresis (PAGE) for Coomassie-stained protein bands, has been tested. Comparative acid-labile surfactant/sodium dodecyl sulfate two-dimensional (ALS/SDS 2-D)-PAGE experiments of lower abundant proteins from the proteomes of regenerating rat retina and mouse brain show that peptide recovery for mass spectrometry (MS) mapping is significantly enhanced using ALS leading to more successful database searches. ALS may influence some procedures in proteomic analysis such as the determination of protein content and methods need to be adjusted to that effect. The promising results of the use of ALS in bioanalytics call for detailed physicochemical investigations of surfactant properties.     

An Integrated Circuit for Two-Dimensional Edge-Detection with Local Adaptation Based on Retinal Networks

We designed an integrated circuit for edge detection of a two-dimensional image based on the vertebrate outer retina, which has wide dynamic range in image processing. The unit circuit is simple, and operates as a current-mode analog metal-oxide-semiconductor (MOS) circuit. In order to extract edges from an image composed of bright and dark domains, the circuit realizes a function called local adaptation in which the sensitivity adapts to local brightness of the image. Simulation results, using the simulation program with integrated circuit emphasis (SPICE), of two-dimensional Gaussian-distributed images in which the intensity ranged over four orders of magnitude, showed the local adaptation. As a result, the intensity of output images was in the range of one order of magnitude. Furthermore, as the simulation result of real images, it was shown that edges in the dark domain, which was five times darker than the bright domain, were successfully detected as the bright domain in which input photocurrents ranged over two orders of magnitude.     

SYNAPTIC INPUTS FROM RODS AND CONES TO HORIZONTAL CELLS IN THE TIGER SALAMANDER RETINA

Synaptic inputs from rods and cones to horizontal cells (HCs) were studied in the flatmounted isolated retinas of the tiger salamander. Voltage-intensity relations, spectral sensitivities and response waveforms of the rod, the cone, and the HC under dark- and light-adapted conditions were examined. HCs receive mixed inputs from rods and cones in both dark- and light-adapted retinas. The relative rod/cone input in HC_s depends on the intensity of stimulus and background illumination, and it varies from HC to HC.     

Surface‐enhanced Raman spectra of melamine and other chemicals using a 1550 nm (retina‐safe) laser

Many trace chemical analyses are being transitioned from the lab to the field, among which is surface‐enhanced Raman spectroscopy. Although initial portable Raman analyzers primarily employ 785 nm laser excitation, recent studies suggest longer wavelengths, with an appropriate surface‐enhanced Raman‐active substrate, may provide equal sensitivity. Furthermore, 1550 nm excitation may provide added safety for the user, in that permanent retina damage does not occur. Here, we show that a reasonable enhancement factor can be obtained for melamine using 1550 nm laser excitation that is nearly equivalent to those obtained using 785 and 1064 nm laser excitation. We also demonstrate that a number of other chemicals of interest can be measured by 1550 nm surface‐enhanced Raman scattering, albeit only modest sensitivity is achieved because of instrument limitations, not enhancement factors. Copyright © 2011 John Wiley & Sons, Ltd.