抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Many current neurophysiological, psychophysical, and psychological approaches to vision rest on the idea that when we see, the brain produces an internal representation of the world. The activation of this internal representation is assumed to give rise to the experience of seeing. The problem with this kind of approach is that it leaves unexplained how the existence of such a detailed internal representation might produce visual consciousness. An alternative proposal is made here. We propose that seeing is a way of acting. It is a particular way of exploring the environment. Activity in internal representations does not generate the experience of seeing. The outside world serves as its own, external, representation. The experience of seeing occurs when the organism masters what we call the governing laws of sensorimotor contingency. The advantage of this approach is that it provides a natural and principled way of accounting for visual consciousness, and for the differences in the perceived quality of sensory experience in the different sensory modalities. Several lines of empirical evidence are brought forward in support of the theory, in particular: evidence from experiments in sensorimotor adaptation, visual \"filling in,\" visual stability despite eye movements, change blindness, sensory substitution, and color perception.

A sensorimotor account of vision and visual consciousness-Authors' Response-Acting out our sensory experience

Amplitude decorrelation measurement is sensitive to transverse flow and immune to phase noise in comparison to Doppler and other phase-based approaches. However, the high axial resolution of OCT makes it very sensitive to the pulsatile bulk motion noise in the axial direction. To overcome this limitation, we developed split-spectrum amplitude-decorrelation angiography (SSADA) to improve the signal-to-noise ratio (SNR) of flow detection. The full OCT spectrum was split into several narrower bands. Inter-B-scan decorrelation was computed using the spectral bands separately and then averaged. The SSADA algorithm was tested on in vivo images of the human macula and optic nerve head. It significantly improved both SNR for flow detection and connectivity of microvascular network when compared to other amplitude-decorrelation algorithms.

/pdf/split-spectrum-amplitude-decorrelation-angiography-with-5066x1kwi2.pdf

Split-spectrum amplitude-decorrelation angiography with optical coherence tomography

Three-dimensional (3D) displays have become important for many applications including vision research, operation of remote devices, medical imaging, surgical training, scientific visualization, virtual prototyping, and more. In many of these applications, it is important for the graphic image to create a faithful impression of the 3D structure of the portrayed object or scene. Unfortunately, 3D displays often yield distortions in perceived 3D structure compared with the percepts of the real scenes the displays depict. A likely cause of such distortions is the fact that computer displays present images on one surface. Thus, focus cues-accommodation and blur in the retinal image-specify the depth of the display rather than the depths in the depicted scene. Additionally, the uncoupling of vergence and accommodation required by 3D displays frequently reduces one's ability to fuse the binocular stimulus and causes discomfort and fatigue for the viewer. We have developed a novel 3D display that presents focus cues that are correct or nearly correct for the depicted scene. We used this display to evaluate the influence of focus cues on perceptual distortions, fusion failures, and fatigue. We show that when focus cues are correct or nearly correct, (1) the time required to identify a stereoscopic stimulus is reduced, (2) stereoacuity in a time-limited task is increased, (3) distortions in perceived depth are reduced, and (4) viewer fatigue and discomfort are reduced. We discuss the implications of this work for vision research and the design and use of displays.

Vergence-accommodation conflicts hinder visual performance and cause visual fatigue.

Objective: To demonstrate optical coherence tomography for high-resolution, noninvasive imaging of the human retina. Optical coherence tomography is a new imaging technique analogous to ultrasound B scan that can provide cross-sectional images of the retina with micrometer-scale resolution. Design: Survey optical coherence tomographic examination of the retina, including the macula and optic nerve head in normal human subjects. Settings Research laboratory. Participants: Convenience sample of normal human subjects. Main Outcome Measures: Correlation of optical coherence retinal tomographs with known normal retinal anatomy. Results: Optical coherence tomographs can discriminate the cross-sectional morphologic features of the fovea and optic disc, the layered structure of the retina, and normal anatomic variations in retinal and retinal nerve fiber layer thicknesses with 10- μm depth resolution. Conclusion: Optical coherence tomography is a potentially useful technique for high depth resolution, cross-sectional examination of the fundus.

Optical Coherence Tomography of the Human Retina

We present the first scanning laser ophthalmoscope that uses adaptive optics to measure and correct the high order aberrations of the human eye. Adaptive optics increases both lateral and axial resolution, permitting axial sectioning of retinal tissue in vivo. The instrument is used to visualize photoreceptors, nerve fibers and flow of white blood cells in retinal capillaries.

Adaptive optics scanning laser ophthalmoscopy

Human colour vision depends on three classes of receptor, the short- (S), medium- (M), and long- (L) wavelength-sensitive cones. These cone classes are interleaved in a single mosaic so that, at each point in the retina, only a single class of cone samples the retinal image. As a consequence, observers with normal trichromatic colour vision are necessarily colour blind on a local spatial scale1. The limits this places on vision depend on the relative numbers and arrangement of cones. Although the topography of human S cones is known2,3, the human L- and M-cone submosaics have resisted analysis. Adaptive optics, a technique used to overcome blur in ground-based telescopes4, can also overcome blur in the eye, allowing the sharpest images ever taken of the living retina5. Here we combine adaptive optics and retinal densitometry6 to obtain what are, to our knowledge, the first images of the arrangement of S, M and L cones in the living human eye. The proportion of L to M cones is strikingly different in two male subjects, each of whom has normal colour vision. The mosaics of both subjects have large patches in which either M or L cones are missing. This arrangement reduces the eye's ability to recover colour variations of high spatial frequency in the environment but may improve the recovery of luminance variations of high spatial frequency.

The arrangement of the three cone classes in the living human eye

Henle's fiber layer (HFL) contains bundles of unmyelinated cone and rod photoreceptor axons terminating in the pedicles and spherules that synapse in the retinal outer plexiform layer (OPL).1 These fibers are intermingled with Muller cell processes and are obliquely oriented as a result of foveal pit development where photoreceptors migrate inward and ganglion cells migrate outward.2,3 Like axons elsewhere in the central nervous system, the axons of HFL contain microtubules and are long, cylindrical structures.1–3 Their average length is 558 μm,4 and the first synapses occur with dendrites of bipolar and horizontal cells approximately 350 μm from the foveal center.4 Given the large number of central foveal photoreceptor nuclei and this marked displacement, HFL constitutes a significant fraction of the thickness of retinal layers within the macula, as is evident histologically (Fig. 1). HFL is oriented radially about the fovea and is indirectly visible ophthalmoscopically in patients with macular star formation in neuroretinitis.5 HFL also demonstrates the optical property of form birefringence, a property that can be exploited to infer the location of the foveal center as a direct consequence of its consistent effects on polarized light.6



Figure 1.

Mammalian foveal histology, courtesy of Roger C. Wagner, Professor Emeritus of Biological Sciences, University of Delaware, http://dspace.udel.edu:8080/dspace/handle/19716/1884. Photoreceptor components are indicated by the rectangle, showing the substantial ...



Optical coherence tomography (OCT) uses infrared light to interferometrically derive optical reflectivity information varying by depth in living tissues.7 The use of broadband light sources, a spectrometer, and the application of signal processing techniques has culminated in commercial spectral domain (SD) OCT systems that are capable of imaging with a 5-μm axial resolution in retinal tissue.8,9 These improvements, along with acquisition speeds fast enough to permit frame averaging without significant motion artifact, contribute to improved image quality in SD-OCT devices capable of identifying structures that could not previously be resolved.10

Despite advances in SD-OCT hardware and software, HFL visualization has remained elusive. A seminal paper published in 2004 comparing in vitro OCT images of monkey fovea to histology recognized HFL as a major layer of the retina that could be visualized in vitro and that should be accounted for in vivo.11 However, since that publication, HFL has not been included in diagrams of retinal layers visualized by OCT, likely because of the inability to distinguish a change in reflectivity at the interface between the HFL and the outer nuclear layer (ONL).12–14 Furthermore, segmentation algorithms, normative thickness data, and ONL measurements overlying drusen have recently been published that do not recognize the contribution to macular thickness provided by HFL to the ONL.15–19 Although the need to account for the presence of HFL in OCT images has recently been recognized, the proposed means to measure the contribution of the HFL was an inferential normative model based on high-quality pathologic specimens rather than by a direct means of visualization (Curcio CA, et al. IOVS. 2010;51:ARVO E-Abstract 2286). The only explicit mention of the optical conditions in which HFL may be visualized with OCT can be found in a letter to the editor and was not experimentally validated.20 In our study we describe a systematic method that can be applied to commercial SD-OCT systems to directly visualize and quantify HFL. Additionally, we provide an optical explanation of this phenomenon and demonstrate its clinical relevance.

/pdf/revealing-henle-s-fiber-layer-using-spectral-domain-optical-37eepmw91b.pdf

Revealing Henle's Fiber Layer Using Spectral Domain Optical Coherence Tomography

Wave aberrations were measured with a Shack-Hartmann wavefront sensor (SHWS) in the right eye of a large young adult population when accommodative demands of 0, 3, and 6 D were presented to the tested eye through a Badal system. Three SHWS images were recorded at each accommodative demand and wave aberrations were computed over a 5-mm pupil (through 6th order Zernike polynomials). The accommodative response was calculated from the Zernike defocus over the central 3-mm diameter zone. Among all individual Zernike terms, spherical aberration showed the greatest change with accommodation. The change of spherical aberration was always negative, and was proportional to the change in accommodative response. Coma and astigmatism also changed with accommodation, but the direction of the change was variable. Despite the large inter-subject variability, the population average of the root mean square for all aberrations (excluding defocus) remained constant for accommodative levels up to 3.0 D. Even though aberrations change with accommodation, the magnitude of the aberration change remains less than the magnitude of the uncorrected aberrations, even at high accommodative levels. Therefore, a typical eye will benefit over the entire accommodative range (0-6 D) if aberrations are corrected for distance viewing.

A population study on changes in wave aberrations with accomodation

Inherited retinal degenerations represent a genetically heterogeneous group of diseases that include retinitis pigmentosa (RP) and Usher syndrome type 2. Retinal degenerations are characterized by slowly progressive death of rod and cone photoreceptors and relentless vision loss.1 One of the challenges that has hampered the development of treatments that may slow vision loss in retinal degeneration is the lack of sensitive outcome measures of disease progression.2 Objective, sensitive measures of photoreceptor survival may reduce the time required to identify a treatment effect of an experimental therapy.

Neurotrophic factors such as ciliary neurotrophic factor (CNTF) have shown promise in slowing the progression of retinal degeneration.3,4 Recent studies suggest CNTF can prevent and reverse secondary cone degeneration caused by a mutation in rhodopsin, a rod-specific gene.5 A phase 1 study6 of CNTF delivered by intravitreal implantation of a device containing encapsulated cells transfected with the human CNTF gene showed promising results in 10 patients with inherited retinal degeneration. Two phase 2 studies were initiated in patients with earlier (CNTF4; ClinicalTrials.gov number, NCT00447980) and later stage (CNTF3; ClinicalTrials.gov number, NCT00447993) inherited retinal degeneration. The objective of the CNTF4 study was to investigate whether CNTF treatment slows the loss of visual field sensitivity relative to the contralateral control eye over 24 months. However, natural history studies of retinal degeneration predict that significant changes in visual function may be measured reliably only after more than 7 years,7–9 suggesting that significant photoreceptor loss is necessary before changes in visual acuity function can be measured reliably. Outcome measures with greater sensitivity than standard measures of visual function can provide are urgently needed to assess photoreceptors during disease progression and in response to experimental treatments such as CNTF in eyes with retinal degeneration.

Standard clinical imaging techniques cannot visualize individual photoreceptors because of optical imperfections in living eyes. However, adaptive optics (AO) ophthalmoscopy, including adaptive optics scanning laser ophthalmoscopy (AOSLO), can produce images of individual cone photoreceptors noninvasively in living eyes.10–12 Direct visualization of cones allows comparison of cone spacing and density and, in ideal situations, tracking of individual cones longitudinally. Cone spacing and density have been used to characterize both normal eyes and eyes with retinal degeneration.11,13–20 However, they have not been used to track disease progression or response to treatment, including CNTF, in eyes with retinal degeneration.

We present the first images of individual cone photoreceptors observed longitudinally in normal eyes and in patients with inherited retinal degenerations during disease progression. We also report changes in cone photoreceptor structure in response to CNTF therapy in three patients with inherited retinal degenerations participating in the CNTF4 phase 2 clinical trial.

/pdf/longitudinal-study-of-cone-photoreceptors-during-retinal-49why58rfr.pdf

Austin Roorda

Papers

Adaptive optics scanning laser ophthalmoscopy

The arrangement of the three cone classes in the living human eye

Revealing Henle's Fiber Layer Using Spectral Domain Optical Coherence Tomography

A population study on changes in wave aberrations with accomodation

Longitudinal Study of Cone Photoreceptors during Retinal Degeneration and in Response to Ciliary Neurotrophic Factor Treatment