A local measure for modeling contrast discrimination: response to Katkov, Tsodyks and Sagi

Katkov, et al. [Katkov, M., Tsodyks, M., & Sagi, D. (2007). Singularities explained: Response to Klein. Vision Research, preceding article] commented on my comments [Klein, S. A. (2006). Separating transducer nonlinearities and multiplicative noise in contrast discrimination. Vision Research, 46, 4279-4293] regarding fitting the Kontsevich, et al. [Kontsevich, L. L., Chen, C. C., & Tyler, C. W. (2002). Separating the effects of response nonlinearity and internal noise psychophysically. Vision Research, 42, 1771-1784] contrast discrimination data. Klein [Klein, S. A. (2006). Separating transducer nonlinearities and multiplicative noise in contrast discrimination. Vision Research, 46, 4279-4293] focused on the question of whether the singularity associated with the constant noise model makes it difficult to reject that model. The present paper acknowledges the presence of a singularity but shows that even in the presence of a strong singularity and using a reasonable number of 2AFC trials, it is possible to not only reject the constant noise hypothesis, but also to place confidence limits on estimates of the magnitude of the multiplicative noise. Our analysis is based on measuring contrast discrimination among triplet of contrast levels.     

An overview of Leber congenital amaurosis: a model to understand human retinal development

Leber congenital amaurosis is a congenital retinal dystrophy described almost 150 years ago. Today, Leber congenital amaurosis is proving instrumental in our understanding of the molecular events that determine normal and aberrant retinal development. Six genes have been shown to be mutated in Leber congenital amaurosis, and they participate in a wide variety of retinal pathways: retinoid metabolism (RPE65), phototransduction (GUCY2D), photoreceptor outer segment development (CRX), disk morphogenesis (RPGRIP1), zonula adherens formation (CRB1), and cell-cycle progression (AIPL1). Longitudinal studies of visual performance show that most Leber congenital amaurosis patients remain stable, some deteriorate, and rare cases exhibit improvements. Histopathological analyses reveal that most cases have extensive degenerative retinal changes, some have an entirely normal retinal architecture, whereas others have primitive, poorly developed retinas. Animal models of Leber congenital amaurosis have greatly added to understanding the impact of the genetic defects on retinal cell death, and response to rescue. Gene therapy for RPE65 deficient dogs partially restored sight, and provides the first real hope of treatment for this devastating blinding condition.     

Beyond multiple pattern analyzers modeled as linear filters (as classical V1 simple cells): useful additions of the last 25 years

This review briefly discusses processes that have been suggested in the last 25 years as important to the intermediate stages of visual processing of patterns. Five categories of processes are presented: (1) Higher-order processes including FRF structures; (2) Divisive contrast nonlinearities including contrast normalization; (3) Subtractive contrast nonlinearities including contrast comparison; (4) Non-classical receptive fields (surround suppression, cross-orientation inhibition); (5) Contour integration.     

Bilateral periorbital necrotizing fasciitis following exposure to Holi colors: a case report

Holi festival is celebrated in India traditionally by applying colors on one another. Various ocular adverse effects of these colors have been reported including conjunctivitis and corneal abrasion. We report a case of bilateral periorbital necrotizing fasciitis, following exposure to Holi colors. General physicians might encounter more such cases after exposure to Holi colors. In India, these colors are prepared on a small scale and lack any quality checks. Use of such toxic colors should be discouraged, and all doctors should caution people against using synthetic dyes. This case report highlights the need to put manufacturing of Holi colors under guidelines of the Food and Drug Cosmetic Act and the Bureau of Indian Standards.     

Conjunctivitis due to Neisseria sicca: A case report

We report the first case, in Medline-based literature, of conjunctivitis caused by gram negative diplococcus, Neisseria sicca. Although it is not widely accepted as such, isolation from cultures of repeated eye swab samples suggests that N. sicca may be a pathogen in conjunctival infections. Positive culture for this organism should not be readily dismissed. Such conjunctivitis responded favorably to treatment with netilmicin eye drops.     

External Ophthalmomyiasis Presenting to an Emergency Department: Corneal Findings as a Sign of Oestrus ovis

Purpose

This study aims to determine the frequency of opthalmyomyiasis externa and the ocular findings of disease in Southern Khorasan.

Methods

All patients referred to the emergency department of Valiaser hospital during the year 2011 with external ophthalmomyiasis were enrolled in this study. The diagnosis of external ophthalmomyiasis was made according to clinical findings and the presence of Oestrus ovis larvae.

Results

There were 18 cases of external ophthalmomyiasis in the emergency department of Valiaser hospital in 2011. Most cases had the common signs and symptoms of allergic conjunctivitis, except for three males who were referred with respective complaints of red eye, foreign body sensation, and swelling around the eyelids after contact injury the previous day; corneal infiltration was present in three cases. The visual acuity among the three cases that had peripheral corneal involvement was 20 / 30 in both eyes. The bulbar conjunctiva showed chemosis in all cases and a ropy pattern discharge that was clinically compatible with external ophthalmomyiasis. However, in one case, microscopic slit lamp examination did not show Oestrus ovis larvae.

Conclusions

The frequency of external ophthalmomyiasis was high in this region. Although external ophthalmomyiasis usually manifests as allergic conjunctivitis, coronary-like corneal infiltration may be considered in the differential diagnosis of external ophthalmomyiasis or toxic insult.     

Simulation of artificial vision: I. Eccentric reading of isolated words,and perceptual learning

Simulations of artificial vision were performed to assess "minimum requirements for useful artificial vision". Retinal prostheses will be implanted at a fixed (and probably eccentric) location of the retina. To mimic this condition on normal observers, we projected stimuli of various sizes and content on a defined stabilised area of the visual field. In experiment 1, we asked subjects to read isolated 4-letter words presented at various degrees of pixelisation and at various eccentricities. Reading performance dropped abruptly when the number of pixels was reduced below a certain threshold. For central reading, a viewing area containing about 300 pixels was necessary for close to perfect reading (>90% correctly read words). At eccentricities beyond 10 degrees, close to perfect reading was never achieved even if more than 300 pixels were used. A control experiment using isolated letter recognition in the same conditions suggested that lower reading performance at high eccentricity was in part due to the "crowding effect". In experiment 2, we investigated whether the task of eccentric reading under such specific conditions could be improved by training. Two subjects, naive to this task, were trained to read pixelised 4-letter words presented at 15 degrees eccentricity. Reading performance of both subjects increased impressively throughout the experiment. Low initial reading scores (range 6%-23% correct) improved impressively (range 64%-85% correct) after about one month of training (about 1 h/day). Control tests demonstrated that the learning process consisted essentially in an adaptation to use an eccentric area of the retina for reading. These results indicate that functional retinal implants consisting of more than 300 stimulation contacts will be needed. They might successfully restore some reading abilities in blind patients, even if they have to be placed outside the foveal area. Reaching optimal performance may, however, require a significant adaptation process.     

Variations in the rheostat model of apoptosis: What studies of retinal ganglion cell death tell us about the functions of the Bcl2 family proteins

Studies of the functions of members of the Bcl2 gene family suggested that apoptosis was controlled by a rheostat in which anti-apoptotic proteins like BCL2 bound and sequestered pro-apoptotic proteins like BAX. Our current understanding of these proteins suggests that this is a simplistic model. The new rheostat model predicts that BH3-only peptides act as neutralizing ligands for the anti-apoptotic proteins, thus allowing molecules like BAX to become activated and initiate mitochondrial dysfunction - a critical step in the intrinsic apoptotic program. Studies of retinal ganglion cell apoptosis indicate that a threshold of BAX expression is required for its successful activation, which is independent of the overall concentration of anti-apoptotic proteins in these cells.     

Simulation of artificial vision: II. Eccentric reading of full-page text and the learning of this task

Reading of isolated words in conditions mimicking artificial vision has been found to be a difficult but feasible task. In particular at relatively high eccentricities, a significant adaptation process was required to reach optimal performances [Vision Res. 43 (2003) 269]. The present study addressed the task of full-page reading, including page navigation under control of subject's own eye movements. Conditions of artificial vision mimicking a retinal implant were simulated by projecting stimuli with reduced information content (lines of pixelised text) onto a restricted and eccentric area of the retina. Three subjects, na?ve to the task, were trained for almost two months (about 1 h/day) to read full-page texts. Subjects had to use their own eye movements to displace a 10 degrees x 7 degrees viewing window, stabilised at 15 degrees eccentricity in their lower visual field. Initial reading scores were very low for two subjects (about 13% correctly read words), and astonishingly high for the third subject (86% correctly read words). However, all of them significantly improved their performance with time, reaching close to perfect reading scores (ranging from 86% to 98% correct) at the end of the training process. Reading rates were as low as 1-5 words/min at the beginning of the experiment and increased significantly with time to 14-28 words/min. Qualitative text understanding was also estimated. We observed that reading scores of at least 85% correct were necessary to achieve 'good' text understanding. Gaze position recordings, made during the experimental sessions, demonstrated that the control of eye movements, especially the suppression of reflexive vertical saccades, constituted an important part of the overall adaptive learning process. Taken together, these results suggest that retinal implants might restore full-page text reading abilities to blind patients. About 600 stimulation contacts, distributed on an implant surface of 3 x 2 mm2, appear to be a minimum to allow for useful reading performance. A significant learning process will however be required to reach optimal performance with such devices, especially if they have to be placed outside the foveal area.     

Recruitment of marrow-derived endothelial cells to experimental choroidal neovascularization by local expression of vascular endothelial growth factor

PURPOSE: The question of whether adult animals maintain a reservoir of endothelial progenitor cells (EPCs) in the bone marrow that is involved in neovascularization is under investigation. The following study was undertaken to examine the potential contribution of EPCs to the development of choroidal neovascularization (CNV) in adult mice and to examine the role of local expression of vascular endothelial growth factor (VEGF) in this process. METHODS: Lethally irradiated, adult female nude mice were engrafted with whole bone marrow isolated from male transgenic mice expressing LacZ driven by the endothelial specific Tie-2 promoter. Two months, following bone marrow reconstitution, confirmed by quantitative Taqman PCR, an E1-deleted adenoviral vector expressing vascular endothelial growth factor (165) (Ad.VEGF(165)) was injected subretinally to induce CNV, confirmed by collagen IV immunohistochemistry. Bone marrow-derived endothelial cells were detected using either X-gal staining or Y chromosome in situ hybridization. Y chromosome positive cells within the CNV were confirmed to be endothelial cells by lectin staining. RESULTS: Subretinal Ad.VEGF(165) was capable of inducing CNV. Four-week old lesions were found to contain LacZ expressing cells within the CNV in bone marrow transplanted animals but not in negative control animals. Eighteen percent of all Y chromosome positive cells within the CNV were found to be lectin positive while 27% of all endothelial cells within the CNV were Y chromosome positive. CONCLUSION: Engrafted bone marrow-derived EPCs were shown to differentiate into endothelial cells at the site of subretinal VEGF-induced CNV in mice. These results suggest that EPCs contribute to the formation of neovascularization and that subretinal expression of VEGF might play an important role in recruitment of these cells to the site of CNV.     

A laminar cortical model for 3D perception of slanted and curved surfaces and of 2D images: development, attention, and bistability

A model of laminar visual cortical dynamics proposes how 3D boundary and surface representations arise from viewing slanted and curved 3D objects and 2D images. The 3D boundary representations emerge from non-classical receptive field interactions within intracortical and intercortical feedback circuits. Such non-classical interactions within cortical areas V1 and V2 contextually disambiguate classical receptive field responses to ambiguous visual cues using cells that are sensitive to colinear contours, angles, and disparity gradients. Remarkably, these cell types can all be explained as variants of a unified perceptual grouping circuit whose most familiar example is a 2D colinear bipole cell. Model simulations show how this circuit can develop cell selectivity to colinear contours and angles, how slanted surfaces can activate 3D boundary representations that are sensitive to angles and disparity gradients, how 3D filling-in occurs across slanted surfaces, how a 2D Necker cube image can be represented in 3D, and how bistable 3D Necker cube percepts occur. The model also explains data about slant aftereffects and 3D neon color spreading. It shows how chemical transmitters that habituate, or depress, in an activity-dependent way can help to control development and also to trigger bistable 3D percepts and slant aftereffects. Attention can influence which of these percepts is perceived by propagating selectively along object boundaries.     

BDNF-treated retinal progenitor sheets transplanted to degenerate rats: improved restoration of visual function

The aim of this study was to evaluate the functional efficacy of retinal progenitor cell (RPC) containing sheets with BDNF microspheres following subretinal transplantation in a rat model of retinal degeneration. Sheets of E19 RPCs derived from human placental alkaline phosphatase (hPAP) expressing transgenic rats were coated with poly-lactide-co-glycolide (PLGA) microspheres containing brain-derived neurotrophic factor (BDNF) and transplanted into the subretinal space of S334ter line 3 rhodopsin retinal degenerate rats. Controls received transplants without BDNF or BDNF microspheres alone. Visual function was monitored using optokinetic head-tracking behavior. Visually evoked responses to varying light intensities were recorded from the superior colliculus (SC) by electrophysiology at 60days after surgery. Frozen sections were studied by immunohistochemistry for photoreceptor and synaptic markers. Visual head tracking was significantly improved in rats that received BDNF-coated RPC sheets. Relatively more BDNF-treated transplanted rats (80%) compared to non-BDNF transplants (57%) responded to a "low light" intensity of 1cd/m2 in a confined SC area. With bright light, the onset latency of SC responses was restored to a nearly normal level in BDNF-treated transplants. No significant improvement was observed in the BDNF-only and no surgery transgenic control rats. The bipolar synaptic markers mGluR6 and PSD-95 showed normal distribution in transplants and abnormal distribution of the host retina, both with or without BDNF treatment. Red-green cones were significantly reduced in the host retina overlying the transplant in the BDNF-treated group. In summary, BDNF coating improved the functional efficacy of RPC grafts. The mechanism of the BDNF effects--either promoting functional integration between the transplant and the host retina and/or synergistic action with other putative humoral factors released by the RPCs--still needs to be elucidated.     

Arrestin migrates in photoreceptors in response to light: a study of arrestin localization using an arrestin-GFP fusion protein in transgenic frogs

Subcellular translocation of phototransduction proteins in response to light has previously been detected by immunocytochemistry. This movement is consistent with the hypothesis that migration is part of a basic cellular mechanism regulating photoreceptor sensitivity. In order to monitor the putative migration of arrestin in response to light, we expressed a functional fusion between the signal transduction protein arrestin and green fluorescent protein (GFP) in rod photoreceptors of transgenic Xenopus laevis. In addition to confirming reports that arrestin is translocated, this alternative approach generated unique observations, raising new questions regarding the nature and time scale of migration. Confocal fluorescence microscopy was performed on fixed frozen retinal sections from tadpoles exposed to three different lighting conditions. A consistent pattern of localization emerged in each case. During early light exposure, arrestin-GFP levels diminished in the inner segments (ISs) and simultaneously increased in the outer segments (OSs), initially at the base and eventually at the distal tips as time progressed. Arrestin-GFP reached the distal tips of the photoreceptors by 45-75 min at which time the ratio of arrestin-GFP fluorescence in the OSs compared to the ISs was maximal. When dark-adaptation was initiated after 45 min of light exposure, arrestin-GFP rapidly re-localized to the ISs and axoneme within 30 min. Curiously, prolonged periods of light exposure also resulted in re-localization of arrestin-GFP. Between 150 and 240 min of light adaptation the arrestin-GFP in the ROS gradually declined until the pattern of arrestin-GFP localization was indistinguishable from that of dark-adapted photoreceptors. This distribution pattern was observed over a wide range of lighting intensity (25-2700 lux). Immunocytochemical analysis of arrestin in wild-type Xenopus retinas gave similar results.