Institute Of La Vision

Sainte-Foy-lès-Lyon, France

Institute Of La Vision

Sainte-Foy-lès-Lyon, France
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Valeiras D.R.,Institute Of La Vision | Orchard G.,National University of Singapore | Ieng S.-H.,Institute Of La Vision | Benosman R.B.,Institute Of La Vision
Frontiers in Neuroscience | Year: 2016

Pose estimation is a fundamental step in many artificial vision tasks. It consists of estimating the 3D pose of an object with respect to a camera from the object's 2D projection. Current state of the art implementations operate on images. These implementations are computationally expensive, especially for real-time applications. Scenes with fast dynamics exceeding 30-60 Hz can rarely be processed in real-time using conventional hardware. This paper presents a new method for event-based 3D object pose estimation, making full use of the high temporal resolution (1 μs) of asynchronous visual events output from a single neuromorphic camera. Given an initial estimate of the pose, each incoming event is used to update the pose by combining both 3D and 2D criteria. We show that the asynchronous high temporal resolution of the neuromorphic camera allows us to solve the problem in an incremental manner, achieving real-time performance at an update rate of several hundreds kHz on a conventional laptop. We show that the high temporal resolution of neuromorphic cameras is a key feature for performing accurate pose estimation. Experiments are provided showing the performance of the algorithm on real data, including fast moving objects, occlusions, and cases where the neuromorphic camera and the object are both in motion. © 2016 Reverter Valeiras, Orchard, Ieng and Benosman.

Chalk M.,IST Austria | Marre O.,Institute Of La Vision | Tkacik G.,IST Austria
Advances in Neural Information Processing Systems | Year: 2016

In many applications, it is desirable to extract only the relevant aspects of data. A principled way to do this is the information bottleneck (IB) method, where one seeks a code that maximizes information about a 'relevance' variable, Y, while constraining the information encoded about the original data, X. Unfortunately however, the IB method is computationally demanding when data are high-dimensional and/or non-Gaussian. Here we propose an approximate variational scheme for maximizing a lower bound on the IB objective, analogous to variational EM. Using this method, we derive an IB algorithm to recover features that are both relevant and sparse. Finally, we demonstrate how kernelized versions of the algorithm can be used to address a broad range of problems with non-linear relation between X and Y. © 2016 NIPS Foundation - All Rights Reserved.

Yin L.,University of Rochester | Masella B.,University of Rochester | Dalkara D.,University of California at Berkeley | Dalkara D.,Institute Of La Vision | And 5 more authors.
Journal of Neuroscience | Year: 2014

The fovea dominates primate vision, and its anatomy and perceptual abilities are well studied, but its physiology has been little explored because of limitations of current physiological methods. In this study, we adapted a novel in vivo imaging method, originally developed in mouse retina, to explore foveal physiology in the macaque, which permits the repeated imaging of the functional response of many retinal ganglion cells (RGCs) simultaneously. A genetically encoded calcium indicator, G-CaMP5, was inserted into foveal RGCs, followed by calcium imaging of the displacement of foveal RGCs from their receptive fields, and their intensity-response functions. The spatial offset of foveal RGCs from their cone inputs makes this method especially appropriate for fovea by permitting imaging of RGC responses without excessive light adaptation of cones. This new method will permit the tracking of visual development, progression of retinal disease, or therapeutic interventions, such as insertion of visual prostheses. © 2014 the authors.

Ortega M.C.,Hospital Nacional Of Paraplejicos | Cases O.,Institute Of La Vision | Merchan P.,Cincinnati Childrens Hospital Medical Center | Kozyraki R.,Institute Of La Vision | And 3 more authors.
GLIA | Year: 2012

Oligodendrocyte precursor cells (OPCs) of the optic nerve are generated in the preoptic area, from where they migrate to colonize it entirely. Sonic hedgehog (Shh) induces the proliferation of these cells as well as influencing their migration, acting through its canonical receptor (Ptc-1). However, the multiligand receptor megalin (or LRP-2) is also involved in Shh-induced OPC proliferation and migration, and thus, we have evaluated the relevance of this interaction. During the stages at which Shh influences OPC development, we found megalin to be selectively expressed by optic nerve astrocytes, whereas Ptc-1 and Gli1 were found in OPCs. Indeed, this pattern of expression paralleled the rostral-caudal expression of the three Shh-related molecules during the time course of plp-dm20 +-OPC colonization. The blockage of megalin partially abolished OPC chemoattraction and fully impaired Shh-induced proliferation. Using in vitro co-cultures of dissociated optic nerve cells, we demonstrated that Shh was internalized by astrocytes via megalin, and sufficient Shh was subsequently released to produce the biological effects on OPCs observed in the nerve. Together, these data indicate that at least part of the influence of Shh on OPCs is mediated by megalin during optic nerve development, and that astrocytes expressing megalin transiently capture Shh to present it to OPCs and/or to control the gradient of this molecule during development. © 2012 Wiley Periodicals, Inc.

Prabakaran T.,University of Aarhus | Nielsen R.,University of Aarhus | Larsen J.V.,University of Aarhus | Sorensen S.S.,Rigshospitalet | And 5 more authors.
PLoS ONE | Year: 2011

Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor, megalin, and sortilin and demonstrates their drug delivery capabilities for enzyme replacement therapy. Sortilin, a novel α-galactosidase A binding protein, reveals a predominant intracellular expression but also surface expression in the podocyte. The present study provides the rationale for the renal effect of treatment with α-galactosidase A and identifies potential pathways for future non-carbohydrate based drug delivery to the kidney podocyte and other potential affected organs. © 2011 Prabakaran et al.

Oliver V.F.,Johns Hopkins University | Wan J.,Johns Hopkins University | Agarwal S.,Ludwig Institute for Cancer Research | Agarwal S.,University of California at San Diego | And 4 more authors.
Epigenetics and Chromatin | Year: 2013

Background: Growing evidence suggests that DNA methylation plays a role in tissue-specific differentiation. Current approaches to methylome analysis using enrichment with the methyl-binding domain protein (MBD) are restricted to large (≥1 μg) DNA samples, limiting the analysis of small tissue samples. Here we present a technique that enables characterization of genome-wide tissue-specific methylation patterns from nanogram quantities of DNA. Results: We have developed a methodology utilizing MBD2b/MBD3L1 enrichment for methylated DNA, kinase pre-treated ligation-mediated PCR amplification (MeKL) and hybridization to the comprehensive high-throughput array for relative methylation (CHARM) customized tiling arrays, which we termed MeKL-chip. Kinase modification in combination with the addition of PEG has increased ligation-mediated PCR amplification over 20-fold, enabling >400-fold amplification of starting DNA. We have shown that MeKL-chip can be applied to as little as 20 ng of DNA, enabling comprehensive analysis of small DNA samples. Applying MeKL-chip to the mouse retina (a limited tissue source) and brain, 2,498 tissue-specific differentially methylated regions (T-DMRs) were characterized. The top five T-DMRs (Rgs20, Hes2, Nfic, Cckbr and Six3os1) were validated by pyrosequencing. Conclusions: MeKL-chip enables genome-wide methylation analysis of nanogram quantities of DNA with a wide range of observed-to-expected CpG ratios due to the binding properties of the MBD2b/MBD3L1 protein complex. This methodology enabled the first analysis of genome-wide methylation in the mouse retina, characterizing novel T-DMRs. © 2013 Oliver et al.; licensee BioMed Central Ltd.

Wahlin K.J.,Johns Hopkins University | Maruotti J.,Johns Hopkins University | Zack D.J.,Johns Hopkins University | Zack D.J.,Institute Of La Vision
Advances in Experimental Medicine and Biology | Year: 2014

Retinal degenerative disease involving photoreceptor (PR) cell loss results in permanent vision loss and often blindness. Generation of induced pluripotent stem cell (iPSC)-derived retinal cells and tissues from individuals with retinal dystrophies is a relatively new and promising method for studying retinal degeneration mechanisms in vitro. Recent advancements in strategies to differentiate human iPSCs (hiPSCs) into 3D retinal eyecups with a strong resemblance to the mature retina raise the possibility that this system could offer a reliable model for translational drug studies. However, despite the potential benefits, there are challenges that remain to be overcome before stem-cell-derived retinal eyecups can be routinely used to model human retinal diseases. This chapter will discuss both the potential of these 3D eyecup approaches and the nature of some of the challenges that remain. © Springer Science+Business Media, LLC 2014.

Wan J.,Johns Hopkins University | Oliver V.F.,Johns Hopkins University | Zhu H.,Johns Hopkins University | Zack D.J.,Johns Hopkins University | And 3 more authors.
Nucleic Acids Research | Year: 2013

The exact role of intragenic DNA methylation in regulating tissue-specific gene regulation is unclear. Recently, the DNA-binding protein CTCF has been shown to participate in the regulation of alternative splicing in a DNA methylation-dependent manner. To globally evaluate the relationship between DNA methylation and tissue-specific alternative splicing, we performed genome-wide DNA methylation profiling of mouse retina and brain. In protein-coding genes, tissue-specific differentially methylated regions (T-DMRs) were preferentially located in exons and introns. Gene ontology and evolutionary conservation analysis suggest that these T-DMRs are likely to be biologically relevant. More than 14% of alternatively spliced genes were associated with a T-DMR. T-DMR-associated genes were enriched for developmental genes, suggesting that a specific set of alternatively spliced genes may be regulated through DNA methylation. Novel DNA sequences motifs overrepresented in T-DMRs were identified as being associated with positive and/or negative regulation of alternative splicing in a position-dependent context. The majority of these evolutionarily conserved motifs contain a CpG dinucleotide. Some transcription factors, which recognize these motifs, are known to be involved in splicing. Our results suggest that DNA methylation-dependent alternative splicing is widespread and lay the foundation for further mechanistic studies of the role of DNA methylation in tissue-specific splicing regulation. © 2013 The Author(s). Published by Oxford University Press.

Ranganathan V.,Wilmer Eye Institute | Wahlin K.,Wilmer Eye Institute | Maruotti J.,Wilmer Eye Institute | Zack D.J.,Wilmer Eye Institute | And 2 more authors.
Nature Communications | Year: 2014

The repurposed CRISPR-Cas9 system has recently emerged as a revolutionary genome-editing tool. Here we report a modification in the expression of the guide RNA (gRNA) required for targeting that greatly expands the targetable genome. gRNA expression through the commonly used U6 promoter requires a guanosine nucleotide to initiate transcription, thus constraining genomic-targeting sites to GN 19 NGG. We demonstrate the ability to modify endogenous genes using H1 promoter-expressed gRNAs, which can be used to target both AN 19 NGG and GN 19 NGG genomic sites. AN 19 NGG sites occur ∼15% more frequently than GN 19 NGG sites in the human genome and the increase in targeting space is also enriched at human genes and disease loci. Together, our results enhance the versatility of the CRISPR technology by more than doubling the number of targetable sites within the human genome and other eukaryotic species. © 2014 Macmillan Publishers Limited.

Fauser S.,University of Cologne | Lambrou G.N.,Institute Of La Vision
Survey of Ophthalmology | Year: 2015

Anti-vascular endothelial growth factor (anti-VEGF) therapies for neovascular age-related macular degeneration (nAMD) have proven efficacy at a study-population level, although individual patient responses vary, with most of the patients responding well to anti-VEGF therapies, while a few respond poorly. The pathogenesis of AMD is known to have a genetic component, but it is unclear if any particular genotype can predict response to anti-VEGF therapy. With the advent of less expensive genotyping technology, there have been numerous studies within this area. Here we analyze potential biomarker candidates identified that could be used in a clinical setting to predict response to anti-VEGF treatment of nAMD. We analyze single nucleotide polymorphisms (SNPs) identified from 39 publications. The SNPs that appeared to be of most importance fell into two main groups: those previously associated with AMD pathogenesis and those within the signaling pathway targeted by anti-VEGF therapies. A number of small studies found evidence supporting an association between anti-VEGF treatment response and two SNPs, CFH rs1061170 and VEGFA rs699947, but results from randomized controlled trials found no such association. It is possible that, in the future, the cumulative effect of several high-risk SNPs may prove useful in a clinical setting and that other genetic biomarkers may emerge. © 2015 Elsevier Inc.

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