233 research outputs found
A biophysical model explains the spontaneous bursting behavior in the developing retina
During early development, waves of activity propagate across the retina and
play a key role in the proper wiring of the early visual system. During the
stage II these waves are triggered by a transient network of neurons, called
Starburst Amacrine Cells (SACs), showing a bursting activity which disappears
upon further maturation. While several models have attempted to reproduce
retinal waves, none of them is able to mimic the rhythmic autonomous bursting
of individual SACs and reveal how these cells change their intrinsic properties
during development. Here, we introduce a mathematical model, grounded on
biophysics, which enables us to reproduce the bursting activity of SACs and to
propose a plausible, generic and robust, mechanism that generates it. The core
parameters controlling repetitive firing are fast depolarizing -gated
calcium channels and hyperpolarizing -gated potassium channels. The
quiescent phase of bursting is controlled by a slow after hyperpolarization
(sAHP), mediated by calcium-dependent potassium channels. Based on a
bifurcation analysis we show how biophysical parameters, regulating calcium and
potassium activity, control the spontaneously occurring fast oscillatory
activity followed by long refractory periods in individual SACs. We make a
testable experimental prediction on the role of voltage-dependent potassium
channels on the excitability properties of SACs and on the evolution of this
excitability along development. We also propose an explanation on how SACs can
exhibit a large variability in their bursting periods, as observed
experimentally within a SACs network as well as across different species, yet
based on a simple, unique, mechanism. As we discuss, these observations at the
cellular level have a deep impact on the retinal waves description.Comment: 25 pages, 13 figures, submitte
Advantages and uses of the european network of veterinary ophthalmology and animal vision (REOVVA)in pigmentary retinopathies
In pigmentary retinopathies (Retinitis Pigmentosa), an alteration of peripheral vision is associated with
a deficit of night vision, followed by a loss of diurnal vision leading to blindness. These diseases are
found in both man and dogs, and are characterised by clinical, genetic, cellular and molecular heterogeneity.
Therapeutic and rehabilitation strategies for the management of these patients include
gene therapy, neuroprotection and retinal prosthesis. Developed in laboratory animals, the therapeutic
tools were validated in preclinical trials carried out in dogs. The European Network of Veterinary
Ophthalmology and Animal Vision (REOVVA) operates like a centre of clinical investigation combining
its skills with those of researchers and physicians from the Institute of Vision, bringing mutual benefits
to the treatment of man and animals, the latter being considered as proper patients.Les rétinopathies pigmentaires
(Retinitis Pigmentosa) sont des affections caractérisées par une altération de la vision
périphérique, associée à un déficit de la vision nocturne et ensuite à une perte de la
vision diurne aboutissant à la cécité. Ce sont des maladies homologues au chien et à l'homme
caractérisées par une hétérogénéité clinique, génétique, cellulaire et moléculaire. Les
stratégies thérapeutiques et réhabilitatrices pour la prise en charge des patients atteints
par ces affections font appel à la thérapie génique, la neuro-protection et les prothÚses
rétiniennes. Mis au point chez l'animal de laboratoire, les outils thérapeutiques ont été
validés dans des essais précliniques chez le chien. Considérant le chien comme un véritable
patient, le Réseau Européen d'Ophtalmologie Vétérinaire et de Vision Animale (REOVVA)
fonctionne comme un centre d'investigation clinique unissant ses compétences avec celles des
chercheurs et des médecins de l'Institut de la Vision pour un bénéfice réciproque des
traitements de l'homme et de l'animal, considéré comme un patient à part entiÚre
Evidence for functional GABAA but not GABAC receptors on mouse cone photoreceptors
International audienc
A review of in vivo animal studies in retinal prosthesis research
Background: The development of a functional retinal prosthesis for acquired blindness is a great challenge. Rapid progress in the field over the last 15years would not have been possible without extensive animal experimentation pertaining to device design and fabrication, biocompatibility, stimulation parameters and functional responses. This paper presents an overview of in vivo animal research related to retinal prosthetics, and aims to summarize the relevant studies. Methods: A Pubmed search of the English language literature was performed. The key search terms were: retinal implant, retinal prosthesis, artificial vision, rat, rabbit, cat, dog, sheep, pig, minipig. In addition a manual search was performed based on references quoted in the articles retrieved through Pubmed. Results: We identified 50 articles relevant to in vivo animal experimentation directly related to the development of a retinal implant. The highest number of publications related to the cat (nâ=â18). Conclusion: The contribution of animal models to the development of retinal prosthetic devices has been enormous, and has led to human feasibility studies. Grey areas remain regarding long-term tissue-implant interactions, biomaterials, prosthesis design and neural adaptation. Animals will continue to play a key role in this rapidly evolving fiel
Incorporation of chromaffin granule membranes into large-size vesicles suitable for patch-clamp recording
AbstractIncubation of chromaffin granules with excess liposomes at pH 6.0 resulted in the formation of cell-size structures, which were purified by centrifugation on sucrose gradients. Experiments with fluorescein-labeled granules indicated incorporation of granule membrane to these structures. The preparation contained various vesicular structures with a diameter up to 15 ÎŒm. The largest elements were studied by the âpatch-clampâ technique. âCell-attachedâ and âwhole-cellâ recordings indicated the presence of currents corresponding to unitary conductances ranging from 100 to 500 pS
Photoreceptor degeneration: therapeutic strategies and new perspectives
Ocular diseases involving photoreceptor degeneration still lead to blindness. However, different therapeutic
strategies preserving vision have been validated recently, as in age-related macular degeneration
(ARMD) or Leber congenital amaurosis (LCA). In the latter, gene therapy was found to restore
vision in patients progressively losing eyesight due the loss of their photoreceptors. This major success
opened the way for many other forms of gene therapy to prevent blindness or even restore some
degree of sight. Optogenetic therapy is one such example, where a gene coding for a photosensitive
protein from algae or bacteria is introduced in the genome of a cell to restore some light perception
in the blind retina. Other therapeutic strategies rely on trophic factors, such as Ciliary
Neurotrophic factor (CNTF) or RdCVF (rod-derived cone viability factor), or calcium channel blockers.
Finally, stem cell transplantation is likely to provide new modes of treatment in a near future. These
therapeutic strategies therefore hold great promises for diseases leading to blindness and considered
as incurable.Les maladies oculaires avec
dégénérescence des photorécepteurs sont toujours à l'origine de cécités. Cependant,
différentes approches thérapeutiques ont récemment été validées pour préserver la vision,
comme dans les cas de la dégénérescence maculaire liée à l'ùge ou de l'amaurose congénitale
de Leber. Pour cette derniÚre maladie, la thérapie génique a permis de restaurer la vision
de patients perdant progressivement la vue à la suite de la dégénérescence de leurs
photorécepteurs. Ce succÚs majeur a ouvert la voie à de nombreuses autres formes de thérapie
génique pour prévenir la cécité ou restaurer une certaine vision par la thérapie
optogénétique. Dans ce dernier cas, un gÚne codant une protéine photosensible issue d'algues
ou de bactĂ©ries est introduit dans le gĂ©nome d'une cellule pour restaurer une perception Ă
la lumiÚre dans la rétine aveugle. D'autres approches thérapeutiques reposent sur les
facteurs trophiques comme le CNTF (ciliary neurotrophic factor) ou le RdCVF (rod-derived
cone viability factor), ou encore les inhibiteurs des canaux Ca2+. Enfin, la
transplantation de cellules souches est amenée à devenir un mode thérapeutique dans un futur
proche. Ces différentes approches offrent donc un grand espoir de traitement des maladies
entraßnant la cécité et considérées comme incurables
Eye and taurine
Taurine is the most abundant amino acid in retina. Although unclear, its role is mainly related to its powerful antioxidant properties. The taurine concentrations in tissues are regulated by an exogenous intake through the nutrition. This taurine intake is highly dependent on the function of taurine transporter. In addition, an endogenous synthesis accounts for the physiological taurine amounts. Previous studies had shown that taurine nutritional deprivation in cat was responsible for severe retinal damages at the photoreceptor layer. By discovering the taurine depletion was incriminated in the retinal toxicity of vigabatrin, we recently demonstrated in different models of retinal degeneration that taurine was involved in the retinal ganglion cells survival. Accordingly, Taurine may play a crucial role in the prevention of retinal degeneration such as retinopathies and glaucomas.La taurine est lâacide aminĂ© le plus abondant dans la rĂ©tine. Son rĂŽle, encore mal connu est essentiellement liĂ© Ă son pouvoir anti-oxydant. Sa concentration tissulaire dĂ©pend dâun apport nutritionnel en taurine exogĂšne et du fonctionnement de son transporteur. De plus, une synthĂšse endogĂšne de taurine participe au maintien de son taux physiologique. Dâanciennes Ă©tudes ont montrĂ© que la privation nutritionnelle de taurine chez le chat est responsable de dommages rĂ©tiniens graves, affectant la couche des photorĂ©cepteurs. En dĂ©couvrant que la toxicitĂ© du vigabatrin est liĂ©e Ă une dĂ©plĂ©tion en taurine, nous avons rĂ©cemment montrĂ© que la taurine participe Ă©galement Ă la survie des cellules ganglionnaires rĂ©tiniennes dans diffĂ©rents modĂšles de dĂ©gĂ©nĂ©rescence rĂ©tinienne. La taurine pourrait ainsi ĂȘtre impliquĂ©e dans la prĂ©vention des dĂ©gĂ©nĂ©rescences rĂ©tiniennes telles que les rĂ©tinopathies et les glaucomes
Multiplexed computations in retinal ganglion cells of a single type
In the early visual system, cells of the same type perform the same computation in different places of the visual field. How these cells code together a complex visual scene is unclear. A common assumption is that cells of a single-type extract a single-stimulus feature to form a feature map, but this has rarely been observed directly. Using large-scale recordings in the rat retina, we show that a homogeneous population of fast OFF ganglion cells simultaneously encodes two radically different features of a visual scene. Cells close to a moving object code quasilinearly for its position, while distant cells remain largely invariant to the object's position and, instead, respond nonlinearly to changes in the object's speed. We develop a quantitative model that accounts for this effect and identify a disinhibitory circuit that mediates it. Ganglion cells of a single type thus do not code for one, but two features simultaneously. This richer, flexible neural map might also be present in other sensory systems
Modeling the emergence of stage II retinal waves in immature retina
International audienceRetinal waves are spontaneous bursting activity propagating in the developping retina until vision is functional. In this work we propose a biophysical modelling of the mechanism that generates the spontaneous intrinsic cell-autonomous rhythmic bursting in Starbust Amacrine Cells (SACs), observed experimentally in [1] which is directly linked with the emergence of stage II retinal waves. We analyze this system from the dynamical system and bifurcation theory perspective
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