A5019159282- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Virus-based gene therapy research
- Neuroscience and Neural Engineering
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Retinal Diseases and Treatments
- Neural dynamics and brain function
- RNA regulation and disease
- Retinal and Optic Conditions
- Nerve injury and regeneration
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- bioluminescence and chemiluminescence research
- Herpesvirus Infections and Treatments
- Receptor Mechanisms and Signaling
- Advanced Fluorescence Microscopy Techniques
- Retinal and Macular Surgery
- Neuroscience and Neuropharmacology Research
- Photochromic and Fluorescence Chemistry
- Neuroinflammation and Neurodegeneration Mechanisms
- CCD and CMOS Imaging Sensors
- CAR-T cell therapy research
- Neurogenesis and neuroplasticity mechanisms
- Advanced biosensing and bioanalysis techniques
Institut de la Vision
2016-2025
Inserm
2016-2025
Sorbonne Université
2016-2025
Centre National de la Recherche Scientifique
2016-2025
Ruhr University Bochum
2022
Sorbonne University Abu Dhabi
2022
Centre hospitalier national d'ophtalmologie des Quinze-Vingts
2021
University of Pittsburgh
2021
Centre National pour la Recherche Scientifique et Technique (CNRST)
2019
École Pratique des Hautes Études
2018
Injection of a new gene therapy vector into the easily accessible vitreous transduced entire retina and rescued disease phenotypes.
Adeno-associated viral gene therapy has shown great promise in treating retinal disorders, with three promising clinical trials progress. Numerous adeno-associated virus (AAV) serotypes can infect various cells of the retina when administered subretinally, but detachment accompanying this injection induces changes that negatively impact microenvironment and survival neurons. Intravitreal administration could circumvent problem, only AAV2 from vitreous, transduction is limited to inner...
Adeno-associated virus serotype 2 (AAV2) has been shown to be effective in transducing inner retinal neurons after intravitreal injection several species. However, results nonprimates may not predictive of transduction the human retina, because differences eye size and specialized morphology high-acuity fovea. This was a study retina macaque, primate with ocular characteristics most similar that humans.In vivo imaging histology were used examine GFP expression macaque AAV vectors containing...
Background The pathologies of numerous retinal degenerative diseases can be attributed to a multitude genetic factors, and individualized treatment options for afflicted patients are limited cost-inefficient. In light the shared neurodegenerative phenotype among these disorders, safe broad-based neuroprotective approach would desirable overcome obstacles. As result, gene delivery secretable-neuroprotective factors Müller cells, type glia that contacts all classes neurons, represents an ideal...
Most inherited retinal dystrophies display progressive photoreceptor cell degeneration leading to severe visual impairment. Optogenetic reactivation of neurons mediated by adeno-associated virus (AAV) gene therapy has the potential restore vision regardless patient-specific mutations. The challenge for clinical translatability is a as close natural possible, while using surgically safe delivery route fragile degenerated retina. To preserve processing inner retina, we targeted ON bipolar...
Inherited retinal degeneration results from many different mutations in either photoreceptor-specific or nonphotoreceptor-specific genes. However, nearly all lead to a common blinding phenotype that initiates with rod cell death, followed by loss of cones. In most degenerations, other neuron types survive for long periods after blindness photoreceptor loss. One strategy restore light responsiveness retina rendered blind is express light-regulated ion channels transporters surviving neurons....
The natural tropism of most viral vectors, including adeno-associated (AAV) leads to predominant transduction neurons and epithelia within the central nervous system (CNS) retina. Despite clinical relevance glia for homeostasis in neural tissue, as causal contributors genetic disorders such Alzheimer's amyotrophic lateral sclerosis, efforts develop more efficient gene delivery vectors have met with limited success. Recently, vector engineering involving high-throughput random diversification...
Alternative splicing of nucleoredoxin-like 1 (Nxnl1) results in 2 isoforms the rod-derived cone viability factor. The truncated form (RdCVF) is a thioredoxin-like protein secreted by rods that promotes survival, while full-length isoform (RdCVFL), which contains thioredoxin fold, involved oxidative signaling and protection against hyperoxia. Here, we evaluated effects these different murine models rod-cone dystrophy. We used adeno-associated virus (AAV) to express mice found both systemic...
Research Article27 September 2016Open Access Transparent process Red-shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina Abhishek Sengupta INSERM, U968, Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, CNRS, UMR_7210, Search for more papers by this author Antoine Chaffiol Emilie Macé Romain Caplette Mélissa Desrosiers Maruša Lampič Valérie Forster Olivier Marre John Y Lin School of Medicine,...
The majority of inherited retinal degenerations converge on the phenotype photoreceptor cell death. Second- and third-order neurons are spared in these diseases, making it possible to restore light responses using optogenetics. Viral expression channelrhodopsin under ubiquitous promoters was previously shown visual function, albeit at intensities above illumination safety thresholds. Here, we report (to our knowledge, for first time) activation macaque retinas, up 6 months post-injection,...
The use of the visual system played a major role in elucidation molecular mechanisms controlling axonal regeneration injured CNS after trauma. In this model, CNTF was shown to be most potent known neurotrophic factor for optic nerve. To clarify downstream growth regulator Stat3, we analyzed and neuronal survival an nerve crush adult mice. infection retinal ganglion cells with adeno-associated virus serotype 2 (AAV2) containing wild-type (Stat3-wt) or constitutively active (Stat3-ca) Stat3...
Color vision is essential for an animal's survival. It starts in the retina, where signals from different photoreceptor types are locally compared by neural circuits. Mice, like most mammals, dichromatic with two cone types. They can discriminate colors only their upper visual field. In corresponding ventral however, cones display same spectral preference, thereby presumably impairing comparisons. this study, we systematically investigated retinal circuits underlying mouse color recording...
Intraocular injection of adeno-associated viral (AAV) vectors has been an evident route for delivering gene drugs into the retina. However, gaps in our understanding AAV transduction patterns within anatomically unique environments subretinal and intravitreal space primate eye impeded establishment noninvasive efficient delivery to foveal cones clinic. Here, we establish new vector-promoter combinations overcome limitations associated with AAV-mediated cone fovea supporting studies mouse...
A major challenge in the treatment of retinal degenerative diseases, with transplantation replacement photoreceptors, is difficulty inducing grafted cells to grow and maintain light sensitive outer segments host retina, which depends on proper interaction underlying pigment epithelium (RPE). Here, for an RPE-independent approach, we introduce a hyperpolarizing microbial opsin into photoreceptor precursors from newborn mice, transplant them blind mice lacking layer. These...
Abstract Vision restoration is an ideal medical application for optogenetics, because the eye provides direct optical access to retina stimulation. Optogenetic therapy could be used diseases involving photoreceptor degeneration, such as retinitis pigmentosa or age-related macular degeneration. We describe here selection, in non-human primates, of a specific optogenetic construct currently tested clinical trial. microbial opsin ChrimsonR, and showed that AAV2.7m8 vector had higher...
Retinal degenerative diseases caused by photoreceptor cell death are major causes of irreversible vision loss. As only primates have a macula, the nonhuman primate (NHP) models crucial role not in revealing biological mechanisms underlying high-acuity but also development therapies. Successful translation basic research findings into clinical trials and, moreover, approval first therapies for blinding inherited and age-related retinal dystrophies has been reported recent years. This article...