A5010390796- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Retinal Diseases and Treatments
- Neuroscience and Neural Engineering
- Cellular transport and secretion
- Zebrafish Biomedical Research Applications
- Lysosomal Storage Disorders Research
- Neurobiology and Insect Physiology Research
- Visual perception and processing mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- Nicotinic Acetylcholine Receptors Study
- CRISPR and Genetic Engineering
- Glioma Diagnosis and Treatment
- Angiogenesis and VEGF in Cancer
- Glaucoma and retinal disorders
- Cancer, Hypoxia, and Metabolism
- Virus-based gene therapy research
- Pluripotent Stem Cells Research
- Memory and Neural Mechanisms
- Protease and Inhibitor Mechanisms
University College London
2010-2024
Institute of Ophthalmology
2024
Cell and Gene Therapy Catapult
2022
King's College London
2022
Moorfields Eye Hospital NHS Foundation Trust
2018
University College Hospital
2012
Wolfson Foundation
2008
IRCCS Ospedale San Raffaele
2007
At various stages of the visual system, responses are modulated by arousal. Here, we find that in mice this modulation operates as early first synapse from retina and even retinal axons. To measure activity awake, intact brain, imaged synaptic boutons axons superior colliculus. Their depended not only on vision but also running speed pupil size, regardless illumination. Arousal typically reduced their selectivity for direction orientation. Recordings optic tract revealed arousal modulates...
The use of human pluripotent stem cell-derived retinal cells for cell therapy strategies and disease modelling relies on the ability to obtain healthy organised tissue in sufficient quantities. Generating such is a lengthy process, often taking over 6 months culture, current approaches do not always generate large quantities major types required. We adapted our previously described differentiation protocol investigate stirred-tank bioreactors. used immunohistochemistry, flow cytometry...
Abstract The rd1 mouse with a mutation in the Pde6b gene was first strain of mice identified retinal degeneration. However, AAV-mediated supplementation only results structural preservation photoreceptors, and restoration photoreceptor-mediated a-wave, but not bipolar cell-mediated b-wave. Here we show that Gpr179 prevents full vision mice. Backcrossing C57BL6 reveals complete lack b-wave subset mice, consistent an autosomal recessive Mendelian inheritance pattern. We identify gene, which...
Age-related macular degeneration and other diseases result in the loss of light-sensing cone photoreceptors, causing irreversible sight impairment. Photoreceptor replacement may restore vision by transplanting healthy cells, which must form new synaptic connections with recipient retina. Despite recent advances, convincing evidence functional connectivity arising from transplanted human photoreceptors advanced retinal is lacking. Here, we show restoration visual function after...
The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage disorders characterized by general neurodegeneration and premature death. Sight loss is also a major symptom in NCLs, severely affecting the quality of life patients, but it not targeted effectively brain-directed therapies. Here we set out to explore therapeutic potential an ocular gene therapy treat sight NCL due deficiency transmembrane protein CLN6. We found that, although Cln6nclf mice presented mainly with...
In the adult central nervous system, endothelial and neuronal cells engage in tight cross-talk as key components of so-called neurovascular unit. Impairment this important relationship adversely affects tissue homeostasis, observed neurodegenerative conditions including Alzheimer's Parkinson's disease. development, influence neuroprogenitor on angiogenesis is poorly understood. Here, we show mouse that these interact intimately with growing retinal vascular network, identify a novel...
Abstract The operating mode of the visual system depends on behavioural states such as arousal 1,2 . This dependence is seen both in primary cortex 3–7 (V1) and subcortical brain structures receiving direct retinal input 4,8 Here we show that this effect arises early output retina. We first measured activity a region receives projections 9 , superficial superior colliculus (sSC), found strongly depended state. modulation was not mediated by feedback inputs from V1 it immune to inactivation....
Background and Purpose Angiogenesis is a pathological component of neovascular age‐related macular degeneration. Current therapies, although successful, are prone to high levels patient non‐response loss efficacy over time, indicating the need explore other therapeutic avenues. We have shown that an interaction between syndecan‐2 tyrosine phosphatase receptor CD148 (RTP Type J) results in ablation angiogenesis. Here we exploit this pathway develop peptide activator as therapy for...
Abstract Microglia have recently been associated with complex functionalities both in the brain and retina, including synaptic function plasticity. While investigating morphology, protein expression profile connectivity of microglia mouse outer we found that they closely resemble interneurons retina other species. We argue functional studies are needed to reveal whether also perform an interneuron-like role vision.
Abstract Macular degeneration is the leading cause of blindness in developed world. Whilst most patients lose sight owing to atrophic changes, no treatments currently exist that improve vision deficit due atrophy. Here, we identify loss lateral inhibition as a specific mechanism by which photoreceptor reduces visual function beyond area. We find this adaptive, and if modulated can function, making inhibitory circuits an unexpected therapeutic target for age related macular disorders.
Abstract Macular degeneration is a leading cause of blindness. Treatments to rescue vision are currently limited. Here, we study how loss central affects lateral feedback spared areas the human retina. We identify cone-driven gain control mechanism that reduces visual function beyond atrophic area in macular degeneration. This finding provides an insight into negative effects geographic atrophy on vision. Therefore, develop strategy restore this mechanism, through activation laterally...
Here we studied serotonin (5-HT) as key regulator of adult neural stem cell (ANSC) proliferation, since 5-HT and drugs increasing have been linked to increased neurogenesis in the dentate gyrus hippocampus. In our in-vitro model, cultured neurospheres derived from mouse hippocampus serum-free medium containing epidermal (EGF) type-2 fibroblast growth factor (FGF2). Under given conditions ANSC express tryptophane-hydroxylase (TPH). Consequently, production was confirmed by high pressure...