A5052477735- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- EEG and Brain-Computer Interfaces
- Advanced Fluorescence Microscopy Techniques
- Pluripotent Stem Cells Research
- Glaucoma and retinal disorders
- Zebrafish Biomedical Research Applications
- CRISPR and Genetic Engineering
- Ion channel regulation and function
- Advanced Memory and Neural Computing
- Receptor Mechanisms and Signaling
- Retinal Imaging and Analysis
- Visual perception and processing mechanisms
- Cell Image Analysis Techniques
- Renal and related cancers
- CCD and CMOS Imaging Sensors
- Retinal Diseases and Treatments
- Pain Mechanisms and Treatments
- Circadian rhythm and melatonin
- Optical Imaging and Spectroscopy Techniques
- Image Processing Techniques and Applications
- Nanoplatforms for cancer theranostics
Newcastle University
2016-2025
The Neurosciences Foundation
2013-2018
University of Newcastle Australia
2006
University of Edinburgh
2001
Washington University in St. Louis
2001
Smith-Kettlewell Eye Research Institute
1995-1996
National Institutes of Health
1989-1995
National Institute of Neurological Disorders and Stroke
1992-1995
Eunice Kennedy Shriver National Institute of Child Health and Human Development
1989-1990
Hebrew University of Jerusalem
1986
Abstract Mutations in pre-mRNA processing factors (PRPFs) cause autosomal-dominant retinitis pigmentosa (RP), but it is unclear why mutations ubiquitously expressed genes non-syndromic retinal disease. Here, we generate transcriptome profiles from RP11 ( PRPF31 -mutated) patient-derived organoids and pigment epithelium (RPE), as well Prpf31 +/− mouse tissues, which revealed that disrupted alternative splicing occurred for specific programmes. Mis-splicing of encoding proteins was limited to...
Recent successes in the stem cell field have identified some of key chemical and biological cues which drive photoreceptor derivation from human embryonic cells (hESC) induced pluripotent (hiPSC); however, efficiency this process is variable. We designed a three-step differentiation protocol combining previously published methods that direct hESC hiPSC toward retinal lineage, we further modified with additional supplements selected on basis reports eye development. report differentiating...
The availability of in vitro models the human retina which to perform pharmacological and toxicological studies is an urgent unmet need. An essential step for developing ability generate laminated, physiologically functional, light-responsive retinal organoids from renewable patient specific sources. We investigated five different human-induced pluripotent stem cell (iPSC) lines showed a significant variability their efficiency organoids. Despite this variability, by month 5 differentiation,...
DURING BRAIN DEVELOPMENT, THERE IS A PROGRESSIVE REDUCTION OF INTRACELLULAR CHLORIDE ASSOCIATED WITH SHIFT IN GABA POLARITY: depolarizes and occasionally excites immature neurons, subsequently hyperpolarizing them at later stages of development. This sequence, which has been observed in a wide range animal species, brain structures preparations, is thought to play an important role activity-dependent formation modulation functional circuits. sequence also considerably reinforced recently...
Abstract We and others have previously demonstrated that retinal cells can be derived from human embryonic stem (hESCs) induced pluripotent under defined culture conditions. While both cell types give rise to derivatives in the absence of inductive cues, this requires extended periods gives lower overall yield. Further understanding innate differentiation ability, identification key factors drive process, development clinically compatible conditions reproducibly generate functional neural...
During development, Gamma-aminobutyric acidergic (GABAergic) neurons mature at early stages, long before excitatory neurons. Conversely, GABA reuptake transporters become operative later than glutamate transporters. is therefore not removed efficiently from the extracellular domain and it can exert significant paracrine effects. Hence, GABA-mediated activity a prominent source of overall neural in developing CNS networks, while extend dendrites axons, establish synaptic connections. One...
Key points Novel pan‐retinal recordings of mouse retinal waves were obtained at near cellular resolution using a large‐scale, high‐density array 4096 electrodes to investigate changes in wave spatiotemporal properties from postnatal day 2 eye opening. Early cholinergic are large, slow and random, with low recruitment. A developmental shift GABA signalling depolarizing hyperpolarizing influences the dynamics waves. Glutamatergic that occur just before opening focused, faster, denser,...
We present a method for automated spike sorting recordings with high-density, large-scale multielectrode arrays. Exploiting the dense sampling of single neurons by multiple electrodes, an efficient, low-dimensional representation detected spikes consisting estimated spatial locations and dominant shape features is exploited fast reliable clustering into units. Millions events can be sorted in minutes, parallelized scales better than quadratically number spikes. Performance demonstrated using...
We report the development of a semiconductor nanorod-carbon nanotube based platform for wire-free, light induced retina stimulation. A plasma polymerized acrylic acid midlayer was used to achieve covalent conjugation nanorods directly onto neuro-adhesive, three-dimensional carbon surfaces. Photocurrent, photovoltage, and fluorescence lifetime measurements validate efficient charge transfer between films. Successful stimulation light-insensitive chick suggests potential use this novel in...
How a population of retinal ganglion cells (RGCs) encodes the visual scene remains an open question. Going beyond individual RGC coding strategies, results in salamander suggest that relative latencies pair encode spatial information. Thus, code based on this concerted spiking could be powerful mechanism to transmit information rapidly and efficiently. Here, we tested hypothesis mouse by recording simultaneous light-evoked responses from hundreds RGCs, at pan-retinal level, using new...
A major goal in the stem cell field is to generate tissues that can be utilized as a universal tool for vitro models of development and disease, drug development, or resource patients suffering from disease injury. Great efforts are being made differentiate human pluripotent cells toward retinal tissue, which akin native retina its cytoarchitecture function, yet numerous existing induction protocols remain variable their efficiency do not routinely produce morphologically functionally mature...
Abstract Hypoplastic left heart syndrome (HLHS) is a serious congenital cardiovascular malformation resulting in hypoplasia or atresia of the ventricle, ascending aorta, and aortic mitral valves. Diminished flow through side clearly key contributor to condition, but any myocardial susceptibility component as yet undefined. Using recent advances field induced pluripotent stem cells (iPSCs), we have been able generate an iPSC model HLHS characterize properties cardiac myocytes (CMs)...
Tissue specific extracellular matrices (ECM) provide structural support and enable access to molecular signals metabolites, which are essential for directing stem cell renewal differentiation. To mimic this phenomenon in vitro, tissue decellularisation approaches have been developed, resulting the generation of natural ECM scaffolds that comparable physical biochemical properties tissues currently gaining traction engineering regenerative therapies due ease standardised production, constant...
Abstract Death of photoreceptors is a common cause age-related and inherited retinal dystrophies, thus their replenishment from renewable stem cell sources highly desirable therapeutic goal. Human pluripotent cells provide useful source in view limitless self-renewal capacity potential to not only differentiate into the retina but also self-organize tissue with structure akin human as part three-dimensional organoids. Photoreceptor precursors have been isolated differentiating through...
Retinal dystrophies often lead to blindness. Developing therapeutic interventions restore vision is therefore of paramount importance. Here we demonstrate the ability pluripotent stem cell-derived cone precursors engraft and light responses in Pde6brd1 mouse, an end-stage photoreceptor degeneration model. Our data show that up 1.5% integrate into host retina, differentiate cones, close apposition bipolar cells. Half transplanted mice exhibited visual behavior these 33% showed binocular...
Retinal drug toxicity screening is essential for the development of safe treatment strategies a large number diseases. To this end, retinal organoids derived from human pluripotent stem cells (hPSCs) provide suitable platform due to their similarity retina and ease generation in large-scale formats. In study, two hPSC cell lines were differentiated organoids, which comprised all key types multiple nuclear synaptic layers. Single-cell RNA-Seq indicated maintenance ganglion bipolar cells: both...
Abstract Microglia are the primary resident immune cells in retina. They regulate neuronal survival and synaptic pruning making them essential for normal development. Following injury, they mediate adaptive responses under pathological conditions can trigger neurodegeneration exacerbating effect of a disease. Retinal organoids derived from human induced pluripotent stem (hiPSCs) increasingly being used range applications, including disease modelling, development new therapies study...
A novel, biophysically realistic model for early-stage, acetylcholine-mediated retinal waves is presented. In this model, neural excitability regulated through a slow after-hyperpolarization (sAHP) operating on two different temporal scales. As result, the simulated network exhibits competition between desynchronizing effect of spontaneous, cell-intrinsic bursts, and synchronizing synaptic transmission during waves. Cell-intrinsic bursts decouple activation sAHP current, we show that capable...
An emerging generation of high-density microelectrode arrays (MEAs) is now capable recording spiking activity simultaneously from thousands neurons with closely spaced electrodes. Reliable spike detection and analysis in such recordings challenging due to the large amount raw data dense sampling spikes Here, we present a highly efficient, online algorithm, an offline method improved rates, which enables estimation spatial event locations at resolution higher than that provided by array...
The choice of electrode material is paramount importance in neural prosthetic devices. Electrodes must be biocompatible yet able to sustain repetitive current injections a highly corrosive environment. We explored the suitability carbon nanotube (CNT) electrodes stimulate retinal ganglion cells (RGCs) mouse model outer degeneration. investigated morphological changes at bio-hybrid interface and RGC responses electrical stimulation following prolonged vitro coupling CNT electrodes. observed...
Abstract Induced pluripotent stem cell (iPSC)-derived retinal organoids provide a platform to study human retinogenesis, disease modeling, and compound screening. Although may represent tissue structures with greater physiological relevance the in vivo retina, their generation is not without limitations. Various protocols have been developed enable development of all major types; however, variability across iPSC lines often reported. Modulating signaling pathways important for eye formation,...