A5064918065- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- bioluminescence and chemiluminescence research
- Photochromic and Fluorescence Chemistry
- CRISPR and Genetic Engineering
- Neuroscience and Neural Engineering
- Developmental Biology and Gene Regulation
- Retinopathy of Prematurity Studies
- Ubiquitin and proteasome pathways
- Zebrafish Biomedical Research Applications
- Retinal Diseases and Treatments
- Olfactory and Sensory Function Studies
- RNA Research and Splicing
- Renal and related cancers
- interferon and immune responses
- Hedgehog Signaling Pathway Studies
- Ocular Disorders and Treatments
- Genomics and Chromatin Dynamics
- Connexins and lens biology
- Advanced biosensing and bioanalysis techniques
University of Southampton
2021-2022
University College London
2009-2021
Great Ormond Street Hospital
2017-2021
NIHR Great Ormond Street Hospital Biomedical Research Centre
2017-2021
University of Georgia
2006-2014
NeuroDevelopment Center
2012
Despite different aetiologies, age-related macular degeneration and most inherited retinal disorders culminate in the same final common pathway, loss of photoreceptors. There are few treatments none reverse vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. Recently, we demonstrated restoration vision following rod-photoreceptor into mouse model stationary night-blindness, raising critical question whether...
Abstract Loss of photoreceptors due to retinal degeneration is a major cause untreatable blindness. Cell replacement therapy, using pluripotent stem cell-derived photoreceptor cells, may be feasible future treatment. Achieving safe and effective cell critically dependent on the stringent selection purification optimal cells for transplantation. Previously, we demonstrated transplantation post-mitotic precursor labelled by fluorescent reporter genes. As genetically are not desirable here...
Loss of cone photoreceptors, crucial for daylight vision, has the greatest impact on sight in retinal degeneration. Transplantation stem cell-derived L/M-opsin cones, which form 90% human population, could provide a feasible therapy to restore vision. However, transcriptomic similarities between fetal and cones remain be defined, addition development cell purification strategies. Here, we report an analysis photoreceptor transcriptome using AAV2/9.pR2.1:GFP reporter. This led identification...
Retinal degenerative diseases are a major cause of untreatable blindness. Stem cell therapy to replace lost photoreceptors represents feasible future treatment. We previously demonstrated that postmitotic photoreceptor precursors expressing an NrlGFP transgene integrate into the diseased retina and restore some light sensitivity. As genetic modification precursor cells derived from stem cultures is not desirable for therapy, we have tested selection strategies using fluorochrome-conjugated...
Abstract The ciliary margin in lower vertebrates is a site of continual retinal neurogenesis and stem cell niche. By contrast, the human eye ceases neuron production before birth loss photoreceptors during life permanent major cause blindness. discovery proliferative population epithelium (CE) adult mammalian eye, designated cells, raised possibility that these cells could help to restore sight by replacing lost photoreceptors. We previously demonstrated feasibility photoreceptor...
Retinal degenerative disease causing loss of photoreceptor cells is the leading cause untreatable blindness in developed world, with inherited degeneration affecting 1 3000 people. Visual acuity deteriorates rapidly once cone photoreceptors die, as these provide daylight and colour vision. Here, proof-of-principle experiments, we demonstrate feasibility transplantation into wild-type degenerating retina two genetic models Leber congenital amaurosis, Crb1rd8/rd8 Gucy2e−/− mouse....
Loss of photoreceptor cells due to retinal degeneration is one the main causes blindness in developed world. Although there currently no effective treatment, cell replacement therapy using stem-cell-derived may be a feasible future treatment option. In order ensure safety and efficacy this approach, robust isolation purification protocols must developed. To end, we previously biomarker panel for mouse precursors from developing retina embryonic stem cultures. current study applied approach...
Ocular coloboma is a congenital defect resulting from failure of normal closure the optic fissure during embryonic eye development. This birth causes childhood blindness worldwide, yet genetic etiology poorly understood. Here, we identified novel homozygous mutation in SALL2 gene members consanguineous family affected with non-syndromic ocular variably affecting iris and retina. mutation, c.85G>T, introduces premature termination codon (p.Glu29*) predicted to truncate protein so that it...
Organoid cultures represent a unique tool to investigate the developmental complexity of tissues like human retina. NRL is transcription factor required for specification and homeostasis mammalian rod photoreceptors. In Nrl-deficient mice, photoreceptor precursor cells do not differentiate into rods, instead follow default pathway generate S-cone-like cells. To whether this genetic switch mechanism conserved in humans, we used CRISPR/Cas9 gene editing engineer an NRL-deficient embryonic stem...
Abstract Fluorescent reporter lines generated in human pluripotent stem cells are a highly useful tool to track, isolate, and analyze cell types lineages live cultures. Here, we generate the first cone photoreceptor line by CRISPR/Cas9 genome editing of embryonic (hESC) tag both alleles Guanine nucleotide-binding protein subunit gamma-T2 (GNGT2) gene with mCherry cassette. Three-dimensional optic vesicle-like structures were produced verify fidelity track cones throughout their development...
Retinitis pigmentosa (RP) is the most common cause of hereditary blindness, and may occur in isolation as a non-syndromic condition or alongside other features syndromic presentation. Biallelic monoallelic mutations one eight genes encoding pre-mRNA splicing factors are associated with RP. The molecular mechanism disease remains incompletely understood, limiting opportunities for targeted treatment. Here we use CRISPR base edited PRPF6 PRPF31 mutant cell lines, publicly-available data from...
Abstract The protocols described in this unit provide detailed information on how to isolate and expand, culture, ciliary epithelial cells (CECs), previously identified as retinal stem cells, from the adult mouse eye, embryonic progenitor (RPCs) developing retina. CECs are initially cultured floating conditions neurospheres then expanded monolayer cultures. RPCs conditions. Detailed for differentiation, well exogenous gene expression using lentivirus also described. Curr. Protoc. Stem Cell...