A5030588350- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Photoreceptor and optogenetics research
- CRISPR and Genetic Engineering
- Retinal and Optic Conditions
- Glaucoma and retinal disorders
- Connexins and lens biology
- Retinal Imaging and Analysis
- Retinal and Macular Surgery
- Ocular Diseases and Behçet’s Syndrome
- Retinopathy of Prematurity Studies
- Drug-Induced Ocular Toxicity
- Neuroscience and Neural Engineering
- Cellular transport and secretion
- RNA regulation and disease
- Pluripotent Stem Cells Research
- Virus-based gene therapy research
- Photochromic and Fluorescence Chemistry
- Phosphodiesterase function and regulation
- Ocular Disorders and Treatments
- Calpain Protease Function and Regulation
- Systemic Lupus Erythematosus Research
- Mitochondrial Function and Pathology
- Cell Adhesion Molecules Research
- Genetic and Kidney Cyst Diseases
Columbia University
2016-2025
Columbia University Irving Medical Center
2016-2025
NewYork–Presbyterian Hospital
2016-2025
New York Stem Cell Foundation
2018-2024
New York Hospital Queens
2014-2024
Presbyterian Hospital
2022-2023
Centre for Sight
2022
Stem Cell Institute
2022
Insall Scott Kelly Institute
2007-2020
Glaucoma Research Foundation
2010-2020
Basic fibroblast growth factor (FGF2) is a wide-spectrum mitogenic, angiogenic, and neurotrophic that expressed at low levels in many tissues cell types reaches high concentrations brain pituitary. FGF2 has been implicated multitude of physiological pathological processes, including limb development, angiogenesis, wound healing, tumor growth, but its role still unclear. To determine the function vivo , we have generated knockout mice, lacking all three isoforms, by homologous recombination...
Mutations in whole organisms are powerful ways of interrogating gene function a realistic context. We describe program, the Sanger Institute Mouse Genetics Project, that provides step toward aim knocking out all genes and screening each line for broad range traits. found hitherto unpublished were as likely to reveal phenotypes known genes, suggesting novel represent rich resource investigating molecular basis disease. many unexpected detected only because we screened them, emphasizing value...
Achromatopsia linked to variations in the CNGA3 gene is associated with day blindness, poor visual acuity, photophobia, and involuntary eye movements owing lack of cone photoreceptor function. No treatment currently available.To assess safety vision outcomes supplemental therapy adeno-associated virus (AAV) encoding (AAV8.CNGA3) patients CNGA3-linked achromatopsia.This open-label, exploratory nonrandomized controlled trial tested vector AAV8.CNGA3 administered by subretinal injection at a...
Heterotrimeric guanosine 5′-triphosphate (GTP)–binding proteins (G proteins) are deactivated by hydrolysis of the GTP that they bind when activated transmembrane receptors. Transducin, G protein relays visual excitation from rhodopsin to cyclic 3′,5′-monophosphate phosphodiesterase (PDE) in retinal photoreceptors, must be for light response recover. A point mutation γ subunit PDE impaired transducin-PDE interactions and slowed recovery rate flash transgenic mouse rods. These results indicate...
Background Variation in the ABCA4 gene is causal for, or associated with, a wide range of phenotypes from early onset Mendelian retinal dystrophies to late-onset complex disorders such as age-related macular degeneration (AMD). Despite substantial progress determining genetic variation, even complete sequencing entire open reading frame and splice sites identifies biallelic mutations only 60%–70% cases; 20%–25% remain with one mutation no are found 10%–15% cases clinically confirmed disease....
The U.S. Food and Drug Administration recently approved phase I/II clinical trials for embryonic stem (ES) cell-based retinal pigmented epithelium (RPE) transplantation, but this allograft transplantation requires lifelong immunosuppressive therapy. Autografts from patient-specific induced pluripotent (iPS) cells offer an alternative solution to problem. However, more data are required establish the safety efficacy of iPS in animal models before moving therapy into trials. This study...
To find all possible disease-associated variants in coding sequences of the ABCA4 gene a large cohort patients diagnosed with ABCA4-associated diseases.One hundred sixty-eight who had been clinically Stargardt disease, cone-rod dystrophy, and other phenotypes were prescreened for mutations microarray, resulting finding 1 2 expected 111 0 57 patients. The next-generation sequencing (NGS) strategy was applied to these sequence entire region splice sites gene. Identified new confirmed or...
Abstract Induced pluripotent stem cells (iPSCs) generated from patient fibroblasts could potentially be used as a source of autologous for transplantation in retinal disease. Patient-derived iPSCs, however, would still harbor disease-causing mutations. To generate healthy patient-derived cells, mutations might repaired with new gene-editing technology based on the bacterial system clustered regularly interspersed short palindromic repeats (CRISPR)/Cas9, thereby yielding grafts that require...
To improve the understanding of Stargardt disease by comparing structural changes seen on spectral domain optical coherence tomography (SD-OCT) to those visible fundus autofluorescence (FAF).
Autosomal recessive Stargardt disease (STGD1, MIM 248200) is caused by mutations in the ABCA4 gene. Complete sequencing of STGD patients identifies compound heterozygous or homozygous disease-associated alleles 65–70% and only one mutation 15–20% patients. This study was designed to find missing disease-causing variation a combination next-generation (NGS), array-Comparative Genome Hybridization (aCGH) screening, familial segregation silico analyses. The entire 140 kb genomic locus sequenced...
The hypothalamus is the central regulator of systemic energy homeostasis, and its dysfunction can result in extreme body weight alterations. Insights into complex cellular physiology this region are critical to understanding obesity pathogenesis; however, human hypothalamic cells largely inaccessible for direct study. Here, we developed a protocol efficient generation neurons from embryonic stem (ESCs) induced pluripotent (iPSCs) obtained patients with monogenetic forms obesity. Combined...
PURPOSE; The integrity of the inner segment ellipsoid (ISe) band, previously called segment/outer (IS/OS) border, seen on optical coherence tomography (OCT) scans is clinical significance. To better understand influence cones appearance this intensity its signal in patients with diminished cone function was examined.Horizontal line through fovea 30 healthy controls, 10 achromatopsia (A), and six dystrophy (CD) were obtained frequency domain (fd) OCT. fdOCT borders segmented a computer-aided...
To demonstrate outer retinal tubulation (ORT) in various degenerative disorders.This was a retrospective review of the multimodal imaging 29 eyes 15 patients with dystrophies and inflammatory maculopathies manifesting ORT. The morphologic features ORT its evolution over time were analyzed using spectral-domain optical coherence tomography data.Outer identified as round or ovoid structures hyperreflective borders pattern dystrophy (six eyes), acute zonal occult retinopathy (five retinitis...
Massive parallel sequencing enables identification of numerous genetic variants in mutant organisms, but determining pathogenicity any one mutation can be daunting. The most commonly studied preclinical model retinitis pigmentosa called the "rodless" (rd1) mouse is homozygous for two mutations: a nonsense point (Y347X) and an intronic insertion leukemia virus (Xmv-28). Distinguishing which causes retinal degeneration still under debate nearly century after discovery this organism. Here, we...
Purpose: We evaluated the incongruous observation whereby flecks in recessive Stargardt disease (STGD1) can exhibit increased short-wavelength autofluorescence (SW-AF) that originates from retinal pigment epithelium (RPE) lipofuscin, while near-infrared AF (NIR-AF), emitted primarily RPE melanin, is usually reduced or absent at fleck positions. Methods: Flecks SW- and NIR-AF images spectral-domain optical coherence tomography (SD-OCT) scans were studied 19 STGD1 patients carrying...