A5075781178- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Photoreceptor and optogenetics research
- Glaucoma and retinal disorders
- Retinal and Optic Conditions
- Retinal and Macular Surgery
- Neuroscience and Neural Engineering
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Intraocular Surgery and Lenses
- Retinal Imaging and Analysis
- Photochromic and Fluorescence Chemistry
- Corneal surgery and disorders
- RNA Interference and Gene Delivery
- Pluripotent Stem Cells Research
- Optical Coherence Tomography Applications
- Herpesvirus Infections and Treatments
- Ophthalmology and Visual Impairment Studies
- Retinopathy of Prematurity Studies
- Cerebrovascular and Carotid Artery Diseases
- Ocular Diseases and Behçet’s Syndrome
- Ocular Surface and Contact Lens
- Advanced Fluorescence Microscopy Techniques
- Ophthalmology and Eye Disorders
- bioluminescence and chemiluminescence research
Johns Hopkins Hospital
2016-2025
Johns Hopkins Medicine
2018-2025
Johns Hopkins University
2016-2025
University of Baltimore
2022-2025
Smith-Kettlewell Eye Research Institute
2019-2021
University of Oxford
2010-2020
Rayat Bahra University
2017-2019
King Khaled Eye Specialist Hospital
2018
Research to Prevent Blindness
2018
Moorfields Eye Hospital NHS Foundation Trust
2016-2017
A subretinal visual implant (Alpha IMS, Retina Implant AG, Reutlingen, Germany) was implanted in 29 blind participants with outer retinal degeneration an international multicenter clinical trial. Primary efficacy endpoints of the study protocol were a significant improvement activities daily living and mobility to be assessed by tasks, recognition mobility, or combination thereof. Secondary acuity/light perception and/or object (clinicaltrials.gov, NCT01024803). During up 12 months...
One strategy to restore vision in retinitis pigmentosa and age-related macular degeneration is cell replacement. Typically, patients lose when the outer retinal photoreceptor layer lost, so therapeutic goal would be at this stage of disease. It not currently known if a degenerate retina lacking nuclear cells allow survival, maturation, reconnection replacement photoreceptors, as prior studies used hosts with preexisting time treatment. Here, using murine model severe human no host rod...
Photoreceptor transplantation is a potential future treatment for blindness caused by retinal degeneration. restores visual responses in end-stage degeneration, but has also been assessed non-degenerate retinas. In the latter scenario, subretinal places donor cells beneath an intact host outer nuclear layer (ONL) containing photoreceptors. Here we show that are labelled with marker through cytoplasmic transfer-94±4.1% of apparently well-integrated both and markers. We detect occurrence...
Monitoring for and reporting potential cases of intraocular inflammation (IOI) in clinical practice despite limited occurrences trials, including experiences with relatively new intravitreal agents, such as brolucizumab, pegcetacoplan, or faricimab, helps balance benefits risks these agents.
Abstract Photoreceptor degeneration due to retinitis pigmentosa (RP) is a primary cause of inherited retinal blindness. cell-replacement may hold the potential for repair in completely degenerate retina by reinstating light sensitive cells form connections that relay information downstream layers. This study assessed therapeutic photoreceptor progenitors derived from human embryonic and induced pluripotent stem (ESCs iPSCs) using protocol suitable future clinical trials. ESCs iPSCs were...
To investigate fundus autofluorescence (AF) characteristics in the Abca4(-/-) mouse, an animal model for AMD and Stargardt disease, to correlate findings with functional, structural, biochemical assessments.Blue (488 nm) near-infrared (790 AF images were quantitatively qualitatively analyzed pigmented mice wild type (WT) controls vivo. Functional, assessments included electroretinography (ERG), light electron microscopic analysis, A2E quantification. All performed across age groups.In mice,...
The recent approval in the United States of first adeno-associated viral (AAV) vector for treatment an inherited retinal degeneration validates this approach many other diseases. A major limiting factor continues to be size restriction AAV transgene at under 5 kb. Stargardt disease is most prevalent form recessively blindness and caused by mutations ABCA4, gene that codes ATP-binding cassette transporter protein family member 4, which has a coding sequence length 6.8 Dual approaches increase...
BACKGROUND. In retinitis pigmentosa (RP), rod photoreceptors degenerate from 1 of many mutations, after which cones are compromised by oxidative stress. N-acetylcysteine (NAC) reduces damage and increases cone function/survival in RP models. We tested the safety, tolerability, visual function effects oral NAC patients.
Purpose: The Foundation Fighting Blindness (FFB) Consortium is a collaboration of 41 international clinical centers that manage patients affected with inherited retinal diseases (IRDs). annual gene poll was initiated in 2020 to capture the genetic cause disease IRD and associated practices sites. Data from 2022 are reported here. Methods: In 2022, academic, private practice, government ophthalmology clinics members were polled identify per-case causality list 387 syndromic nonsyndromic...
Optogenetic strategies to restore vision in patients who are blind from end-stage retinal degenerations aim render remaining cells light sensitive once photoreceptors lost. Here, we assessed long-term functional outcomes following subretinal delivery of the human melanopsin gene (OPN4) rd1 mouse model degeneration using an adeno-associated viral vector. Ectopic expression OPN4 a ubiquitous promoter resulted cellular depolarization and ganglion cell action potential firing. Restoration pupil...
There is much debate on the adeno-associated virus (AAV) serotype that best targets specific retinal cell types and route of surgical delivery-intravitreal or subretinal. This study compared three most efficacious AAV vectors known to date in a mouse model degeneration (rd1 mouse) macaque human explants. Green fluorescent protein (GFP) driven by ubiquitous promoter was packaged into capsids: AAV2/8(Y733F), AAV2/2(quad Y-F) AAV2/2(7m8). Overall, AAV2/2(7m8) transduced largest area retina...
The long-term outcome of neuroprotection as a therapeutic strategy for preventing cell death in neurodegenerative disorders remains unknown, primarily due to slow disease progression and the inherent difficulty assessing neuronal survival vivo. Employing murine model retinal disease, we demonstrate that ciliary neurotrophic factor (CNTF) confers life-long protection against photoreceptor degeneration. Repetitive imaging allowed intrinsically fluorescent cone photoreceptors be quantified...
Human retinal organoid transplantation could potentially be a treatment for degenerative diseases. How the recipient retina regulates survival, maturation, and proliferation of transplanted cells is unknown. We human organoid-derived into photoreceptor-deficient mice conducted histology single-cell RNA sequencing alongside time-matched cultured organoids. Unexpectedly, we observed that migrated all layers traveled long distances. Using an unbiased approach, identified these as astrocytes...
Many retinal gene therapy clinical trials require subretinal injections of small volumes adeno-associated viral (AAV) vector solutions in patients with dystrophies, using equipment not specifically designed for this purpose. We therefore evaluated an optimized injection system order to identify variables that might influence the rate and final dose delivered. An was assembled a 41G polytetrafluoroethylene tip therapy. Flow recorded at relevant infusion pressures (2–22 psi [14–152 kPa]),...
Background The efficiency of clinical trials for retinitis pigmentosa (RP) treatment is limited by the screening burden and lack reliable surrogate markers functional end points. Automated methods to determine visual acuity (VA) may help address these challenges. We aimed if VA could be estimated using confocal scanning laser ophthalmoscopy (cSLO) imaging deep learning (DL). Methods Snellen corrected cSLO were obtained retrospectively. Johns Hopkins University (JHU) dataset was used 10-fold...
To investigate the feasibility and to identify sources of experimental variability quantitative qualitative fundus autofluorescence (AF) assessment in mice.Blue (488 nm) near-infrared (790 AF imaging was performed various mouse strains disease models (129S2, C57Bl/6, Abca4(-/-), C3H-Pde6b(rd1/rd1), Rho(-/-), BALB/c mice) using a commercially available scanning laser ophthalmoscope. Gray-level analysis used explore factors influencing measurements.A contact lens avoided cataract development...
Adeno-associated viral vectors (AAV) have been shown to be safe in the treatment of retinal degenerations clinical trials. Thus, improving efficiency gene delivery has become increasingly important increase success In this study, structural domains different rAAV serotypes isolated from primate brain were combined create novel hybrid recombinant AAV serotypes, rAAV2/rec2 and rAAV2/rec3. The efficacy these assessed wild type mice two models degeneration (the Abca4−/− mouse which is a model...
We assessed genotype-phenotype correlations among the visual, auditory, and olfactory phenotypes of 127 participants with Usher syndrome (USH2) (n =80) or nonsyndromic autosomal recessive retinitis pigmentosa (ARRP) = 47) due to USH2A variants, using clinical data molecular diagnostics from Rate Progression in Related Retinal Degeneration (RUSH2A) study. truncating alleles were associated USH2 had a dose-dependent effect on hearing loss severity no visual within subgroup. A group missense an...