A5024511512- Retinal Diseases and Treatments
- Retinal Development and Disorders
- Retinal Imaging and Analysis
- Glaucoma and retinal disorders
- Retinal and Optic Conditions
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA regulation and disease
- Single-cell and spatial transcriptomics
- Corneal Surgery and Treatments
- Retinopathy of Prematurity Studies
- Systemic Lupus Erythematosus Research
- CRISPR and Genetic Engineering
- Corneal surgery and disorders
- Pluripotent Stem Cells Research
- Ocular Diseases and Behçet’s Syndrome
- Molecular Biology Techniques and Applications
- Retinoids in leukemia and cellular processes
- Antioxidant Activity and Oxidative Stress
- Atherosclerosis and Cardiovascular Diseases
- Genetics, Bioinformatics, and Biomedical Research
- Calpain Protease Function and Regulation
- Proteoglycans and glycosaminoglycans research
- Retinal and Macular Surgery
- Advanced Fluorescence Microscopy Techniques
- Renal Diseases and Glomerulopathies
University of Iowa
2016-2025
University of Iowa Health Care
2024
Carver Bible College
2023
University of Iowa Hospitals and Clinics
2019-2021
University of Northern Iowa
2013
The human retina is a complex tissue responsible for detecting photons of light and converting information from these into the neurochemical signals interpreted as vision. Such visual signaling not only requires sophisticated interactions between multiple classes neurons, but also spatially-dependent molecular specialization individual cell types. In this study, we performed single-cell RNA sequencing on neural isolated both fovea peripheral in three donors. We recovered total 8,217 cells,...
Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many diseases, such as Best disease and male germ associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions the retina. While much known about distribution in retina, molecular components across posterior pole eye has not been well-studied. To investigate regional difference composition ocular tissues, we assessed differential gene expression temporal,...
To identify specific mutations causing North Carolina macular dystrophy (NCMD).Whole-genome sequencing coupled with reverse transcription polymerase chain reaction (RT-PCR) analysis of gene expression in human retinal cells.A total 141 members 12 families NCMD and 261 unrelated control individuals.Genome was performed on 8 affected individuals from 3 chromosome 6-linked (MCDR1) 2 5-linked (MCDR3). Variants observed the MCDR1 locus frequencies <1% published databases were confirmed using...
Single-cell RNA sequencing has revolutionized ocular gene expression studies. This technology enabled researchers to identify signatures for rare cell types and characterize how changes across biological conditions, such as topographic region or disease status. However, sharing single-cell results remains a major obstacle, particular individuals without computational background. To address these limitations, we developed Spectacle, an interactive web-based resource exploring previously...
Retinitis pigmentosa (RP) is a highly heterogeneous group of disorders characterized by degeneration the retinal photoreceptor cells and progressive loss vision. While hundreds mutations in more than 100 genes have been reported to cause RP, discovering causative many patients remains significant challenge. Exome sequencing an individual affected with non-syndromic RP revealed two plausibly disease-causing variants TRNT1, gene encoding nucleotidyltransferase critical for tRNA processing. A...
Abstract Age‐related macular degeneration ( AMD ) is a common, blinding disease of the elderly in which photoreceptor cells, retinal pigment epithelium and choriocapillaris endothelial cells ultimately degenerate. Recent studies have found that occurs early this cell drop‐out concomitant with increased deposition complement membrane attack complex MAC at choroidal endothelium. However, impact injury to poorly understood. To model event vitro , study downstream consequences injury, were...
Age-related macular degeneration (AMD) is a devastating disease characterized by central vision loss in elderly individuals. Previous studies have suggested link between elevated levels of total C-reactive protein (CRP) the choroid, CFH genotype, and AMD status; however, structural form CRP present its relationship to functional consequences not been assessed. In this report, we studied genotyped human donor eyes (n = 60) found that homozygous for high-risk (Y402H) allele had monomeric...
The glaucomas are a group of diseases characterized by optic nerve damage that together represent leading cause blindness in the human population and domestic animals. Here we report mutation LTBP2 causes primary congenital glaucoma (PCG) cats. We identified spontaneous form PCG cats established breeding colony segregating for consistent with fully penetrant, autosomal recessive inheritance trait. Elevated intraocular pressure, globe enlargement elongated ciliary processes were consistently...
Retinitis pigmentosa (RP) is a heterogeneous group of monogenic disorders characterized by progressive death the light-sensing photoreceptor cells outer neural retina. We recently identified novel hypomorphic mutations in tRNA Nucleotidyl Transferase, CCA-Adding 1 (TRNT1) gene that cause early-onset RP. To model this disease vitro, we generated patient-specific iPSCs and iPSC-derived retinal organoids from dermal fibroblasts patients with molecularly confirmed TRNT1-associated Pluripotency...
Abstract The human neural retina is a light sensitive tissue with remarkable spatial and cellular organization. Compared the periphery, central contains more densely packed cone photoreceptor cells unique morphologies synaptic wiring. Some regions of exhibit selective degeneration or preservation in response to retinal disease basis for this variation unknown. In study, we used both bulk single-cell RNA sequencing compare gene expression within concentric retina. We identified patterns...
PurposeTo investigate the distribution of genotypes and natural history ABCA4-associated retinal disease in a large cohort patients seen at single institution.DesignRetrospective, single-institution review.ParticipantsPatients University Iowa between November 1986 August 2022 clinically suspected to have caused by sequence variations ABCA4.MethodsDNA samples from participants were subjected tiered testing strategy progressing allele-specific screening whole genome sequencing. Charts...
Abstract Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the Western world. Although, majority stem cell research to date has focused on production retinal pigment epithelial (RPE) and photoreceptor cells for purpose evaluating disease pathophysiology replacement, there strong evidence that choroidal endothelial (CECs) form choriocapillaris vessels are first be lost this disease. As such, accurately evaluate develop an effective treatment,...
Prior to use, newly generated induced pluripotent stem cells (iPSC) should be thoroughly validated. While excellent validation and release testing assays designed evaluate potency, genetic integrity, sterility exist, they do not have the ability predict cell type-specific differentiation capacity. Selection of iPSC lines that limited capacity produce high-quality transplantable cells, places significant strain on valuable clinical manufacturing resources. The purpose this study was determine...
Abstract Mutations in ABCA4 are the most common cause of Mendelian retinal disease. Clinical evaluation this gene is challenging because its extreme allelic diversity, large fraction non-exomic mutations, and wide range associated We used patient-derived organoids as well DNA samples clinical data from a cohort patients with ABCA4-associated disease to investigate pathogenicity variant (IVS30 + 1321 A&gt;G) that occurs heterozygously 2% Europeans. found causes mis-splicing photoreceptor...
Structural and gene expression changes in the microvasculature of human choroid occur during normal aging age-related macular degeneration (AMD). In this study, we sought to determine impact AMD on endothelial cell glycoprotein CD34. Sections from 58 donor eyes were categorized as either young (under age 40), age-matched controls (> 60 without AMD), or affected (>age with early AMD, geographic atrophy, choroidal neovascularization). Dual labeling sections Ulex europaeus agglutinin-I lectin...
Introduction We retrospectively evaluated early-onset, autosomal recessive Stargardt disease in younger siblings from affected sibships using longitudinal analysis of visual acuity and multimodal imaging.
Abstract Stargardt disease, the most common inherited macular dystrophy, is characterized by vision loss due to central retinal atrophy. Although clinical trials for are currently underway, disease typically slowly progressive, and objective, imaging-based biomarkers critically needed. In this retrospective, observational study, we characterize thicknesses of individual sublayers optical coherence tomography (OCT) in a large cohort patients with molecularly-confirmed, ABCA4 -associated...