A5102979755- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Photoreceptor and optogenetics research
- Autophagy in Disease and Therapy
- Retinopathy of Prematurity Studies
- Genetic and Kidney Cyst Diseases
- Retinal and Macular Surgery
- Retinoids in leukemia and cellular processes
- Cellular transport and secretion
- Adenosine and Purinergic Signaling
- Retinal and Optic Conditions
- Retinal Imaging and Analysis
- Photochromic and Fluorescence Chemistry
- CRISPR and Genetic Engineering
- Connexins and lens biology
- Genetic Neurodegenerative Diseases
- Renal and related cancers
- Neurobiology and Insect Physiology Research
- Optical Coherence Tomography Applications
- melanin and skin pigmentation
- Neuroscience and Neuropharmacology Research
- Advanced Glycation End Products research
- Neuroscience and Neural Engineering
- RNA regulation and disease
- Diagnosis and treatment of tuberculosis
University of Michigan
2016-2025
Michigan Medicine
2022
Khyber Teaching Hospital
2022
Michigan United
2010-2021
W.K. Kellogg Foundation
2003-2020
Ann Arbor Center for Independent Living
2015
National Eye Institute
2004
Networks of transcriptional regulatory proteins dictate specification neural lineages from multipotent retinal progenitors. Rod photoreceptor differentiation requires the basic motif–leucine zipper (bZIP) transcription factor NRL, because loss Nrl in mice ( −/− ) results complete transformation rods to functional cones. To examine role NRL cell fate determination, we generated transgenic that express under control Crx promoter postmitotic precursors WT and retina. We show expression, both...
Autophagy regulates cellular homeostasis and response to environmental stress. Within the retinal pigment epithelium (RPE) of eye, level autophagy can change with both age disease. The purpose this study is determine relationship between reduced age-related degeneration RPE. gene encoding RB1CC1/FIP200 (RB1-inducible coiled-coil 1), a protein essential for induction autophagy, was selectively knocked out in RPE by crossing Best1-Cre mice which Rb1cc1 flanked Lox-P sites (Rb1cc1flox/flox). Ex...
Mutations in the genes necessary for structure and function of vertebrate photoreceptor cells are associated with multiple forms inherited retinal degeneration. gene encoding RHO (rhodopsin) a common cause autosomal dominant retinitis pigmentosa (adRP), Pro23His variant resulting misfolded protein that activates endoplasmic reticulum stress unfolded response. Stimulating macroautophagy/autophagy has been proposed as strategy clearing reducing death. We found retinas from mice heterozygous...
Nephronophthisis-related ciliopathies (NPHP-RCs) are developmental and degenerative kidney diseases that frequently associated with extrarenal pathologies such as retinal degeneration, obesity, intellectual disability. We recently identified mutations in a gene encoding the centrosomal protein SDCCAG8 causing NPHP type 10 humans. To study role of Sdccag8 disease pathogenesis, we generated gene-trap mouse line. Homozygous Sdccag8(gt/gt) mice lacked wild-type transcript protein, recapitulated...
CNGB3 encodes the beta-subunits of cyclic nucleotide-gated channels in photoreceptor plasma membrane. mutations cause a channelopathy that results impaired cone function manifesting achromatopsia. The clinical physiology and phenotype three affected sisters carriers were evaluated family with homozygous mutation an unrelated male harboring both CNGA3 mutations.Index patients screened for by DNA sequencing. Visual examination included acuity, color vision, Goldmann visual fields (GVF),...
Animal models of human disease are an invaluable component studies aimed at understanding pathogenesis and therapeutic possibilities. Mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR) most common cause X-linked (XLRP) estimated to 20% all retinal dystrophy cases. A majority RPGR mutations present ORF15, purine-rich terminal exon predominant splice-variant expressed retina. Here we describe genetic phenotypic characterization degeneration 9 (Rd9) strain mice, a...
Late-onset retinal macular degeneration (L-ORD) is an autosomal dominant inherited disorder caused by a single missense mutation (S163R) in the CTRP5/C1QTNF5 protein. Early phenotypic features of L-ORD include: dark adaptation abnormalities, nyctalopia, and drusen deposits peripheral region. Apart from posterior segment these patients also develop abnormally long anterior lens zonules. In sixth decade life rod cone function declines, accompanied electroretinogram (ERG) abnormalities. Some...
Purpose: The purpose of this study was to evaluate baseline best corrected visual acuity (BCVA), full-field electroretinography (ERG), stimulus thresholds (FST), and their relationship with demographic clinical characteristics in the Rate Progression Usher syndrome type 2 (USH2A)-related Retinal Degeneration (RUSH2A) multicenter study. Methods: Participants had (USH2, N = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP, 47) associated biallelic variants USH2A gene....
The orphan nuclear receptor NR2E3 is a direct transcriptional target of NRL, the key basic motif leucine zipper transcription factor that dictates rod versus cone photoreceptor cell fate in mammalian retina. lack function humans and retinal degeneration rd7 mutant mouse leads to increased S-cones accompanied by degeneration, whereas ectopic expression Nr2e3 cone-only Nrl−/− retina generates rod-like cells do not exhibit any visual function. Using GFP tag newborn rods 5-bromo-2′-deoxyuridine...
In addition to rods and cones, mammals have inner retinal photoreceptors called intrinsically photosensitive ganglion cells (ipRGCs), which use the photopigment melanopsin mediate nonimage-forming visual responses, such as pupil reflexes circadian entrainment. After photic activation, photopigments must be reverted their dark state light-sensitive again. For some extent regeneration depends on retinoid cycle in adjacent pigment epithelium (RPE). By contrast, ipRGCs are far from RPE, previous...
Retinal on-pathway dysfunction is implicated in human complete-type congenital stationary night blindness (CSNB1), a Mendelian genetic condition that results from mutations the NYX gene encoding protein nyctalopin. We probed cone pathway four genotyped CSNB1 affected males by electroretinogram (ERG) recordings elicited with photopic sinusoidal and rapid-on/off-ramp flicker stimuli are reputed to elicit on/off-pathway activity selectively. Results were analyzed relation ERG abnormalities...
purpose. To characterize a canine model of autosomal recessive RP due to PDE6A gene mutation. methods. Affected and breed- age-matched control puppies were studied by electroretinography (ERG), light electron microscopy, immunohistochemistry, assay for retinal PDE6 levels enzymatic activity. results. The mutant failed develop normal rod-mediated ERG responses had reduced light-adapted a-wave amplitudes from an early age. residual waveforms originated primarily cone-driven responses....
Autophagy is a lysosomal degradation pathway critical to preventing the accumulation of cytotoxic proteins. Deletion essential autophagy gene Atg5 from rod photoreceptors retina (atg5Δrod mouse) results in phototransduction protein transducin and degeneration these neurons. The purpose this study test hypothesis that autophagic visual transduction proteins prevents retinal degeneration. Targeted deletion both Gnat1 (a encoding α subunit heterotrimeric G-protein transducin) resulted...
Neurodegeneration is a central aspect of the early stages diabetic retinopathy, primary ocular complication associated with diabetes. While progress has been made to improve vascular perturbations there are still no treatment options counteract neuroretinal degeneration Our previous work suggested that molecular chaperones α-crystallins could be involved in pathophysiology retinopathy; however, role and regulation remained unknown. In present study, we demonstrated neuroprotective...
Patients with inherited retinal dystrophies (IRDs) were recruited from two understudied populations: Mexico and Pakistan as well a third well-studied population of European Americans to define the genetic architecture IRD by performing whole-genome sequencing (WGS). Whole-genome analysis was performed on 409 individuals 108 unrelated pedigrees IRDs. All patients underwent an ophthalmic evaluation establish phenotype. Although in this study had previously been examined for mutations known...
Background Advanced age contributes to clinical manifestations of many retinopathies and represents a major risk factor for age-related macular degeneration, leading cause visual impairment blindness in the elderly. Rod photoreceptors are especially vulnerable genetic defects changes microenvironment, among first neurons die normal aging retinal degenerative diseases. The molecular mechanisms underlying rod photoreceptor vulnerability potential biomarkers process this highly specialized cell...
Expansion of a CAG repeat in ATXN3 causes the dominant polyglutamine disease spinocerebellar ataxia type 3 (SCA3), yet physiological role remains unclear. Here, we focus on unveiling function Ataxin-3 (ATXN3) retina, neurological organ amenable to morphological and studies. Depletion Atxn3 zebrafish mice functional retinal alterations and, more precisely, photoreceptor cilium outer segment elongation, cone opsin mislocalization, hyperexcitation. localizes at basal body axoneme cilium,...
Purpose: Mutations in USH2A gene are responsible for the greatest proportion of Usher Syndrome (USH) population, among which more than 30% frameshift mutations on exon 13. A clinically relevant animal model has been absent USH2A-related vision loss. Here we sought to establish a rabbit carrying mutation 12 (human 13 equivalent). Methods: CRISPR/Cas9 reagents targeting were delivered into embryos produce an mutant line. The knockout animals subjected series functional and morphological...