A5071434182- Lysosomal Storage Disorders Research
- Retinal Development and Disorders
- Adenosine and Purinergic Signaling
- Cellular transport and secretion
- Retinal Diseases and Treatments
- Glycogen Storage Diseases and Myoclonus
- Glaucoma and retinal disorders
- Herpesvirus Infections and Treatments
- Virus-based gene therapy research
- Animal Genetics and Reproduction
- Trypanosoma species research and implications
- Galectins and Cancer Biology
- Intraocular Surgery and Lenses
- Barrier Structure and Function Studies
- Hereditary Neurological Disorders
- Hormonal Regulation and Hypertension
- Ion Transport and Channel Regulation
- Tissue Engineering and Regenerative Medicine
- Aquaculture disease management and microbiota
- Circadian rhythm and melatonin
- Toxoplasma gondii Research Studies
- Glycosylation and Glycoproteins Research
- Migraine and Headache Studies
- Advanced Glycation End Products research
- Microbial infections and disease research
University of Missouri
2013-2022
San Diego Zoo Institute for Conservation Research
2017
University of Missouri Hospital
2017
Ericsson (United States)
2017
Saint Louis Zoo
2017
Missouri College
2010-2015
AAV-mediated gene transfer to ependymal cells in a dog model of Batten disease provides sustained enzyme replacement and delays onset.
Late-infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a hereditary neurological disorder characterized by progressive retinal degeneration and vision loss, cognitive motor decline, seizures, pronounced brain atrophy. This fatal pediatric disease caused mutations in the CLN2 gene which encodes lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Utilizing TPP1−/− Dachshund model of disease, studies were conducted to assess effects TPP1 replacement administered directly CNS on...
The CLN2 form of neuronal ceroid lipofuscinosis is a neurodegenerative disease that results from mutations in the TPP1 gene. Affected children exhibit progressive declines most neurological functions including vision. Functional are accompanied by brain and retinal atrophy. encodes soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Dachshunds with null mutation disorder very similar to human disease. Periodic infusion recombinant protein or single injection gene therapy vector into...
CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1, which encodes the enzyme tripeptidyl peptidase-1 (TPP1). Studies using canine model for this disorder demonstrated delivery of TPP1 to cerebrospinal fluid (CSF) by intracerebroventricular administration an AAV-TPP1 vector resulted substantial delays onset and progression prolongation life span. We hypothesized treatment may not deliver...
CLN2 disease is one of a group lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs). The results from mutations in TPP1 gene that cause an insufficiency or complete lack soluble enzyme tripeptidyl peptidase-1 (TPP1). involved protein degradation, and this accumulation protein-rich autofluorescent bodies numerous cell types including neurons throughout central nervous system retina. characterized primarily by progressive loss neurological functions vision as well...
To develop instrumentation and methods for thorough quantitative assessment of the pupillary light reflex (PLR) in dogs under varying stimulus conditions.The PLR was recorded normal Dachshunds using a custom system allowing full user control over intensity, color, duration. Chemical restraint protocols were compared to determine which protocol provided optimal baseline stability pupil size appropriate eye positioning. A series white stimuli increasing intensity used elicit constriction....
The neuronal ceroid lipofuscinoses (NCLs) are autosomal recessive lysosomal storage diseases characterized by progressive neurodegeneration and accumulation of autofluorescent material in the central nervous system other tissues. One most prominent clinical signs NCL is decline cognitive function. We previously described a frame shift mutation TPP1 miniature long-haired Dachshunds which causes an early-onset form analogous to classical late-infantile onset (CLN2) children. Dogs homozygous...
Abstract African black-footed cats ( Felis nigripes ) are endangered wild felids. One male and full-sibling female cat developed vision deficits mydriasis as early 3 months of age. The diagnosis early-onset progressive retinal atrophy (PRA) was supported by reduced direct consensual pupillary light reflexes, phenotypic presence degeneration, a non-recordable electroretinogram with negligible amplitudes in both eyes. Whole genome sequencing, conducted on two unaffected parents one affected...
CLN2 neuronal ceroid lipofuscinosis is a rare recessive hereditary retinal and neurodegenerative disease resulting from deleterious sequence variants in TPP1 that encodes the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Children with this disorder develop normally, but starting at 2-4 years of age begin to exhibit neurological signs visual deficits. Vision loss progresses blindness associated progressive degeneration impairment function. Similar function occur dog model null...
The aim of this study was to establish normal ophthalmic parameters for select diagnostic tests in American white pelicans (Pelecanuserythrorhynchos). Twenty-one zoo-housed were manually restrained noninvasive ocular testing and complete examination. Tear production quantification using the phenol red thread test (PRTT), fluorescein staining, intraocular pressure (IOP) evaluation performed. In addition, conjunctival aerobic bacterial culture culture-independent 16S rRNA amplicon sequencing...
CLN2 neuronal ceroid lipofuscinosis is a rare hereditary neurodegenerative disorder characterized by deleterious sequence variants in TPP1 that result reduced or abolished function of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1). Children with this experience progressive neurological decline and vision loss starting around 2-4 years age. Ocular disease retinal degeneration impaired culminating total vision. Similar pathology occurs canine model null variant TPP1. A study using dog was...
Objective To understand how progressive rod cone degeneration due to a mutation in CEP290 affects the pupillary light reflex (PLR) domestic cats. Animals studied Domestic cats identified as either normal wildtype (WT; n = 6), or homozygous for rdAc and having early stage retinal (stage 2, S2; 4), advanced (S4; 6). Methods The effect of on pupil size was measured over series 10-s pulses white chromatic lightly sedated with medetomidine. Results In WT cats, PLR characterized by pronounced...
CLN5 neuronal ceroid lipofuscinosis is a hereditary neurodegenerative disease characterized by progressive neurological decline, vision loss and seizures. Visual impairment in children with attributed to decline retinal function accompanied degeneration as well impaired central nervous system associated global brain atrophy. We studied visual pathology five Golden Retriever littermates homozygous for the allele previously identified breed. The dogs exhibited signs of pronounced 21-22 months...
A 11-year-old neutered male Labrador retriever-cross dog was presented to the University of Missouri-Columbia Veterinary Ophthalmology Service for subtle visual deficits. Indirect ophthalmoscopy revealed a smooth, bullous elevation in superior-temporal retina OU. Optical coherence tomography (OCT) performed OU showed inner retinal separation consistent with retinoschisis. Electroretinography (ERG) markedly reduced b-wave amplitudes more severely affected eye (OD) compared less (OS). The most...