A5019070349- Multiple Sclerosis Research Studies
- Sirtuins and Resveratrol in Medicine
- Retinal Development and Disorders
- Glaucoma and retinal disorders
- Cerebral Venous Sinus Thrombosis
- Retinal and Optic Conditions
- Neuroinflammation and Neurodegeneration Mechanisms
- Herpesvirus Infections and Treatments
- Ophthalmology and Eye Disorders
- Ocular Diseases and Behçet’s Syndrome
- Animal Virus Infections Studies
- SARS-CoV-2 and COVID-19 Research
- Retinal Diseases and Treatments
- Peripheral Neuropathies and Disorders
- Systemic Lupus Erythematosus Research
- Retinopathy of Prematurity Studies
- Corneal Surgery and Treatments
- RNA Interference and Gene Delivery
- interferon and immune responses
- Neurological Disorders and Treatments
- Cell death mechanisms and regulation
- Calcium signaling and nucleotide metabolism
- Traumatic Brain Injury and Neurovascular Disturbances
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
University of Pennsylvania
2016-2025
Penn Presbyterian Medical Center
2016-2025
University of Puerto Rico at Carolina
2023
American Academy of Ophthalmology
2023
Hospital of the University of Pennsylvania
2019
Ophthalmology Associates (United States)
2018
Georgetown University
2018
University of British Columbia
2018
University of Toronto
2018
University of Washington
2008-2018
Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form the disease, LCA2, caused by mutations in retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investigated safety subretinal delivery recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477 [ClinicalTrials.gov]). Three patients LCA2 had an acceptable local and systemic adverse-event profile after...
The safety and efficacy of gene therapy for inherited retinal diseases is being tested in humans affected with Leber's congenital amaurosis (LCA), an autosomal recessive blinding disease. Three independent studies have provided evidence that the subretinal administration adeno-associated viral (AAV) vectors encoding RPE65 patients LCA2 due to mutations gene, safe and, some cases, results efficacy. We evaluated long-term (global effects on retinal/visual function) resulting from...
Demonstration of safe and stable reversal blindness after a single unilateral subretinal injection recombinant adeno-associated virus (AAV) carrying the RPE65 gene (AAV2-hRPE65v2) prompted us to determine whether it was possible obtain additional benefit through second administration AAV vector contralateral eye. Readministration eye carried out in three adults with Leber congenital amaurosis due mutations 1.7 3.3 years they had received their initial AAV2-hRPE65v2. Results (through 6...
Monoclonal antibodies (MAbs) capable of recognizing developmental stage-specific neuronal epitopes are becoming increasingly available. Because most these MAbs raised in a single species (mouse), simultaneous immunofluorescent detection multiple has been difficult. We have taken advantage the high sensitivity tyramide signal amplification to develop protocol that permits two same species. One primary antibody was applied at concentration below limit fluorescently labeled secondary...
Background: Neuronal loss in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), correlates with permanent neurological dysfunction. Current MS therapies have limited the ability to prevent neuronal damage. Methods: We examined whether oral therapy SRT501, a pharmaceutical grade formulation of resveratrol, reduces during relapsing-remitting EAE. Resveratrol activates SIRT1, an NAD+-dependent deacetylase that promotes mitochondrial function. Results:...
Axonal damage and loss of neurons correlate with permanent vision neurologic disability in patients optic neuritis multiple sclerosis (MS). Current therapies involve immunomodulation, limited effects on neuronal damage. The authors examined potential neuroprotective by SRT647 SRT501, two structurally mechanistically distinct activators SIRT1, an enzyme involved cellular stress resistance survival.
Abstract Background Interleukin-17A (IL-17A) is the founding member of a novel family inflammatory cytokines that plays critical role in pathogenesis many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental encephalomyelitis (EAE). IL-17A signals through receptor, IL-17RA, which expressed peripheral tissues; however, expression IL-17RA central nervous system (CNS) CNS inflammation are not well understood. Methods EAE was induced C57Bl/6 mice by...
Resveratrol is a naturally occurring polyphenol that activates SIRT1, an NAD-dependent deacetylase. SRT501, pharmaceutical formulation of resveratrol with enhanced systemic absorption, prevents neuronal loss without suppressing inflammation in mice relapsing experimental autoimmune encephalomyelitis (EAE), model multiple sclerosis (MS). In contrast, has been reported to suppress chronic EAE, although neuroprotective effects were not evaluated. The current studies examine potential and...
Leber congenital amaurosis (LCA) is a rare degenerative eye disease, linked to mutations in at least 14 genes. A recent gene therapy trial patients with LCA2, who have RPE65, demonstrated that subretinal injection of an adeno-associated virus (AAV) carrying the normal cDNA (AAV2-hRPE65v2) could markedly improve vision. However, it remains unclear how visual cortex responds recovery retinal function after prolonged sensory deprivation. Here, 3 subjects, treated ages 8, 9, and 35 years,...
The study purpose was to examine vision-specific and overall health-related quality of life (QOL) at baseline in Idiopathic Intracranial Hypertension Treatment Trial patients who were newly diagnosed had mild visual loss. We also sought determine the associations between QOL scores symptoms, function, pain, headache-related disability, obesity.
The intracellular balance between pro- and antiapoptotic members of the Bcl-2 gene family is thought to regulate cell death. Targeted disruption bcl-x , a death repressing member, causes massive immature neurons in developing mouse CNS, whereas targeted bax proapoptotic blocks specific populations sympathetic motor neurons. In present study, mice deficient both Bcl-x L Bax ( −/− / ) are used examine relative significance potential interactions during early CNS development. demonstrate...
Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are neurodegenerative diseases with characteristic inflammatory demyelination in the central nervous system, including optic nerve. Neuronal axonal damage is considered to be main cause of long-term disability patients MS. loss, retinal ganglion cell (RGC) apoptosis eyes neuritis (ON), also occurs EAE. However, there significant variability clinical course level neuronal MS The current studies...
Activation of SIRT1, an NAD+-dependent deacetylase, prevents retinal ganglion cell (RGC) loss in optic neuritis, inflammatory demyelinating nerve disease. While SIRT1 deacetylates numerous protein targets, downstream mechanisms activation mediating this neuroprotective effect are unknown. increases mitochondrial function and reduces oxidative stress muscle other cells, occurs neuronal degeneration. We examined whether activators reduce promote cells. Oxidative stress, marked by reactive...
<h3>Objectives:</h3> Determine potential risk factors for progressive visual field loss in the Idiopathic Intracranial Hypertension Treatment Trial, a randomized placebo-controlled trial of acetazolamide patients with idiopathic intracranial hypertension and mild concurrently receiving low sodium, weight reduction diet. <h3>Methods:</h3> Logistic regression classification tree analyses were used to evaluate protocol-defined treatment failure (>2 dB perimetric mean deviation [PMD] change...
Activation of SIRT1 deacetylase prevents retinal ganglion cell (RGC) loss in experimental optic neuritis, an inflammatory neuropathy. While mechanisms this effect are not known, evidence suggests it involves reduction oxidative stress. We hypothesized that reduces RGC due to stress noninflammatory neuropathies, and examined effects following traumatic injury.Optic nerve crush injury was induced wild-type C57BL/6 mice, mice overexpressing SIRT1, with conditional deletion neurons. Wild-type...
Multiple sclerosis (MS) is characterized by central nervous system inflammation and demyelination, increasing evidence demonstrates significant neuronal damage also occurs associated with permanent functional impairment. Current MS therapies have limited ability to prevent damage, suggesting additional neuroprotective are needed. Compounds that activate the NAD+-dependent SIRT1 deacetylase loss in an autoimmune-mediated model, but mechanism of this effect unknown, it unclear whether...
Revised diagnostic criteria for idiopathic intracranial hypertension (IIH) were proposed in part to reduce misdiagnosis of without papilledema (WOP) by using 3 or 4 MRI features when a sixth nerve palsy is absent. This study was undertaken evaluate the sensitivity and specificity validate their utility diagnosing IIH patients with chronic headaches elevated opening pressure (CH + EOP), but WOP.Brain MRIs from 80 (WP), 33 CH EOP, 70 control infrequent episodic migraine assessed masked fashion...
The number of neurons in the mammalian brain is determined by a balance between cell proliferation and programmed death. Recent studies indicated that Bcl-X L prevents, whereas Caspase-3 mediates, death developing nervous system, but whether directly blocks apoptotic function vivo not known. To examine this question, we generated bcl-x / caspase-3 double mutants found deficiency abrogated increased apoptosis postmitotic hematopoietic embryonic lethality caused mutation. In contrast, ,...
Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are marked by inflammatory demyelinating lesions throughout the central nervous system, including optic nerve. Neuronal loss also occurs in MS EAE lesions, but it is not known whether neuronal secondary to inflammation, or as a primary process. In current study, relationship of inflammation retinal ganglion cell (RGC) during acute neuritis examined. RGCs were labelled with Flourogold, was induced...
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Recent studies have demonstrated that significant axonal injury also occurs in MS patients and correlates with neurological dysfunction, but it not known whether this neuronal damage a primary process, or only secondary to demyelination. In current studies, neurotropic strains mouse hepatitis virus (MHV) induce meningitis, encephalitis, demyelination CNS, animal model MS, were used evaluate mechanisms injury. The...