Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme.

Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme. Abstract Text:

M Gorbatyuk,V Justilien,J Liu,W W Hauswirth,A S Lewin,

To develop an allele independent ribozyme for the treatment of autosomal dominant retinitis pigmentosa (ADRP) associated with mutations in the rhodopsin (RHO) gene, a ribozyme targeting dog, mouse, human but not rat rhodopsin (RHO) mRNA was designed and tested in vitro. Activity of this ribozyme was tested in tissue culture by co-transfection of HEK 293 cells with plasmids expressing opsin mRNA and ribozyme, followed by quantitative RT-PCR to evaluate the level of RHO mRNA. For experiments in vivo, Rz525 driven by the mouse opsin proximal promoter was inserted in plasmids with AAV 2 terminal repeats (TR) and packaged in AAV serotype 5 capsids. AAV-Rz525 was injected subretinally into the right eyes of P23H rat pups. Left eyes were injected with virus expressing GFP from the identical promoter. Animals were analyzed at 4, 8 and 12 weeks post-injection by full field scotopic electroretinography (ERG). After 12 weeks, animals were sacrificed and retinas were dissected, fixed and sectioned. Rz525 had high catalytic activity in vitro and led to a 50% reduction of RHO mRNA in cells. AAV-Rz525 injection into P23H transgenic rats led to significant preservation (about 50%) of scotopic ERG a- and b-wave amplitudes. Histological analysis showed an increased number of ONL nuclei in the central and superior retina of treated eyes relative to control eyes. RT-PCR analysis revealed 46% reduction of transgenic (mouse) RHO mRNA in right eyes relative to left eyes and no change in rat RHO mRNA. AAV5 delivery of Rz525 resulted in a partial rescue of the light response and structural preservation of photoreceptors in transgenic rats. This ribozyme may be a useful component of an RNA replacement gene therapy for ADRP.

Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme. Publishing Authors By Initials

M Gorbatyuk,V Justilien,J Liu,WW Hauswirth,AS Lewin,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

PUBMED ID PMID:

MEDLINE DATE:

Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Experimental eye research

VOLUME: 84

Page Numbers: 44-52

Journal Abbreviation: Exp. Eye Res.

ISSN: 0014-4835

DAY: 1

MONTH: 11

YEAR: 2006

Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370707

Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: genetics

Chemical & Substance for Abstract: Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme. Information

Substance Name: Rhodopsin

Registry Number: 9009-81-8

Grant and Affiliation Information for Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme.

AFFILIATION: Department of Molecular Genetics and Microbiology, University of Florida, Box 100266, Gainesville, FL 32610, USA. mari543@ufl.edu

Country: England

AGENCY: United States NEI

GRANT: R01EY011596

ACRONYM: EY

MEDLINETA: Exp Eye Res

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme Related Publications

• A hollow delayed surgical obturator for a bilateral subtotal maxillectomy patient: A clinical report.
• A preliminary case-mix classification system for Home and Community Care Clients in Western Australia.
• Acute subdural and extradural haematoma in closed head injuries.
• Development and validation of a very brief questionnaire measure of physical activity in adults with coronary heart disease.
• Digital mammography: comparative performance of color LCD and monochrome CRT displays.
• Discovery and characterization of 91 novel transcripts expressed in cattle placenta.
• Dysphagia after chemoradiation: prevention and treatment.
• Failure to validate the Health Survey for England physical activity module in a cardiac population.
• Genomic organization and evolution of the ULBP genes in cattle.
• Germination of zygospores in chlamydomonas.
• Human thymic dendritic cells: Regulators of T cell development in health and HIV-1 infection.
• Infections of the bones and joints.
• Living with heart failure; patient and carer perspectives.
• Nutrition-induced ketosis alters metabolic and signaling gene networks in liver of periparturient dairy cows.
• Ontogeny of mRNA expression and activity of long-chain acyl-CoA synthetase (ACSL) isoforms in Mus musculus heart.
• Painful conditions of the foot and ankle.
• Preliminary evidence for sleep complaints among children referred for anxiety.
• Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme.
• SOD2 knockdown mouse model of early AMD.
• Sleep characteristics of youth with functional abdominal pain and a healthy comparison group.
• Stomatin and sensory neuron mechanotransduction.
• Suppression of mouse rhodopsin expression in vivo by AAV mediated siRNA delivery.
• The knee joint.
• The nature of reality, the meaning of nothing, with an addendum on concentration.
• The phenotype of hepatitis B virus-specific T cells differ in the liver and blood in chronic hepatitis B virus infection.
• [Diagnosis of tubal pregnancy by the graduated frog test.]
• [Histochemical studies on the placenta in extrauterine pregnancy.]
• [Histochemical study of the mucous membrane of extrauterine pregnancies. II.]
• [Hyperemia reaction in rat ovary as rapid pregnancy test.]
• [Ovulation as a physiological process.]