Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Tschernutter, M; Schlichtenbrede, FC; Howe, S; Balaggan, KS; Munro, PM; Bainbridge, JW; Thrasher, AJ; Smith, AJ; Ali, RR.
Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy.
Gene Ther. 2005; 12(8): 694-701.
Doi: 10.1038/sj.gt.3302460
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- Führende Autor*innen der Med Uni Graz
- Tschernutter Marion
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- Abstract:
- The Royal College of Surgeons (RCS) rat is a well-characterized model of autosomal recessive retinitis pigmentosa (RP) due to a defect in the retinal pigment epithelium (RPE). It is homozygous for a null mutation in the gene encoding , a receptor tyrosine kinase found in RPE cells, that is required for phagocytosis of shed photoreceptor outer segments. The absence of Mertk results in accumulation of outer segment debris. This subsequently leads to progressive loss of photoreceptor cells. In order to evaluate the efficacy of lentiviral-mediated gene replacement therapy in the RCS rat, we produced recombinant VSV-G pseudotyped HIV-1-based lentiviruses containing a murine Mertk cDNA driven by a spleen focus forming virus (SFFV) promoter. The vector was subretinally injected into the right eye of 10-day-old RCS rats; the left eye was left untreated as an internal control. Here, we present a detailed assessment of the duration and extent of the morphological rescue and the resulting functional benefits. We examined animals at various time points over a period of 7 months by light and electron microscopy, and electroretinography. We observed correction of the phagocytic defect, slowing of photoreceptor cell loss and preservation of retinal function for up to 7 months. This study demonstrates the potential of gene therapy approaches for the treatment of retinal degenerations caused by defects specific to the RPE and supports the use of lentiviral vectors for the treatment of such disorders.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Electroretinography -
- Genetic Therapy - methods
- Genetic Vectors - administration & dosage
- HIV-1 - genetics
- Humans -
- Injections -
- Microscopy, Electron -
- Models, Animal -
- Photoreceptor Cells - pathology
- Pigment Epithelium of Eye - metabolism Pigment Epithelium of Eye - physiopathology Pigment Epithelium of Eye - ultrastructure
- Promoter Regions, Genetic -
- Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism
- Rats -
- Rats, Mutant Strains -
- Receptor Protein-Tyrosine Kinases - genetics Receptor Protein-Tyrosine Kinases - metabolism
- Recombinant Fusion Proteins - administration & dosage Recombinant Fusion Proteins - genetics
- Retinitis Pigmentosa - metabolism Retinitis Pigmentosa - pathology Retinitis Pigmentosa - therapy
- Spleen Focus-Forming Viruses - genetics
- Time Factors -
- Find related publications in this database (Keywords)
- retinitis pigmentosa
- lentivirus
- RCS rat
- MERTK
- retinal pigment epithelium