Long-term photoreceptor rescue in two rodent models of retinitis pigmentosa by adeno-associated virus delivery of Stanniocalcin-1
| Autor: | Sanford L. Boye, Gavin W. Roddy, Matthew M. LaVail, Robert H. Rosa, Michael T. Matthes, Michael P. Fautsch, Douglas Yasumura, Marcel V. Alavi, William W. Hauswirth |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Retinal degeneration Stanniocalcin-1 Neurodegenerative Medical Biochemistry and Metabolomics Eye Ophthalmology & Optometry Transgenic chemistry.chemical_compound 0302 clinical medicine 2.1 Biological and endogenous factors Aetiology Gene therapy of the human retina medicine.diagnostic_test Gene Therapy Dependovirus Sensory Systems Neuroprotection medicine.anatomical_structure Neuroprotective Agents Retinal ganglion cell Rats Transgenic Erg Retinitis Pigmentosa Photoreceptor Cells Vertebrate Biotechnology medicine.medical_specialty Rhodopsin Biology Article Andrology 03 medical and health sciences Cellular and Molecular Neuroscience S334ter Opthalmology and Optometry Ophthalmology Retinitis pigmentosa medicine Electroretinography P23H Genetics Animals Photoreceptor Cells Eye Disease and Disorders of Vision Glycoproteins Animal Vertebrate Neurosciences Retinal Macular degeneration medicine.disease Rats Disease Models Animal 030104 developmental biology chemistry Disease Models 030221 ophthalmology & optometry sense organs |
| Popis: | Retinal degenerations, including age-related macular degeneration and the retinitis pigmentosa family of diseases, are among the leading causes of legal blindness in the United States. We previously found that Stanniocalcin-1 (STC-1) reduced photoreceptor loss in the S334ter-3 and Royal College of Surgeons rat models of retinal degeneration. The results were attributed in part to a reduction in oxidative stress. Herein, we tested the hypothesis that long-term delivery of STC-1 would provide therapeutic rescue in more chronic models of retinal degeneration. To achieve sustained delivery, we produced an adeno-associated virus (AAV) construct to express STC-1 (AAV-STC-1) under the control of a retinal ganglion cell targeting promoter human synapsin 1 (hSYN1). AAV-STC-1 was injected intravitreally into the P23H-1 and S334ter-4 rhodopsin transgenic rats at postnatal day 10. Tissues were collected at postnatal day 120 for confirmation of STC-1 overexpression and histologic and molecular analysis. Electroretinography (ERG) was performed in a cohort of animals at that time. Overexpression of STC-1 resulted in a significant preservation of photoreceptors as assessed by outer nuclear thickness in the P23H-1 (P |
| Databáze: | OpenAIRE |
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