Erythropoietin Slows Photoreceptor Cell Death in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa
| Autor: | Kristi Wynn, Wesley S. Bond, Tonia S. Rex, Lorraine Kasmala, Alfred S. Lewin, Ana M. de Lucas Cerrillo |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Retinal degeneration Photoreceptors Sensory Receptors genetic structures Vision lcsh:Medicine Social Sciences Photoreceptor cell Mice 0302 clinical medicine Animal Cells Medicine and Health Sciences Psychology lcsh:Science Neurons Multidisciplinary Gene therapy of the human retina biology Cell Death Retinal Degeneration Gene Transfer Techniques Anatomy Animal Models Dependovirus 3. Good health medicine.anatomical_structure Rhodopsin Cell Processes Retinal Cone Photoreceptor Cells Retinal Disorders Sensory Perception Cellular Types Retinitis Pigmentosa Research Article Signal Transduction Ocular Anatomy Mouse Models Gene delivery Research and Analysis Methods Retina 03 medical and health sciences Gene Delivery Model Organisms Ocular System Retinitis pigmentosa medicine Gene Expression and Vector Techniques Animals Humans Point Mutation Outer nuclear layer Molecular Biology Techniques Molecular Biology Erythropoietin Vision Ocular Molecular Biology Assays and Analysis Techniques Opsins lcsh:R Retinitis Biology and Life Sciences Afferent Neurons Cell Biology Genetic Therapy medicine.disease Molecular biology Ophthalmology Disease Models Animal 030104 developmental biology Cellular Neuroscience 030221 ophthalmology & optometry biology.protein lcsh:Q sense organs Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 6, p e0157411 (2016) |
| ISSN: | 1932-6203 |
| Popis: | Purpose To test the efficacy of systemic gene delivery of a mutant form of erythropoietin (EPO-R76E) that has attenuated erythropoietic activity, in a mouse model of autosomal dominant retinitis pigmentosa. Methods Ten-day old mice carrying one copy of human rhodopsin with the P23H mutation and both copies of wild-type mouse rhodopsin (hP23H RHO+/-,mRHO+/+) were injected into the quadriceps with recombinant adeno-associated virus (rAAV) carrying either enhanced green fluorescent protein (eGFP) or EpoR76E. Visual function (electroretinogram) and retina structure (optical coherence tomography, histology, and immunohistochemistry) were assessed at 7 and 12 months of age. Results The outer nuclear layer thickness decreased over time at a slower rate in rAAV.EpoR76E treated as compared to the rAAV.eGFP injected mice. There was a statistically significant preservation of the electroretinogram at 7, but not 12 months of age. Conclusions Systemic EPO-R76E slows death of the photoreceptors and vision loss in hP23H RHO+/-,mRHO+/+ mice. Treatment with EPO-R76E may widen the therapeutic window for retinal degeneration patients by increasing the number of viable cells. Future studies might investigate if co-treatment with EPO-R76E and gene replacement therapy is more effective than gene replacement therapy alone. |
| Databáze: | OpenAIRE |
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