Erythropoietin Slows Photoreceptor Cell Death in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa.

Rex TS, Kasmala L, Bond WS, de Lucas Cerrillo AM, Wynn K, Lewin AS
PLoS One. 2016 11 (6): e0157411

PMID: 27299810 · PMCID: PMC4907422 · DOI:10.1371/journal.pone.0157411

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.

MeSH Terms (14)

Animals Cell Death Dependovirus Disease Models, Animal Erythropoietin Genetic Therapy Gene Transfer Techniques Humans Mice Opsins Point Mutation Retinal Cone Photoreceptor Cells Retinitis Pigmentosa Vision, Ocular

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