Open AccessErythropoietin Slows Photoreceptor Cell Death in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa
Author(s) -
Tonia S. Rex,
L Kasmala,
Wesley S. Bond,
Ana M. de Lucas Cerrillo,
Kristi Wynn,
Alfred S. Lewin
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0157411
Subject(s) - retinitis pigmentosa , erythropoietin , retinal degeneration , photoreceptor cell , rhodopsin , genetic enhancement , outer nuclear layer , electroretinography , retina , gene therapy of the human retina , retinal , biology , pathology , medicine , microbiology and biotechnology , ophthalmology , endocrinology , gene , genetics , neuroscience
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 +/- ,m RHO +/+ ) 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 +/- ,m RHO +/+ 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.