Erythropoietin Slows Photoreceptor Cell Death in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa.
OBJECTIVE
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.
Vanderbilt Eye Institute, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, United States of America.
Tonia S
http://orcid.org/0000-0002-2566-8723
TS
Rex
Vanderbilt Eye Institute, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, United States of America.
Lorraine
L
Kasmala
Vanderbilt Eye Institute, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, United States of America.
Wesley S
WS
Bond
Vanderbilt Eye Institute, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, United States of America.
Ana M
AM
de Lucas Cerrillo
Vanderbilt Eye Institute, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, United States of America.
Kristi
K
Wynn
Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, FL 32608, United States of America.
Alfred S
AS
Lewin
D000818:Animals; D016923:Cell Death; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000235:genetics* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D055355:Opsins / Q000032:analysis; D017354:Point Mutation; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D014785:Vision, Ocular
D055355:Opsins; D004921:Erythropoietin