losartan-potassium and Retinitis-Pigmentosa

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.. 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.. 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.. 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.

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

Topics: Adult; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Recombinant Proteins; Retinal Detachment; Retinal Neovascularization; Retinitis Pigmentosa