Virus-mediated EpoR76E Therapy Slows Optic Nerve Axonopathy in Experimental Glaucoma.
Glaucoma, a common cause of blindness, is currently treated by intraocular pressure (IOP)-lowering interventions. However, this approach is insufficient to completely prevent vision loss. Here, we evaluate an IOP-independent gene therapy strategy using a modified erythropoietin, EPO-R76E, which has reduced erythropoietic function. We used two models of glaucoma, the murine microbead occlusion model and the DBA/2J mouse. Systemic recombinant adeno-associated virus-mediated gene delivery of EpoR76E (rAAV.EpoR76E) was performed concurrent with elevation of IOP. Axon structure and active anterograde transport were preserved in both models. Vision, as determined by the flash visual evoked potential, was preserved in the DBA/2J. These results show that systemic EpoR76E gene therapy protects retinal ganglion cells from glaucomatous degeneration in two different models. This suggests that EPO targets a component of the neurodegenerative pathway that is common to both models. The efficacy of rAAV.EpoR76E delivered at onset of IOP elevation supports clinical relevance of this treatment.
Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Wesley S
WS
Bond
Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Jessica
J
Hines-Beard
Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
YPaul L
YL
GoldenMerry
Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Mara
M
Davis
Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Alma
A
Farooque
Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Rebecca M
RM
Sappington
Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
David J
DJ
Calkins
Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA. Electronic address: tonia.rex@vanderbilt.edu.
Tonia S
TS
Rex
D000818:Animals; D001369:Axons / Q000473:pathology*; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D005901:Glaucoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007429:Intraocular Pressure; D051379:Mice; D009154:Mutation; D009900:Optic Nerve / Q000473:pathology*
C554270:EPO protein, human; D004921:Erythropoietin