June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Photoreceptor Protection in P23H RHO Transgenic Mice by Systemic Delivery of rAAV.EpoR76E
Author Affiliations & Notes
  • Ana de Lucas-Cerrillo
    Ophthalmology and Visual Sciences, Vanderbilt.University, Nashville, TN
    Ophthalmology, UTHSC, Memphis, TN
  • Lauren D'Surney
    Ophthalmology, UTHSC, Memphis, TN
  • Tonia Rex
    Ophthalmology and Visual Sciences, Vanderbilt.University, Nashville, TN
    Ophthalmology, UTHSC, Memphis, TN
  • Footnotes
    Commercial Relationships Ana de Lucas-Cerrillo, None; Lauren D'Surney, None; Tonia Rex, PCT/US2012/021247 (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 3258. doi:
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      Ana de Lucas-Cerrillo, Lauren D'Surney, Tonia Rex; Photoreceptor Protection in P23H RHO Transgenic Mice by Systemic Delivery of rAAV.EpoR76E. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3258.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To test the efficacy of erythropoietin R76E (EpoR76E) as a neuroprotective agent in the P23H mouse model of autosomal dominant retinitis pigmentosa.

Methods: One month old heterozygous P23H mice were injected in the quadriceps with1x109 gc of recombinant adeno-associated virus carrying enhanced green fluorescent protein (rAAV2/8. CMV.eGFP), as a negative control, or erythropoietin R76E (rAAV2/8. CMV.EpoR76E). At 7 months of age, retinal structure was assessed by optical coherence tomography (OCT) and histology to measure outer nuclear layer thickness. Hematocrit and serum EPO levels were measured. Using OCT, outer nuclear layer thickness was quantified at 30 μm and 60 μm from the optic nerve. Eyes were preserved in 4% paraformaldehyde, resin embedded and sectioned. Outer nuclear layer thickness was quantified every 500 microns from the optic nerve head in both directions using a Nikon Eclipse microscope and NIS-Elements software. Hematocrit was measured by capillary centrifugation of tail vein blood. Serum EPO levels were measured using the Quantikine human ELISA kit (R&D System) according to manufacturer’s instruction.

Results: OCT data showed preserved thickness of the ONL in mice injected with rAAV2/8.CMV.EpoR76E (60 μm ±0.01) compared to mice injected with rAAV2/8.CMV.eGFP (40 μm ±0.01), this difference was statistically significant (p<0.05). This result was confirmed histologically. Hematocrit levels were slightly, but not statistically significantly, higher in the mice treated with EPO.

Conclusions: Our results indicate that a single intramuscular injection of 1x109 gc rAAV2/8.CMV.EpoR76E protects photoreceptors against degeneration in P23H mice without a significant increase of hematocrit levels. Treatment with EPO in inherited retinal degenerations may preserve photoreceptors until gene-specific therapy is developed and available.

Keywords: 615 neuroprotection • 538 gene transfer/gene therapy • 696 retinal degenerations: hereditary  
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