June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Functional Biomarkers For Successful Molecular Therapy Of The Outer Retina In Retinal Degenerations
Author Affiliations & Notes
  • Vithiyanjali Sothilingam
    Division of Ocular Degeneration, Ctr for Ophthal Inst for Ophthalmic Rsch, Tuebingen, Germany
  • Marina Garcia Garrido
    Division of Ocular Degeneration, Ctr for Ophthal Inst for Ophthalmic Rsch, Tuebingen, Germany
  • Christina Seide
    Division of Ocular Degeneration, Ctr for Ophthal Inst for Ophthalmic Rsch, Tuebingen, Germany
  • Susanne Koch
    Department of Pharmacy-Centre for Drug Research, Center for Integrated Protein Science Munich (CIPSM), Munich, Germany
  • Stylianos Michalakis
    Department of Pharmacy-Centre for Drug Research, Center for Integrated Protein Science Munich (CIPSM), Munich, Germany
  • Martin Biel
    Department of Pharmacy-Centre for Drug Research, Center for Integrated Protein Science Munich (CIPSM), Munich, Germany
  • Naoyuki Tanimoto
    Division of Ocular Degeneration, Ctr for Ophthal Inst for Ophthalmic Rsch, Tuebingen, Germany
  • Mathias Seeliger
    Division of Ocular Degeneration, Ctr for Ophthal Inst for Ophthalmic Rsch, Tuebingen, Germany
  • Footnotes
    Commercial Relationships Vithiyanjali Sothilingam, None; Marina Garcia Garrido, None; Christina Seide, None; Susanne Koch, None; Stylianos Michalakis, None; Martin Biel, None; Naoyuki Tanimoto, None; Mathias Seeliger, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2742. doi:
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      Vithiyanjali Sothilingam, Marina Garcia Garrido, Christina Seide, Susanne Koch, Stylianos Michalakis, Martin Biel, Naoyuki Tanimoto, Mathias Seeliger; Functional Biomarkers For Successful Molecular Therapy Of The Outer Retina In Retinal Degenerations. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2742.

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

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Abstract 
 
Purpose
 

Retinal degenerations are severe and frequently blinding human diseases. Several current therapeutic approaches have demonstrated long-lasting amelioration in respective disease models and show promise for a successful translation to human patients. Here, we focus on electroretinographic (ERG) features in the experimental data in order to identify informative biomarkers for upcoming clinical trials.

 
Methods
 

Core of this work is the electrophysiologic evaluation of treated mouse models representing achromatopsia (Cnga3-/-) or retinitis pigmentosa (Cngb1-/-). Mice of these lines received adeno-associated virus (AAV)-mediated gene replacement therapy designed to express mouse CNGA3 or CNGB1 under control of respective photoreceptor-specific promoters (mouse S opsin or rhodopsin). Treatment success was monitored with different single flash and flicker protocols of in vivo electrophysiology. The findings were compared to immunohistochemistry, in vivo imaging, and behavioral assays.

 
Results
 

In both disease models, the therapeutic effects were well detectable with several of the explorative ERG protocols used in this study. However, the signal-to-noise ratio varied between the particular tests, depending on the nature of the underlying disease (rod- or cone-specific origin). On this basis, options for biomarkers were developed for potential use in human trials.

 
Conclusions
 

The ERG is a very effective method to assess outer retinal functionality. We show here that specific ERG protocols are well suited to follow therapeutic effects in retinal degenerations. Such tests may thus serve as functional biomarkers for molecular therapy in upcoming clinical trials.

 
Keywords: 508 electrophysiology: non-clinical • 538 gene transfer/gene therapy • 696 retinal degenerations: hereditary  
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