May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Proinsulin Attenuates Vision Loss and Delays Photoreceptor Apoptosis in a Mouse Model of Retinitis Pigmentosa
Author Affiliations & Notes
  • E. J. de la Rosa
    Cellular and Molecular Physiopathology, Centro de Investigaciones Biologicas, Madrid, Spain
  • S. Corrochano
    Cellular and Molecular Physiopathology, Centro de Investigaciones Biologicas, Madrid, Spain
  • R. Barhoum
    Physiology, Universidad de Alcalá, Alcalá de Henares, Spain
  • P. Boya
    Cellular and Molecular Physiopathology, Centro de Investigaciones Biologicas, Madrid, Spain
  • A. I. Arroba
    Cellular and Molecular Physiopathology, Centro de Investigaciones Biologicas, Madrid, Spain
  • N. Rodríguez-Muela
    Cellular and Molecular Physiopathology, Centro de Investigaciones Biologicas, Madrid, Spain
  • V. Gómez-Vicente
    Cellular and Molecular Physiopathology, Centro de Investigaciones Biologicas, Madrid, Spain
  • F. Bosch
    Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain
  • F. de Pablo
    Cellular and Molecular Physiopathology, Centro de Investigaciones Biologicas, Madrid, Spain
  • P. de la Villa
    Physiology, Universidad de Alcalá, Alcalá de Henares, Spain
  • Footnotes
    Commercial Relationships  E.J. de la Rosa, CSIC, P; S. Corrochano, CSIC, P; R. Barhoum, UAH, P; P. Boya, CSIC, P; A.I. Arroba, None; N. Rodríguez-Muela, None; V. Gómez-Vicente, None; F. Bosch, UAB, P; F. de Pablo, CSIC, P; P. de la Villa, UAH, P.
  • Footnotes
    Support  Spanish Grants SAF2001-1038 and SAF2004-05870 to EJdlR and PdlV; BFU2004-02352 to FdP; SAF2005-01262 to FB; RETIC RD-06 to FdP and FB;
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5842. doi:https://doi.org/
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      E. J. de la Rosa, S. Corrochano, R. Barhoum, P. Boya, A. I. Arroba, N. Rodríguez-Muela, V. Gómez-Vicente, F. Bosch, F. de Pablo, P. de la Villa; Proinsulin Attenuates Vision Loss and Delays Photoreceptor Apoptosis in a Mouse Model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5842. doi: https://doi.org/.

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Abstract

Purpose: : Retinitis pigmentosa is a heterogeneous group of inherited conditions that lead to blindness and for which there is no effective therapy. Apoptosis of photoreceptors is a common feature in animal models of the disease. Thus, we have studied the therapeutic potential of proinsulin, an antiapoptotic molecule that is active during retinal development.

Methods: : Transgenic mice expressing human proinsulin (hPi) in the skeletal muscle were generated in a mixed C57BL/6:SJL background and back-crossed to a C57BL/6 background. Two independent lineages of hPi/rd10 mice (L1 and L2) were established, in which hPi production in muscle was constitutive and not regulated by glucose levels. hPi levels in serum, muscle and retina were determined with a commercial ELISA kit, visual function was evaluated by electroretinogram recording and programmed cell death was assessed by TUNEL. Immunohistochemistry was used to evaluate oxidative damage and retinal structure preservation.

Results: : Transgenic expression of hPi in the retinal degeneration mouse model rd10 led to prolonged vision, as determined by electroretinogram recording, in a manner that was related to the level of transgene expression. This attenuation of visual deterioration was correlated with a delay in photoreceptor apoptosis, as well as with the preservation of retinal cytoarchitecture, particularly that of the cones.

Conclusions: : Our results provide a new basis for possible therapies to counteract retinitis pigmentosa, as well as a new tool to dissect out the mechanisms involved in the progress of retinal neurodegeneration.

Keywords: neuroprotection • cell survival • oxidation/oxidative or free radical damage 
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