March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Additional Neuroprotective Effects Of Proinsulin On Vision And Retinal Structure In The Rd10 Mouse Model Of Retinitis Pigmentosa
Author Affiliations & Notes
  • Enrique J. de la Rosa
    Cell & Molecular Medicine, Centro de Investigaciones Biologicas, Madrid, Spain
  • Nuria Forns
    Physiology, University of Alcala, Alcala de Henares, Spain
  • Miguel Marchena
    Physiology, University of Alcala, Alcala de Henares, Spain
  • Alberto Hernandez-Pinto
    Cell & Molecular Medicine, Centro de Investigaciones Biologicas, Madrid, Spain
  • Ryan Steel
    Cell & Molecular Medicine, Centro de Investigaciones Biologicas, Madrid, Spain
  • Carolina Isiegas
    ProRetina Therapeutics SL, Madrid, Spain
  • Eduard Ayuso
    CBATEG, Universitat Autònoma de Barcelona, Bellaterra, Spain
  • Flora de Pablo
    Cell & Molecular Medicine, Centro de Investigaciones Biologicas, Madrid, Spain
  • Fátima Bosch
    CBATEG, Universitat Autònoma de Barcelona, Bellaterra, Spain
  • Pedro de la Villa
    Physiology, University of Alcala, Alcala de Henares, Spain
  • Footnotes
    Commercial Relationships  Enrique J. de la Rosa, proinsulin (P), ProRetina Therapeutics (F, I); Nuria Forns, None; Miguel Marchena, None; Alberto Hernandez-Pinto, ProRetina Therapeutics (F); Ryan Steel, None; Carolina Isiegas, ProRetina Therapeutics (I, E); Eduard Ayuso, ProRetina Therapeutics (F, I); Flora de Pablo, proinsulin (P), ProRetina Therapeutics (I); Fátima Bosch, proinsulin (P), ProRetina Therapeutics (F, I); Pedro de la Villa, proinsulin (P), ProRetina Therapeutics (I)
  • Footnotes
    Support  SAF2010-21879 (Spain)
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6447. doi:https://doi.org/
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      Enrique J. de la Rosa, Nuria Forns, Miguel Marchena, Alberto Hernandez-Pinto, Ryan Steel, Carolina Isiegas, Eduard Ayuso, Flora de Pablo, Fátima Bosch, Pedro de la Villa; Additional Neuroprotective Effects Of Proinsulin On Vision And Retinal Structure In The Rd10 Mouse Model Of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6447. doi: https://doi.org/.

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

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Abstract

Purpose: : Retinitis pigmentosa (RP) is a heterogeneous group of inherited conditions that lead to blindness. Apoptosis of photoreceptors and retinal disorganization are common features in animal models of the disease. We have previously shown that proinsulin delays vision loss, as determined by electroretinography (ERG), and retinal degeneration, as determined by photoreceptor counting, in the rd10 and P23H models of RP. To identify additional potential benefits of a proinsulin-based treatment, we further analyzed other parameters such as the optomotor behavior and the synaptic integrity, as well as different delivery methods, in the rd10 mouse

Methods: : Untreated rd10 mice or rd10 mice expressing human proinsulin (hPi) in the skeletal muscle, either by transgenesis or after intramuscular injection of adeno-associated viral vector encoding hPi (AAV-hPi) at postnatal day 10 (P10), were studied. Visual function was evaluated by ERG and optomotor test. Immunohistochemistry was employed to assess retinal structure and synaptic preservation.

Results: : Both transgenic and AAV-mediated expression of hPi in rd10 mice led to prolonged vision, as determined by ERG. Interestingly, visual function, as determined by the optomotor test, extends beyond the complete loss of ERG response. AAV-hPi treatment prolongs ERG response longer than transgenic expression. On the contrary, photoreceptor cell loss is less attenuated by AAV-hPi treatment. Functional preservation in this case may reside in the synaptic maintenance, as determined by colocalization of synaptic markers such as Basoon and mGluR6 or PKC.

Conclusions: : These results confirm the neuroprotective effects of proinsulin and support that proinsulin may play an active therapeutic role by preserving synaptic function during the neurodegenerative process.

Keywords: neuroprotection • retinitis • synapse 
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