April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Proinsulin Delays Retinal Degeneration and Vision Loss in the P23H Rat
Author Affiliations & Notes
  • Carolina Isiegas
    Centro de Investigaciones Biologicas and CEIN, ProRetina Therapeutics SL, Madrid and Noain, Spain
  • Pedro Lax
    Universidad de Alicante, Alicante, Spain
  • Laura Fernández-Sánchez
    Universidad de Alicante, Alicante, Spain
  • María Jesús Cano
    Centro de Investigaciones Biologicas and CEIN, ProRetina Therapeutics SL, Madrid and Noain, Spain
  • José María Ruiz
    Centro de Investigaciones Biologicas and CEIN, ProRetina Therapeutics SL, Madrid and Noain, Spain
  • Eduard Ayuso
    Universitat Autonoma de Barcelona, Barcelona, Spain
  • Fátima Bosch
    Universitat Autonoma de Barcelona, Barcelona, Spain
  • Flora de Pablo
    Dept. of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain
  • Enrique J. de la Rosa
    Dept. of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain
  • Nicolas Cuenca
    Universidad de Alicante, Alicante, Spain
  • Footnotes
    Commercial Relationships  Carolina Isiegas, ProRetina Theapeutics SL (E), ProRetina Therapeutics SL (I); Pedro Lax, ProRetina Therapeutics S.L. (F); Laura Fernández-Sánchez, ProRetina Therapeutics S.L. (F); María Jesús Cano, ProRetina Therapeutics S.L. (E); José María Ruiz, ProRetina Therapeutics S.L. (E); Eduard Ayuso, ProRetina Therapeutics S.L. (I), ProRetina Therapeutics, S.L. (F); Fátima Bosch, ProRetina Therapeutics S.L. (F, I, P); Flora de Pablo, ProRetina Therapeutics S.L. (I, P), ProRetina Therapeutics, S.L. (F); Enrique J. de la Rosa, ProRetina Therapeutics S.L. (I, P), ProRetina Therapeutics, S.L. (F); Nicolas Cuenca, ProRetina Therapeutics S.L. (F)
  • Footnotes
    Support  TRACE (PET08-0282) to EJ de la Rosa. Loans from CDTI, Ministerio de Ciencia e Innovacion, and Empresa Nacional de Innovacion, S.A. to ProRetina Therapeutics S.L.
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4357. doi:https://doi.org/
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      Carolina Isiegas, Pedro Lax, Laura Fernández-Sánchez, María Jesús Cano, José María Ruiz, Eduard Ayuso, Fátima Bosch, Flora de Pablo, Enrique J. de la Rosa, Nicolas Cuenca; Proinsulin Delays Retinal Degeneration and Vision Loss in the P23H Rat. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4357. 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 retinal degenerations that lead to blindness and for which there is no effective therapy. Photoreceptor cell death is a major hallmark in RP patients and in animal models of the disease. Previous studies have shown that transgenic and AAV-mediated expression of the antiapoptotic molecule proinsulin delays retinal degeneration in the rd10 mouse model of RP. The objective of this study is to assess the therapeutic potential of proinsulin in the P23H rat model of RP.

 
Methods:
 

An adeno-associated viral vector serotype 1 (AAV2/1) expressing human proinsulin (hPi) under the control of the cytomegalovirus (CMV) promoter has been generated. P23H homozygous (line 3) rats have received an intramuscular injection of AAV2/1-hPi (hPi+) or AAV2/1-null (hPi-) vector at P20. In these rats, levels of hPi in serum have been determined by ELISA, and visual function has been evaluated by electroretinographic (ERG) recording at P30, P60, P90 and P120. Preservation of retinal structure has been assessed by immunohistochemistry at P120.

 
Results:
 

Human proinsulin was detected in serum from rats injected with hPi+ at all times tested, with average hPi levels ranging from 1,1 nM (P30) to 1,4 nM (P120). ERG recordings showed an amelioration of vision loss in hPi+ animals. Thus, the scotopic b-waves were significantly higher in hPi+ animals than in control hPi- rats at P90 and P120 (p<0.05 and p<0.01, respectively; ANOVA). This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture.

 
Conclusions:
 

Our data demonstrate that hPi expression attenuates the retinal degeneration and the loss of retinal function in the P23H rat. Notably, these results constitute additional proof of concept of what we have previously observed in a different animal model of RP. All together, these data lay solid grounds to develop a proinsulin-based therapy to treat retinitis pigmentosa.

 
Keywords: neuroprotection • retina • adenovirus 
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