April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Functional and Structural Retinal Modifications in the Igf1-/- Null Mouse
Author Affiliations & Notes
  • P. de la Villa
    Physiology, University of Alcala, Alcala de Henares, Spain
  • L. Rodriguez de la Rosa
    Instituto de Investigaciones Biomedicas, CSIC, Madrid, Spain
  • L. Fernandez Sanchez
    Fisiologia Genetica y Microbiologia, Universidad de Alicante, Alicante, Spain
  • S. Murillo Cuesta
    Instituto de Investigaciones Biomedicas, CSIC, Madrid, Spain
  • I. Varela-Nieto
    Instituto de Investigaciones Biomedicas, CSIC, Madrid, Spain
  • N. Cuenca
    Fisiologia Genetica y Microbiologia, Universidad de Alicante, Alicante, Spain
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2488. doi:
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      P. de la Villa, L. Rodriguez de la Rosa, L. Fernandez Sanchez, S. Murillo Cuesta, I. Varela-Nieto, N. Cuenca; Functional and Structural Retinal Modifications in the Igf1-/- Null Mouse. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2488.

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

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Abstract

Purpose: : It has been reported that mutations in the gene encoding human insulin-like growth factor-I (IGF-I) cause syndromic sensory dysfunction. To study the precise role of IGF-I in retinal physiology and to hypothesize the possible morphological and electrophysiological changes that may occur in the retina, we have focused on a mouse model of IGF-I deficiency (Igf1-/- homozygous null mice) in comparison with Igf1-/+ heterozygous and wild type (wt) animals.

Methods: : We have analyzed the retinal function by means of electroretinographic (ERG) responses and the retinal morphology by the use of immunocytochemical labeling on retinal preparations.

Results: : We show that homozygous Igf1-/- mice, by postnatal age of 360 days (P360) have an almost flat scotopic ERG response; photopic ERG response is detectable, but of very small amplitude. At the same age, heterozygous Igf1-/+ mice still show both scotopic and photopic ERG responses, but a significant decrease in the ERG wave amplitudes is observed, when compared with wt mice. Immunocytochemical analysis show that homozygous Igf-1-/- mice at P360 suffer important structural modifications in the first synapse of the retinal pathway, that affect mainly to the postsynaptic processes from horizontal and bipolar cells. A decrease in bassoon and synaptophysin staining in both rod and cone synaptic terminals points to reduced photoreceptor output to the inner retina. Retinal morphology of the heterozygous Igf1-/+ mice just show small alterations in the horizontal and bipolar cells processes, when comparing with wt mice. Levels of IGF-I levels. A correlation between the serological levels of IGF-I and phenotype manifestations is observed in the heterozygous Igf1-/+ mice.

Conclusions: : The present results support the use of the Igf-1-/- mouse as a new model for the study of human syndromic blindness.

Keywords: retinal degenerations: cell biology • electroretinography: non-clinical • retinal connections, networks, circuitry 
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