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