title: Age-related functional and structural retinal modifications in the Igf1-/- null mouse.
abstract: BACKGROUND
  Mutations in the gene encoding human insulin-like growth factor-I (IGF-I) cause syndromic neurosensorial deafness. To understand the precise role of IGF-I in retinal physiology, we have studied the morphology and electrophysiology of the retina of the Igf1(-/-) mice in comparison with that of the Igf1(+/-) and Igf1(+/+) animals during aging.
  
  
  METHODS
  Serological concentrations of IGF-I, glycemia and body weight were determined in Igf1(+/+), Igf1(+/-) and Igf1(-/-) mice at different times up to 360days of age. We have analyzed hearing by recording the auditory brainstem responses (ABR), the retinal function by electroretinographic (ERG) responses and the retinal morphology by immunohistochemical labeling on retinal preparations at different ages.
  
  
  RESULTS
  IGF-I levels are gradually reduced with aging in the mouse. Deaf Igf1(-/-) mice had an almost flat scotopic ERG response and a photopic ERG response of very small amplitude at postnatal age 360days (P360). At the same age, Igf1(+/-) mice still showed both scotopic and photopic ERG responses, but a significant decrease in the ERG wave amplitudes was observed when compared with those of Igf1(+/+) mice. Immunohistochemical analysis showed that P360 Igf1(-/-) mice suffered important structural modifications in the first synapse of the retinal pathway, that affected mainly the postsynaptic processes from horizontal and bipolar cells. A decrease in bassoon and synaptophysin staining in both rod and cone synaptic terminals suggested a reduced photoreceptor output to the inner retina. Retinal morphology of the P360 Igf1(+/-) mice showed only small alterations in the horizontal and bipolar cell processes, when compared with Igf1(+/+) mice of matched age.
  
  
  CONCLUSIONS
  In the mouse, IGF-I deficit causes an age-related visual loss, besides a congenital deafness. The present results support the use of the Igf1(-/-) mouse as a new model for the study of human syndromic deaf-blindness.
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, CIBERER Unit 761, ISCiii, IdiPAZ, Arturo Duperier 4, 28029 Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Rodriguez-de la Rosa
authors.forename: L
authors.initials: L
authors.lastname: Fernandez-Sanchez
authors.forename: F
authors.initials: F
authors.lastname: Germain
authors.forename: S
authors.initials: S
authors.lastname: Murillo-Cuesta
authors.forename: I
authors.initials: I
authors.lastname: Varela-Nieto
authors.forename: P
authors.initials: P
authors.lastname: de la Villa
authors.forename: N
authors.initials: N
authors.lastname: Cuenca
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology* / Q000502:physiology*; D000818:Animals; D003638:Deafness / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004596:Electroretinography / Q000379:methods; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D012160:Retina / Q000473:pathology* / Q000502:physiology*; D014786:Vision Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I