Age-related functional and structural retinal modifications in the Igf1−/− null mouse

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Title: Age-related functional and structural retinal modifications in the Igf1−/− null mouse
Authors: Rodríguez de la Rosa, Lourdes | Fernández Sánchez, Laura | Germain Martínez, Francisco | Murillo Cuesta, Silvia | Varela Nieto, Isabel | Villa Polo, Pedro de la | Cuenca, Nicolás
Research Group/s: Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS)
Center, Department or Service: Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología
Keywords: IGF1 | Retina | Degeneration | Deaf-blindness
Knowledge Area: Biología Celular
Issue Date: 28-Feb-2012
Publisher: Elsevier
Citation: RODRIGUEZ-DE LA ROSA, L., et al. "Age-related functional and structural retinal modifications in the Igf1−/− null mouse". Neurobiology of Disease. Vol. 46, Issue 2 (May 2012). ISSN 0969-9961, pp. 476-485
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 360 days 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 360 days (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.
Sponsor: This research was funded by grants from the Spanish Ministry of Science and InnovationSAF2010-21879 and RETICSRD07/0062/0008 to PdlV; BFU2009-07793/BFI, Fundaluce, ONCE and RETICSRD07/0062/0012 to NC; and SAF2008-0064, SAF2011-24391 and Intra-CIBERER programs to IV-N.
ISSN: 0969-9961 (Print) | 1095-953X (Online)
DOI: 10.1016/j.nbd.2012.02.013
Language: eng
Type: info:eu-repo/semantics/article
Peer Review: si
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Appears in Collections:INV - NEUROVIS - Artículos de Revistas

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