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The Journal of Neuroscience, September 2, 2009, 29(35):10809-10819; doi:10.1523/JNEUROSCI.1857-09.2009

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Development/Plasticity/Repair
Setting the Pace for Retinal Development: Environmental Enrichment Acts Through Insulin-Like Growth Factor 1 and Brain-Derived Neurotrophic Factor

Silvia Landi,^1,2 Francesca Ciucci,¹ Lamberto Maffei,^1,4 Nicoletta Berardi,^3,4 and Maria Cristina Cenni⁴

¹Laboratorio di Neurobiologia, Scuola Normale Superiore, I-56100 Pisa, Italy, ²National Enterprise for nanoScience and nanoTechnology, Scuola Normale Superiore and Consiglio Nazionale delle Ricerche (CNR)–Istituto Nazionale di Fisica della Materia, I-56100 Pisa, Italy, ³Department of Psychology, Florence University, 50121 Florence, Italy, and ⁴Institute of Neuroscience CNR, I-56100 Pisa, Italy

Correspondence should be addressed to Silvia Landi, Scuola Normale Superiore–National Enterprise for nanoScience and nanoTechnology, Piazza San Silvestro, 12, I-56100 Pisa, Italy. Email: silvia.landi{at}sns.it

Environmental enrichment strongly affects visual system maturation both at retinal and cortical levels. Which molecular pathways are activated by an enriched environment (EE) to regulate visual system development has not been clarified. Here, we show that early [postnatal day 1 (P1) to P7] insulin-like growth factor 1 (IGF-1) injections in the eyes of non-EE rat pups mimic EE effects both in increasing BDNF levels in the retinal ganglion cell layer at P10 and in determining a more adult-like retinal acuity, assessed with pattern electroretinogram at P25. Blocking IGF-1 action in EE animals during the same early postnatal time window by injecting the IGF-1 receptor antagonist JB1 prevents EE effects both on BDNF expression and on retinal acuity maturation. Reducing BDNF expression in the retina of IGF-1-treated rats prevents IGF-1 effects on retinal acuity development. Finally, we show that tyrosine hydroxylase (TH) expression is increased in the retina of P10 EE and IGF-1-treated rats and that blocking TH expression in EE animals prevents EE from affecting retinal acuity development. Thus, early levels of IGF-1 play a key role in mediating EE effects on retinal development through an action that requires BDNF and involves dopaminergic amacrine cell network.

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Received April 19, 2009; revised July 7, 2009; accepted July 14, 2009.

Correspondence should be addressed to Silvia Landi, Scuola Normale Superiore–National Enterprise for nanoScience and nanoTechnology, Piazza San Silvestro, 12, I-56100 Pisa, Italy. Email: silvia.landi{at}sns.it

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