Metabolic adaptation and neuroprotection differ in the retina and choroid in a piglet model of acute postnatal hypoxia

Autores de IIS La Fe

• Justo Javier Escobar Cubiella

  Autor

• Máximo Vento Torres

  Autor

• Raquel Escrig Fernández

  Autor

• Guillermo Quintas Soriano

  Autor

• Juan J. Sastre Belloch

  Autor

Participantes ajenos a IIS La Fe

• Arduini A
• Saugstad OD
• Solberg R

Grupos

• Perinatología

Abstract

BACKGROUND: Hypoxic-ischemic insults to the neonatal brain may cause neurodevelopmental disorders. Vulnerability of different areas of the neural tissue to hypoxic-ischemic stress might be explained by either heterogeneous sensitivity to oxygen or neuroprotective capability. Our understanding of regional heterogeneity is still incomplete in terms of metabolic reconfiguration and/or activation of neuroprotective mechanisms. METHODS: We studied, by western blotting, reversetranscriptase PCR, and tandem mass spectrometry, the response of retina and choroid at protein, gene, and metabolic levels during hypoxia in a piglet model of acute postnatal hypoxia. RESULTS: We evidenced a metabolic shift towards glycolysis in choroid after hypoxia while retina experienced a dramatic energy stress with decreased mitochondrial metabolites. Hypoxia-inducible transcription factor-1 alpha (HIF-1 alpha) was not stabilized in retina during hypoxia, supported by a deficient signaling from v-akt murine thymoma viral oncogene (AKT) and ERK1/2, and unchanged glutathione redox status. In retina, but not in choroid, phosphorylation of p65 (NF-kappa B) and increased transcription of target genes may have a major role during hypoxic stress. CONCLUSION: We showed that the retina engages a distinct pattern of signaling and transcriptional events than observed in the choroid. Retina and choroid may reflect regional sensitivity to hypoxia. While prolonged and intense hypoxia may jeopardize retinal cell survival, choroid sets up a different pattern of response, which promotes adaptation to these adverse conditions.

Keywords

• NF-KAPPA-B; GENE-EXPRESSION; STAT3 ACTIVATION; SURVIVAL FACTOR; NEONATAL-RATS; BRAIN-INJURY; BLOOD-FLOW; ADRENOMEDULLIN; CELLS; HIF-1