Abstract
Background and aims: Low oxygen level and reactive oxygen species promote stabilization of HIF-1α, which in turn increases the expression of genes involved in angiogenesis (VEGFa, VEGFR1) and metabolism (GAPDH, ALDOC, PGK-1). VEGFa and VEGFR1 play a crucial role in the neovascularization of the retina. VEGFR2 mediates the major cellular responses induced by VEGF, and also plays a role in neuroprotection.
Methods: Hypoxia was induced in newborn piglets. Retina and choroidea were obtained at end-hypoxia or after 15 min resuscitation with 21% or 100% oxygen. Control animals were kept anesthetized and ventilated. Gene expression of VEGFa, VEGFR1, VEGFR2, BDNF, ALDOC, GAPDH, PGK1 and HIF-1α was determined in retina and choroidea by RT- PCR.
Results: There was a two-threefold increase in Vegfa expression in both retina and choroidea during hypoxia and after 15 min reoxygenation (p< 0.01 vs control). Vegfr2 expression was decreased by 50% (p< 0.05 vs control) in retina and choroidea. Aldoc decreased by 75% in choroid (p< 0.001) and 25% in retina (p< 0.05) after hypoxia and resuscitation. Pgk1 was increased by 25% just in retina (p< 0.05 vs control). Hif-1a mRNA level was not changed after hypoxia or resuscitation, as also observed for Vegfr1, Gapdh, Pgk1(in choroidea) and Bdnf (p>0.05 vs control).
Conclusions: Low PO2 is responsible for adaptive responses both in retina and choroidea. The increase in the angiogenic factor VEGFa was not paralleled by the increase in other HIF-1 target genes. Repression of ALDOC may have important physiological significance, possibly to enhance the antioxidant defense.
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Solberg, R., Arduini, A., Escobar, J. et al. 34 Early Gene Regulation in Retina and Choroid After Ashpyxia and Resuscitation in Newborn Piglets. Pediatr Res 68 (Suppl 1), 20 (2010). https://doi.org/10.1203/00006450-201011001-00034
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DOI: https://doi.org/10.1203/00006450-201011001-00034