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Sheila G. Crewther, Loretta Giummarra, Melanie J. Murphy-Edwards; Hifs Seeing The Light- Hypoxia Inducible Factors During Recovery From Form Deprivation Myopia. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3924.
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Hypoxia Inducible Factor 1 alpha (HIF1α,) is the transcription regulator of cellular adaptation to low oxygen tension. In hypoxic conditions HIF1 induces transcription of target genes involved in oxygen delivery and energy metabolism. Thus given that the choroid is significantly thinned, choroidal blood flow is reduced and potassium, sodium and chloride ion abundance is altered across the retina and choroid for some time following form deprivation, we hypothesized that hypoxia related gene expression would show predictable changes during early recovery from deprivation.
Hatchling male chicks were raised from day 3-11, with or without a translucent occluder over their right eye. Biometrics were performed before retina/RPE/choroid tissue was isolated at 0h, 6h, and 24h after occluder removal and mRNA prepared from 53 FD and 28 age matched controls for comparison of gene expression by Affymetrix microarray and RT-PCR analysis and protein expression using Western Blots of HIF-1α, HIF-2α, and associated pathway genes VEGF GLUT1, AQP4 and AQP9, Kir4.2 and annexin.
Gene expression for HIF1 and AQP4 and AQP9 was greater and correspondingly lower for HIF2, VEGF, GLUT-1, SGK, Kir4.2 and Annexin 1 (ANAX1) in FD eyes than in controls until near 24 hours post -occlusion. Levels of Potassium/ATP channels also showed rapid upregulation post-occlusion.
HIF1 and potassium channel related genes and proteins show changes in level of expression over the first 24 hours post occlusion, indicative of recovery from mild hypoxia. The changes in hypoxia related gene expression parallel changes in potassium channel expression and previously reported decrease in K+ abundance levels.
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