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Loretta Giummarra, Nina Riddell, Nathan Hall, Melanie Murphy, Sheila Gillard Crewther; Transcriptome Analysis Indicates Adaptive Responses to Physiological Stress in Recovery from FDM. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2163.
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© ARVO (1962-2015); The Authors (2016-present)
Form deprivation myopia (FDM) is associated with dramatic increases in ocular volume, axial length, thinning of the retina and choroid and hyperosmotic stress. Thus this study aimed to assess the associated gene pathway changes using high throughput RNA-sequencing and comprehensive bioinformatic analysis. Given our previous ultrastructural and elemental microanalyses it was hypothesized that profile changes would involve energy metabolism, ionic solute changes and evidence of oxidative stress
Twelve male hatchling chicks were monocularly occluded from days 4-11 after which chicks were given T=0hr, T=6hr or T=24hr of normal vision. Four chicks were used as aged-matched unoccluded controls. Biometrics were measured prior to tissue collection. RNA was isolated from choroid/retina/RPE tissue and prepared for sequencing on the Illumina HiSeq™ 1500. Raw reads were mapped onto the chicken genome and counts determined for each gene. Differential expression analysis was undertaken with voom/EdgeR with an FDR of 0.05. Gene Set Enrichment Analysis (GSEA) software was used to determine whether a priori defined set of genes were significantly altered (FDR<0.25) during the induction and recovery of FDM. Curated gene sets were obtained from BioCarta, KEGG, and the Pathway Interaction Database and the Reactome database.
FD Chicks were ~20D myopic. Refractive normalization began with removal of occlusion. GSEA analysis revealed an overall suppression in genes associated with metabolism and ion homeostasis at T=0hr. GSEA during the recovery period revealed an increase in expression of genes associated with glucose metabolism, potassium transport and hypoxia. These changes were positively correlated with reduction in refraction.
Increased axial growth during FD is accompanied by suppression of gene pathways associated with retinal metabolism and refractive normalization. Removal of FD and reintroduction of the normal visual environment with constantly changing luminance levels requires upregulation of metabolic pathways and normalization of ion distribution profiles across the eye. These results confirm our previous work and build our understanding of the importance of osmoadaptive pathways that use energy metabolism, ion transport, to reduce hypoxia and restore osmotic homeostasis.
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