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Sheila G. Crewther, Loretta Guimmarra, Melanie J. Murphy; PAS Domain Genes in Form Deprivation Myopia. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3448.
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© ARVO (1962-2015); The Authors (2016-present)
Form deprivation myopia is associated with dramatic increases in eye volume, thinning of the retina and choroid and ultrastructural changes that are indicative of physiological stress. We used gene expression microarrays and pathway and ontological analysis to provide an understanding of the collective behaviour of genes and in particular to probe the behaviour of PAS domain proteins that are known to regulate circadian rhythm and respond to hypoxia. To date a particular role for PAS domain genes in optical defocus has not been investigated.
Thirty male hatchling chicks of which 13 were occluded to induce form-deprivation (FD) myopia by attaching a translucent polystyrene occluder to the periocular feathers of their right eye from day 3 - 10. Choroid/retina/RPE preparations were taken from the posterior eye cup, placed in RNA stabilizing buffer and transferred to -20°C freezer. For Affymetrix microarrays, samples were pooled and analysis was conducted using the one-cycle process (The Australian Genome Research Facility LTD; Walter and Eliza Hall Institute, Victoria, Australia). Data was exported as .cel files containing probe level intensities and analysed using Pathway Studio 8.0 (Ariadne Genomics Inc, Rockville, MD, USA). Gene Set Enrichment Analysis (GSEA) using the Kolmogrov-Smirnov test algorithm to identify statistically enriched (p<0.05) Gene Ontologies (GO) as well as Ariadne Ontologies (AO), Ariadne Signalling Pathways (ASP) and Ariadne Metabolic Pathways (AMP).
We identified 3110 differentially expressed genes that satisfied a fold-change of >1.5. We refined the cut-off to >2.5 and reduced the number of significant genes to 510. PAS domain proteins and Cl, K and Na transport/ homeostasis were significantly downregulated ontologies.
Downregulated expression of PAS domain and ion transport genes supports the notion that the FD eye is under physiological stress specifically resulting from prolonged hypoxia. Altered ion channel regulation also supports the Ionically driven Fluid hypothesis where the prolonged reduction in luminance modulation during FD has been associated with osmoregulatory changes and perturbed transretinal fluid movements.
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