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Sheila Crewther, Loretta Giummarra, Melanie Murphy; Gene Expression Studies implicate Physiological Stress in Form Deprivation Myopia. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3674.
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© ARVO (1962-2015); The Authors (2016-present)
Myopia is the commonest visual disorder and a risk factor for most disorders leading to visual compromise, yet the aetiology remains elusive. Thus we aimed to examine the gene expression changes underlying the morphological, ultrastructural and physiological changes previously described, that suggest severe physiological stress in the form deprived chick model.
Methods: Ten male hatchling chicks of which 6 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).
At a FC>2.5, 309 genes were up- and 352 down-regulated with Sorcin, a calcium binding protein showing a FC of +31.3 change while acetylcholinesterase showed a FC of -10.5. Unlike previous studies in this area we have extended our analyses to include ontological (functional) pathways that may be involved in these observed changes. The GSEA algorithm identified downregulation of genes associated with cell structure and integrity and genomic strain. An increase in cell metabolism was noted, specifically, fatty acid oxidation as the main source of energy in these tissues.
The pathways associated with the myopic pathophysiology include diminished glucose metabolism, cellular stress responses and cell volume control. All pathways are indicative of physiological stress and diminished ability to maintain retinal homeostasis after a week of form deprivation. The pathways include most genes described in previous studies. Human SNP research is also inconsistent but mostly identifies extracellular matrix genes that offer no indication of the mechanism underlying myopia progression.
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