Abstract
PurposeRNA sequencing analysis has demonstrated bidirectional changes in metabolism, structural and immune pathways during early induction of defocus induced myopia. Thus, the aim of this study was to investigate whether similar gene pathways are also related to the more excessive axial growth, ultrastructural and elemental microanalytic changes seen during the induction and recovery from form-deprivation myopia (FDM) in chicks and predicted by the RIDE model of myopia.MethodsArchived genomic transcriptome data from the first three days of induction of monocularly occluded form deprived myopia (FDMI) in chicks was obtained from the GEO database (accession # GSE6543) while data from chicks monocularly occluded for 10 days and then given up to 24 h of normal visual recovery (FDMR) were collected. Gene set enrichment analysis (GSEA) software was used to determine enriched pathways during the induction (FDMI) and recovery (FDMR) from FD. Curated gene-sets were obtained from open access sources.ResultsClusters of significant changes in mitochondrial energy metabolism, neurotransmission, ion channel transport, G protein coupled receptor signalling, complement cascades and neuron structure and growth were identified during the 10 days of induction of profound myopia and were found to correlate well with change in axial dimensions. Bile acid and bile salt metabolism pathways (cholesterol/lipid metabolism and sodium channel activation) were significantly upregulated during the first 24 h of recovery from 10 days of FDM.ConclusionsThe gene pathways altered during induction of FDM are similar to those reported in defocus induced myopia and are established indicators of oxidative stress, osmoregulatory and associated structural changes. These findings are also consistent with the choroidal thinning, axial elongation and hyperosmotic ion distribution patterns across the retina and choroid previously reported in FDM and predicted by RIDE.
Highlights
Myopia is the most common visual disorder worldwide and the greatest risk factor for many severe ophthalmic diseases in older individuals (Dolgin, 2015)
We believe our analyses demonstrate that Gene Set Enrichment Analysis (GSEA) is a valuable tool in identifying altered biological pathways in the chick model of refractive error, as well as providing greater statistical power in identifying biological pathways not otherwise considered to be of potential significance
A major strength with GSEA is the generation of further hypotheses related to the understanding that many genes within a biological pathway can contribute to the underlying biology of a disease (Tripathi, Glazko & Emmert-Streib, 2013)
Summary
Myopia (short-sightedness) is the most common visual disorder worldwide and the greatest risk factor for many severe ophthalmic diseases in older individuals (Dolgin, 2015). Chicken, form-deprivation (FD) is characterised by rapid ocular growth and development of myopia via dramatic increases in vitreous chamber volume (Wallman, Turkel & Trachtman, 1978), reduced choroidal blood flow and concurrent choroidal and retinal thinning (Shih et al, 1993; Shih, Fitzgerald & Reiner, 1993a; Shih, Fitzgerald & Reiner, 1993b) (and as shown with the MRI photomicrograph in Fig. 1), similar to that seen in profound human myopia (Borish, 1949; Feldman et al, 1991; Morgan, Ohno-Matsui & Saw, 2012; Moriyama et al, 2007; Yang & Koh, 2015; Zhang & Wildsoet, 2015)
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