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Nina Riddell, Loretta Giummarra, Nathan Hall, Melanie Murphy, David P Crewther, Sheila Gillard Crewther; RNAseq gene expression analysis highlights the correlation of changes in metabolic and structural pathways with axial elongation during refractive compensation.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2164.
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© ARVO (1962-2015); The Authors (2016-present)
High throughput transcriptome studies in animal models of refractive error have primarily analysed data at the single-gene level. Results from these studies are disparate and a comprehensive framework for understanding the biological cascades underlying ocular growth regulation remains elusive. Thus, this study aimed to identify characteristic biological features of refractive compensation to myopic and hyperopic defocus in chick by correlating axial length across lens-groups during defocus induction with expression of genes in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.
Chicks were raised with ±10D lenses, or no lens. Following biometric measurements at 1, 2, and 3 days, 3-4 chicks per lens-group were euthanized and RNA extracted from the retina/RPE/choroid. Libraries were sequenced on the Illumina HiSeq1500, raw reads mapped to the chick genome, and counts determined for each gene. Counts/million were imported into GSEA and expression of KEGG pathways correlated with axial length phenotype across lens-groups at each time-point (FDR cut-off <.25).
Refractive and axial length change was rapid during the first day of defocus for both lens-types and slower over subsequent days (particularly for plus lenses). Consistent with the initially rapid change in ocular morphology, expression of structural pathways including focal adhesion, tight junction, and vascular smooth muscle contraction was positively correlated with axial length at 1 day. Fatty acid metabolic and signalling pathways were also correlated with axial length at this time. Although no structural pathways were identified following 2 and 3 days of lens-wear when morphological changes had slowed, metabolic pathways (such as oxidative phosphorylation) were implicated at both time-points.
This study is the first to correlate ocular axial length changes with pathway enrichment across a period of refractive compensation to lenses. Results suggest that changes in structural pathway expression are linked to periods of rapid axial growth change. Perturbed metabolism was characteristic of all stages of compensation, with implication of oxidative phosphorylation and related pathways suggesting that growth changes elicit a shift in energy homeostasis that may alter redox state and vulnerability to later development of ocular pathologies.
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