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RNA-seq and GSEA identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopia

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posted on 28.04.2021, 02:54 by Loretta Giummarra, Sheila CrewtherSheila Crewther, Nina RiddellNina Riddell, NE Hall, Melanie MurphyMelanie Murphy, David CrewtherDavid Crewther
Currently there is no consensus regarding the aetiology of the excessive ocular volume that characterizes high myopia. Thus, we aimed to test whether the gene pathways identified by gene set enrichment analysis of RNA-seq transcriptomics refutes the predictions of the Retinal Ion Driven Efflux (RIDE) hypothesis when applied to the induction of form-deprivation myopia (FDM) and subsequent recovery (post-occluder removal). We found that the induction of profound FDM led to significant suppression in the ligand-gated chloride ion channel transport pathway via suppression of glycine, GABA and GABA ionotropic receptors. Post-occluder removal for short term recovery from FDM of 6 h and 24 h, induced significant upregulation of the gene families linked to cone receptor phototransduction, mitochondrial energy, and complement pathways. These findings support a model of form deprivation myopia as a Cl ion driven adaptive fluid response to the modulation of the visual signal cascade by form deprivation that in turn affects the resultant ionic environment of the outer and inner retinal tissues, axial and vitreal elongation as predicted by the RIDE model. Occluder removal and return to normal light conditions led to return to more normal upregulation of phototransduction, slowed growth rate, refractive recovery and apparent return towards physiological homeostasis. A C −

Funding

2007 NHMRC Development Grant and ARC Discovery Project (DP110103784).

History

Publication Date

01/12/2021

Journal

Scientific Reports

Volume

11

Issue

1

Article Number

ARTN 5280

Pagination

18p.

Publisher

Springer Nature

ISSN

2045-2322

Rights Statement

The Authors reserves all moral rights over the deposited text and must be credited if any re-use occurs.

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