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

Abstract 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 Eff...

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Autores principales:	Loretta Giummarra Vocale, Sheila Crewther, Nina Riddell, Nathan E. Hall, Melanie Murphy, David Crewther
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d4a0d9fdf0174c559e718bd7915cc529
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spelling	oai:doaj.org-article:d4a0d9fdf0174c559e718bd7915cc5292021-12-02T15:52:59ZRNA-seq and GSEA identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopia10.1038/s41598-021-84338-y2045-2322https://doaj.org/article/d4a0d9fdf0174c559e718bd7915cc5292021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84338-yhttps://doaj.org/toc/2045-2322Abstract 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, GABAA and GABAC 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.Loretta Giummarra VocaleSheila CrewtherNina RiddellNathan E. HallMelanie MurphyDavid CrewtherNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Loretta Giummarra Vocale Sheila Crewther Nina Riddell Nathan E. Hall Melanie Murphy David Crewther RNA-seq and GSEA identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopia
description	Abstract 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, GABAA and GABAC 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.
format	article
author	Loretta Giummarra Vocale Sheila Crewther Nina Riddell Nathan E. Hall Melanie Murphy David Crewther
author_facet	Loretta Giummarra Vocale Sheila Crewther Nina Riddell Nathan E. Hall Melanie Murphy David Crewther
author_sort	Loretta Giummarra Vocale
title	RNA-seq and GSEA identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopia
title_short	RNA-seq and GSEA identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopia
title_full	RNA-seq and GSEA identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopia
title_fullStr	RNA-seq and GSEA identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopia
title_full_unstemmed	RNA-seq and GSEA identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopia
title_sort	rna-seq and gsea identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d4a0d9fdf0174c559e718bd7915cc529
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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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