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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-84338-y |
| _version_ | 1831833813190180864 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T04:01:33Z |
| format | Article |
| id | doaj.art-d4a0d9fdf0174c559e718bd7915cc529 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-23T04:01:33Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d4a0d9fdf0174c559e718bd7915cc5292022-12-21T18:00:44ZengNature PortfolioScientific Reports2045-23222021-03-0111111810.1038/s41598-021-84338-yRNA-seq and GSEA identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopiaLoretta Giummarra Vocale0Sheila Crewther1Nina Riddell2Nathan E. Hall3Melanie Murphy4David Crewther5Department of Psychology and Counselling, La Trobe UniversityDepartment of Psychology and Counselling, La Trobe UniversityDepartment of Psychology and Counselling, La Trobe UniversityDepartment of Psychology and Counselling, La Trobe UniversityDepartment of Psychology and Counselling, La Trobe UniversityDepartment of Psychology and Counselling, La Trobe UniversityAbstract 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.https://doi.org/10.1038/s41598-021-84338-y |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-84338-y |
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