In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy

Abstract Diabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-S...

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Autores principales:	Kolja Becker, Holger Klein, Eric Simon, Coralie Viollet, Christian Haslinger, German Leparc, Christian Schultheis, Victor Chong, Markus H. Kuehn, Francesc Fernandez-Albert, Remko A. Bakker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9fb6f6678a93448d8e4b0bd4c4ef2942
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spelling	oai:doaj.org-article:9fb6f6678a93448d8e4b0bd4c4ef29422021-12-02T15:45:16ZIn-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy10.1038/s41598-021-88698-32045-2322https://doaj.org/article/9fb6f6678a93448d8e4b0bd4c4ef29422021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88698-3https://doaj.org/toc/2045-2322Abstract Diabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-Sequencing, we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 43 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP–PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. While previously considered primarily a vascular disease, attention in DR has shifted to additional mechanisms and cell-types. Our findings offer an unprecedented and unbiased insight into molecular pathways and cell-specific changes in the development of DR, and provide potential avenues for future therapeutic intervention.Kolja BeckerHolger KleinEric SimonCoralie ViolletChristian HaslingerGerman LeparcChristian SchultheisVictor ChongMarkus H. KuehnFrancesc Fernandez-AlbertRemko A. BakkerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kolja Becker Holger Klein Eric Simon Coralie Viollet Christian Haslinger German Leparc Christian Schultheis Victor Chong Markus H. Kuehn Francesc Fernandez-Albert Remko A. Bakker In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy
description	Abstract Diabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-Sequencing, we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 43 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP–PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. While previously considered primarily a vascular disease, attention in DR has shifted to additional mechanisms and cell-types. Our findings offer an unprecedented and unbiased insight into molecular pathways and cell-specific changes in the development of DR, and provide potential avenues for future therapeutic intervention.
format	article
author	Kolja Becker Holger Klein Eric Simon Coralie Viollet Christian Haslinger German Leparc Christian Schultheis Victor Chong Markus H. Kuehn Francesc Fernandez-Albert Remko A. Bakker
author_facet	Kolja Becker Holger Klein Eric Simon Coralie Viollet Christian Haslinger German Leparc Christian Schultheis Victor Chong Markus H. Kuehn Francesc Fernandez-Albert Remko A. Bakker
author_sort	Kolja Becker
title	In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy
title_short	In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy
title_full	In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy
title_fullStr	In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy
title_full_unstemmed	In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy
title_sort	in-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9fb6f6678a93448d8e4b0bd4c4ef2942
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In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy

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