Journal article
In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy
Scientific reports, Vol.11(1), pp.10494-10494
05/18/2021
DOI: 10.1038/s41598-021-88698-3
PMCID: PMC8131353
PMID: 34006945
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.
Details
- Title: Subtitle
- In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy
- Creators
- Kolja Becker - Biberach an der Riß, GermanyHolger Klein - Biberach an der Riß, GermanyEric Simon - Biberach an der Riß, GermanyCoralie Viollet - Biberach an der Riß, GermanyChristian Haslinger - Vienna, AustriaGerman Leparc - Biberach an der Riß, GermanyChristian Schultheis - Biberach an der Riß, GermanyVictor Chong - Therapeutic Area CNS Retinopathies Emerging Areas, BI International GmbH, Ingelheim, GermanyMarkus H Kuehn - Iowa City, IA USAFrancesc Fernandez-Albert - Biberach an der Riß, GermanyRemko A Bakker - Biberach an der Riß, Germany
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.11(1), pp.10494-10494
- DOI
- 10.1038/s41598-021-88698-3
- PMID
- 34006945
- PMCID
- PMC8131353
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- Nature Publishing Group UK
- Grant note
- ;
- Language
- English
- Date published
- 05/18/2021
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9984101222402771
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