In:
Acta Ophthalmologica, Wiley, Vol. 97, No. S263 ( 2019-12)
Abstract:
In this study, single‐cell transcriptomics was applied to provide insight into cell‐type specific transcriptional dynamics in the neuronal, glial, vascular and inflammatory compartments of the Akimba retina. Investigation of the molecular characteristics and networks underlying the pathobiology of this diabetic retinopathy mouse model might lead to the identification of new pathophysiological or protective mechanisms. Methods Retinas were isolated from 12‐week‐old Akimba (Ins2 Akita VEGF +/‐ ) and age‐matched wild type (WT) C57BL/6J mice and dissociated by collagenase treatment into single cell suspension. Single‐cell barcoded libraries were generated (10× Genomics) and sequenced on the Illumina HiSeq4000 platform. After data pre‐processing, principal component analysis‐based clustering was performed, and clusters were annotated based on marker genes. In addition, differential expressed genes between Akimba and WT retinal cells were further analyzed for statistically enriched pathways and categorized for biological function using STRING. Results Our results showed that neuronal cell death, especially of the rod photoreceptors, is accompanied by an immune response in the Akimba versus WT retina. This is demonstrated by the prominent increase in and activation of resident and invading immune cells and enrichment of e.g. complement, interferon and inflammasome signaling pathways. Transcriptional changes in macroglia point towards their attempt to rescue lost tissue via reactive gliosis, and towards a metabolic shift from glycolysis to oxidative phosphorylation. In addition, the Akimba retina is also characterized by an overall change in ribosome synthesis and translation, oxidative stress responses and metal dyshomeostasis. Conclusion Our data indicate substantial shifts in abundance of cell types in the Akimba retina, and cell‐specific changes that may lead to functional uncoupling of neuron‐glia interactions.
Type of Medium:
Online Resource
ISSN:
1755-375X
,
1755-3768
DOI:
10.1111/aos.v97.s263
DOI:
10.1111/j.1755-3768.2019.5291
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2466981-7
detail.hit.zdb_id:
2408333-1
