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Series GSE172138 Query DataSets for GSE172138
Status Public on Mar 03, 2023
Title Retinal organoids provide a suitable tool for toxicological drug screening – a comprehensive study validating well-known drug effects on retinal organoids
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Drug toxicity screening on retina is essential for the development of safe therapies for a large number of diseases, whilst preserving visual acuity and function. To this end, retinal organoids derived from human pluripotent stem cells (hPSCs) provide a suitable screening platform due to their similarity to human retina and the ease of generation in large-scale formats, offering almost unlimited excess of tissue. Two hPSC cell lines were differrentiated to retinal organoids which comprised all key retinal cell types in multiple nuclear and synaptic layers, enabling the maintenance of retinal ganglion and bipolar cells and moreover allowed the development of subtypes as revealed by the single cell RNA-Seq analysis. Ketorolac, Digoxin, Thioridazine, Sildenafil, Ethanol and Methanol were used to screen drug effects on retinal organoids. Exposure of the hPSC-derived retinal organoids to Diogxin, Thioridazine and Sildenafil exposure resulted in photoreceptor cell death, while Digoxin and Thioridazine additionally affected all other cell types, including Müller glia cells. Ethanol and Methanol caused an upregulation in retinal ganglion cell related geneexpression. All drug treatments activated astrocytes, indicated by dendrites sprouting into neuroepithelium and upregulation of astrocyte related genes. The ability to resond to light was presereved in organoids although the number of active retinal ganglion cells decreased after drug expsoure. These data indicate comparable drug effects in organoids to those reported in in vitro models and/or in humans, thus providing first robust experimental evidence of their suitability for toxicological studies.
Overall design Retinaol organoids were cultured till day 200 of differerntiation, followed by drug exposure for 24 h, except for Sildenafil. Incubation was 7 days for Sildenafil treatment. Drugs tested were: Digoxin (40nM), Thioridazine (135uM), Sildenafil (225uM), Ethanol (500mM), Methanol (0.4%) and Ketorolac (2.5mM). The vehicle control was treated with PBS.
Contributor(s) Lako M, Dorgau B, Collin J, Queen R
Citation(s) 35298655
Submission date Apr 15, 2021
Last update date Jun 28, 2023
Contact name Majlinda Lako
Organization name Newcastle University
Department Institute of Genetic Medicine and Institute for Ageing
Street address International Centre for Life, Central Parkway
City Newcastle Upon Tyne
ZIP/Postal code NE1 3 BZ
Country United Kingdom
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (7)
GSM5242603 AD4_Control
GSM5242604 AD4_Digoxin
GSM5242605 AD4_Ethanol
BioProject PRJNA722233
SRA SRP314952

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Supplementary file Size Download File type/resource
GSE172138_counts.txt.gz 83.6 Mb (ftp)(http) TXT
GSE172138_embeddings.txt.gz 803.8 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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