|
| Status |
Public on Jan 11, 2023 |
| Title |
Transcriptomic analysis reveals retinal neuromodulation by sitagliptin in an experimental model of diabetic retinopathy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The aim of the study was to explore the effect of topically administered sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4, on the retinal expression patterns of an experimental model of DR.
Background: Synaptic dysfunction and neuronal damage have been extensively associated with diabetic retinopathy (DR). Our group evidenced that chronic hyperglycemia reduces the retinal expression of presynaptic proteins, which are crucial for a proper synaptic function. The aim of the study was to explore the effect of topically administered sitagliptin, an inhibitor of the en-zyme dipeptidyl peptidase-4, on the retinal expression patterns of an experimental model of DR. Methods: Transcriptome analysis was performed comparing the retinas of 10 diabetic (db/db) mice randomly treated with sitagliptin eye drops (10 mg/mL) twice daily, and the reti-nas of 10 additional db/db mice that received vehicle eye drops. 10 non diabetic mice (db/+) were used as control group. Gene Ontology (GO) and Reactome databases were used to assess the Gene Set Enrichment Analysis (GSEA) in order to explore the most enriched biological pathways among groups. The most differentiated genes of these pathways were validated through quantitative RT-PCR. Results: Transcriptome analysis revealed that sitagliptin eye drops have a significant effect on retinal expression patterns and that neurotransmission was the most enriched biological process. Our study evidenced enriched pathways that contain genes involved in membrane trafficking, transmission across chemical synapses, vesi-cle-mediated transport, neurotransmitter receptors and postsynaptic signal transmission with negative regulation of signaling as a consequence of neuroprotector treatment with sitagliptin. This improves the modulation of macromolecule biosynthetic process with positive regulation of cell communication which provides beneficial effects for neuronal metabolism. Conclu-sions: This study suggests that topical administration of sitagliptin ameliorates the abnormali-ties on presynaptic and postsynaptic signal transmission during experimental DR, and that this improvement is one of the main mechanisms behind the previously demonstrated beneficial effects.
|
| |
|
| Overall design |
Transcriptome analysis was performed comparing the retinas of 10 diabetic (db/db) (BKS.Cg-Dock7m +/+ Leprdb/J) mice randomly treated with sitagliptin eye drops (10 mg/mL) twice daily, and the retinas of 10 additional db/db mice that received vehicle eye drops. 10 non diabetic mice (db/+) (BKS.Cg-Dock7m + Leprdb/+) were used as control group. The mice were obtained from Charles River Laboratories Inc (Calco Italy for the study). The study is based on 30 samples (the 10 highest quality RNA samples of each group) hybridized in Clariom S Mouse Arrays (ThermoFisher Scientific, Waltham, MA, USA). Bioinformatics analysis has been carried out in the Statistics and Bioinformatics Unit (UEB) at VHIR.
|
| |
|
| Contributor(s) |
Bogdanov P, Ramos H, Deàs-Just A, Simó R, Hernández C |
| Citation(s) |
36614016 |
| Submission date |
Nov 30, 2022 |
| Last update date |
Jan 12, 2023 |
| Contact name |
Patricia Bogdanov |
| E-mail(s) |
patricia.bogdanov@vhir.org
|
| Organization name |
Vall d'Hebron Research Institute
|
| Department |
Diabetes Research and Metabolism Unit
|
| Lab |
Collserola Building, Laboratory 144
|
| Street address |
Passeig de la Vall d'Hebron 119-129 Collserola Building. Lab 144
|
| City |
Barcelona |
| State/province |
Barcelona, Spain |
| ZIP/Postal code |
08035 |
| Country |
Spain |
| |
|
| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
|
| Samples (29)
|
|
| Relations |
| BioProject |
PRJNA907000 |
Less...
More...