Project 01
miRNA expression, identification, and functional characterization under oxidative stress challenge in diabetic retinopathy.
Recently, the interest on the role of miRNAs in different diseases is rising.
These sequences can inhibit the expression of different gene families (antioxidant machinery, inflammation, autophagy...), thus, miRNAs are considered new targets for therapeutic approaches. Dr Barcia and his team identified several miRNAs expressed by ARPE-19 under oxidative conditions and then studied the potential pathways associated to these miRNAs.
Approach
The present project is supported by the Ministerio de Innovación y Ciencia SPAIN (MICIN) Grant PID2020-117875GB-I00. The project is based on previous works of the applicant group where cells of the RPE present certain miRNAs (miR-302a, miR-205-5p and miR-122, among others) under-expressed in oxidative stress situations, as occurs in DR and AMD. Furthermore, this downregulation results in an increase of VEGF and therefore in an aggravated growth of retinal capillaries. We propose the use of some miRNAs mimics as antiangiogenic therapy in DR and AMD.
The beneficial effect of miRNAs miR-302a, miR-205-5p and miR-122, will be assessed.
The latest miRNAs, miR-302a and miR-122, travel inside extracellular vesicles and will be observed with greater attention, in order to assess whether they could have a potential role as indicators of the advancement of neovascularization or even diagnostic value in the future. Eventually, the study will be completed with experiments using miRNAs silencers. After the in vitro study, selected miRNAs will be analyzed in murine model samples in order to establish a correlation between specific miRNAs and its implication in the retinal neurodegeneration processes. Moreover, experiments with tissue from human patients are planned to observe the behaviour of those miRNAs in the eye.
Expected results
- To establish a correlation between specific miRNAs (miR-302a, miR-205-5p and miR-122) and their implication in the retinal neurodegeneration processes
- Identify new miRNA targets for therapeutic approaches
- Identify miRNAs predictive biomarkers
Planned secondments
- B2, supervisor: Zohreh Hosseizadeh
Purpose: treatment of retinal organoids - AP7, supervisor: Beatriz Llamusí
Purpose: business training - B7, supervisor: Aileen Murphy
Purpose: economic training