Project 02
Targeting of diabetic retinopathy by miRNA in a human retinal organoid model.
Diabetic retinopathy is an increasing global health condition which will rise to 629 million affected by 2045.
Limitations in the treatment of DR require the development of new therapeutic strategies urgently. In the retina, noncoding miRNA plays an integral role in regulating apoptosis, inflammatory responses, visual perception, and photo-transduction, with altered levels reported in diseased states.
In age-related macular degeneration and diabetic retinopathy, miRNA has been implicated in the regulation of angiogenesis, oxidative stress, immune response, and inflammation. To this end, we will use human retinal organoids (co-cultured with endothelial cells) to model DR. Then we will apply miRNAs which have had neuroprotective influence on mouse retinal in vitro.
After miRNAs therapy, functional improvement of diabetic-induced human retinal organoid degeneration will be investigated.
By multi-electrode array chip electrophysiology via giving light ON and OFF stimuli. By inhibition of inhibitory and excitatory neurotransmitters the underlying neural mechanisms involved will be identified as it is proposed the increased activity of ON retinal pathway is mainly a result of reduced inhibitory upstream signalling in diabetes. Furthermore, the improvement of morphological functions of the organoids will be assessed by microscopy e.g. electron and confocal microscopies as well as neuroprotective targeted genes will be tested by RNA-Seq. It expected such therapies prompt the functions of diabetic-induced human retinal organoid degeneration e.g. light ON and OFF responses as well as morphological functions e.g. survival of retinal cells.
Expected results
In vitro proof-of-concept for miRNA therapy for the treatment of DR in retinal human models.
Planned secondments
- B7, supervisor: Aileen Murphy
Purpose: business and economic training - B1 supervisor: Jorge Barcia
Purpose: exosome extraction - AP7, supervisor: Beatriz Llamusí
Purpose: business training