The World Economic Forum reports 2.5 billion people suffer vision impairment. Poor vision is associated with lower socio-economic status. Ocular disease places a direct economic burden on European countries of ~€20 billion. Vision loss and retinal degeneration (RD) are observed in inherited retinal degeneration (IRD), age-related macular degeneration (AMD) and diabetic retinopathy (DR) patients. Despite advances, critical needs remain to improve surveillance of disease progression, to elucidate common mechanisms underlying disease progression and to develop more effective treatments. Targeting common pathogenic nodes has potential to benefit broader cohorts of RD patients.
Extracellular vesicles (EVs) are small, membrane-bound particles released by cells into the extracellular environment. EVs are found in most biological fluids, including blood, urine, and saliva (PMID: 29339798). EVs play crucial roles in cell-to-cell communication, carrying a diverse cargo of proteins, lipids, and nucleotides which can influence recipient cells, and alter biological processes (e.g. cell death) in
physiology and pathology.
Our hypothesis is that EVs released from retinal cells are common mediators of RD. Furthermore, by elucidating the molecular cargo contained within ocular EVs from pre-clinical RD disease models and plasma EVs of RD patients, we can uncover unifying molecular pathways driving disease, These can be developed as biomarkers of disease progression or therapeutic targets to preserve vision.
Specific Objectives:
i) Characterise the biological properties of retinal EVs in patients, and in human, murine and zebrafish models of RD.
ii) Elucidate the molecular constitution of these EVs to identify common and unique molecular factors within EVs that link to RD.
iii) Determine the sufficiency of pathology-related EVs/factors to mediate RD Impacts arising from this research include i) elucidating common roles of EVs in the pathobiology of RD, ii) Identification of therapeutic targets to preserve vision and iii) development of biomarkers to monitor disease progression or therapeutic response.
