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Exosomes as a therapy for glaucoma


   Cardiff School of Optometry & Vision Sciences

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  Dr B Mead, Prof M Votruba  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

This project is fully funded through the generosity of Glaucoma UK, including both tuition fees and £18,000 per year stipend

 

What we are looking for

We are seeking an individual who can demonstrate a passion for research, who has some laboratory experience and is keen to forge a career in the eye-research field.

The proposed research question

The principle aim of this project is to utilize small extracellular vesicles (sEV; including exosomes) from various sources and under different isolation techniques to promote survival of retinal ganglion cells (RGC), preserve their function, and prevent visual decline. In an effort to interrogate and exploit exosomes potential as a central nervous system (CNS) therapy for the eye, we will utilize state-of-the-art in vitro and in vivo models of glaucoma as well as human culture systems.

Background

Dysfunction and loss of retinal ganglion cells (RGC) is the leading cause of irreversible blindness and includes glaucoma as well as traumatic optic neuropathies. Glaucoma affects 80 million people (aged 40-80) with that number projected to increase to 120 million by 2040. The disease is characterised by the progressive loss of RGC, an irreplaceable central nervous system (CNS) neuron with the principal risk factor being an elevation in intraocular pressure (IOP). Currently, no neuroprotective treatment exists for glaucoma. The clinical importance of developing the first neuroprotective strategy for glaucoma is well understood, demonstrated by the number of on-going clinical trials.

Exosomes are small membranous packages released from every cell in the body, and contain an abundance of mRNA, miRNA and proteins that are delivered into recipient cells upon fusion with their membrane. Their contents vary depending on the cell source and while cancerous cells release exosomes that can propagate the disease, it can be hypothesised that adult stem cells, a cell type known for its role in regenerative medicine, releases exosomes that carry neuroprotective/pro-regenerative signals. Thus, exosomes are a novel communication method and a prime candidate as a treatment regime for injured CNS tissue. Our previous finding have demonstrated a therapeutic effect using bone marrow stem cell-derived exosomes, and this project will expand these findings, investigating new exosome therapies

 

Research Objectives

 

RO1 Quantification and characterisation (internal cargo/surface expression) of exosomes and their subtypes.

RO2 Therapeutic testing of different sources/subtypes/primed exosomes.

RO3 Testing of exosomes in a human in vitro model of retinal injury.

RO4 Determine mRNA/miRNA changes in RGC after injury and/or treatment

Techniques

·        Cell culture of rodent and human stem cells as well as primary retinal cells

·        Isolation of exosomes and characterization using NanoSight and Western Blot

·        Modelling glaucoma using in vitro and in vivo* models and delivering treatments using ocular injections

·        Therapeutic assessment of visual function using electroretinography, optical coherence tomography, and immunohistochemistry/microscopy

·        Embryonic stem cell culture and retinal differentiation.

 

This project offers the opportunity for the student to learn all of the above techniques, including in vivo techniques. They will work within the School of Optometry and have access to state-of-the-art facilities.

*This project utilizes animal models of glaucoma, a necessity when developing translatable therapies. Prospective students should be comfortable in using animal models.

Intellectual property developed from this project will belong to Cardiff University, a condition required by the funders.

Applicants should apply to the Doctor of Philosophy in Vision Sciences with a start date of 1st October 2022

In the research proposal section of your application, please specify the project title and supervisors of this project and copy the project description in the text box provided. In the funding section, please select the ‘self-funding’ option and specify the title of the studentship you are applying for. Please also include:

·                    an up-to-date CV

·                    a personal statement

·                    two references

Jan April

Year: 2022/23 

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