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.
We have previously demonstrated that adult stem cells are efficacious in a variety of CNS injury models including glaucoma. Following further study, we identified small extracellular vesicles (sEV) including exosomes as a key mediator in this paracrine-mediated neuroprotection/axonal regeneration. 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.
In this project you will isolate exosomes from multiple human stem cell types, characterize them using NanoSight and Western blot, and deliver them into in vitro and in vivo models of retinal disease. Firstly, rodent retinae are dissected, cultured, and treated with exosomes, with cell numbers and neurite regeneration analysed using immunohistochemistry and microscopy. A similar model is utilized with human retina, generated via the differentiation of human embryonic stem cells into retinal tissue. Finally, exosome treatments are also administered into rodent models of glaucoma induced through the injection of microbeads into the anterior chamber. Therapeutic efficacy is confirmed using electroretinography, optical coherence tomography and immunohistochemistry.
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.
Applicants should apply to the Doctor of Philosophy in Vision Sciences with a start date of 1st October 2021.
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
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