Repairing the retina’s blood supply before sight-threatening damage occurs
Research details
- Type of funding: Project Grant
- Grant Holder: Dr David Simpson
- Institute: Queen’s University Belfast
- Region: Northern Ireland
- Start date: December 2013
- End Date: February 2017
- Priority: Treatment
- Eye Category:
Overview
When the blood supply to the light-sensitive layer of the eye (the retina) is damaged it can lead to new blood vessels growing that are leaky and unhealthy. They’re behind the sight loss in conditions such as retinopathy of prematurity and diabetic retinopathy. Treatment with drugs known as anti-VEGFs can stop the new growth, but may have serious side effects in the long term.In this project the team is taking a different approach and looking to repair the damaged blood supply before the point when new blood vessels would start growing. Research has shown that certain stem cells naturally release little packets (called vesicles) into the blood. The vesicles contain substances that can help control blood vessel growth.
They are studying mice with oxygen-damaged retinas to find out what happens when these vesicles are injected into the blood. They are also engineering the vesicles’ contents to see if they can improve the ability to trigger blood vessel repair and working out how to direct the vesicles to the places they are most needed.
If it works it could lead to a potential treatment that’s easier to develop than one that’s based on whole stem cells. And this type of treatment could be given earlier than current anti-VEGFs, before sight is badly under threat.
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Scientific summary
Vesicular delivery of microRNAs to enhance regeneration of ischaemic retina
Background: Improved therapies for ischaemic retinopathies are required to replace repeated anti-VEGF treatments, which have potential long term side-effects. Vascular stem/progenitor cell-based therapies offer an attractive alternative approach to address the underlying pathology and promote revascularisation of the ischaemic retina rather than directly blocking the subsequent neovascularisation. These cells release extracellular vesicles (EVs) which have been shown to modulate angiogenesis. The EVs mediate paracrine effects upon target cells, at least in part, by transfer of small regulatory ‘microRNAs’.
Aim: The aim of the project is to test a strategy designed to harness the EVs released from endothelial progenitor cells (EPCs) to promote vascular regeneration.
Methods: EPCs will be cultured from blood and EVs isolated by ultracentrifugation. The activity of the EVs will be assessed in in vitro models of angiogenesis and in a mouse model of oxygen-induced retinopathy. The EVs will be manipulated to try and enhance their ability to promote revascularisation. They will be engineered to carry specific microRNAs known to modulate angiogenesis and peptides designed to enhance their targeting towards the endothelium will be expressed on the EV surface.
Anticipated outcomes: Demonstration that EVs from EPCs can enhance reparative retinal angiogenesis in an animal model and optimisation of the delivery, microRNA content and target cells. A potential novel therapy for ischaemic retinopathies, without the inherent complications of cell transplantation. Successful EV-mediated delivery of microRNAs to specific cells would have huge implications because of its potential to facilitate therapeutic RNAi in other diseases.
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Research update
So far the team has learned more about the size and content of the vesicles. They have also found that when the vesicles are injected into the eye, they hook up with blood vessels and start having a significant effect on new growth.