Overview
Proliferative vitreoretinopathy (PVR) is a condition that can develop after surgery to repair a detached retina. The retina is the light-sensitive layer that lines the back of the eye. If fluid from other parts of the eye leak underneath the retina through a hole or tear, the retina can pull away from the back wall.
PVR is the main reason why this surgery might fail. It can also lead to permanent sight loss. Drug treatment has the potential to prevent PVR. However the right drugs are not able to dissolve in silicone oil. This is a problem as silicone oil is often used to keep the retina in place while it heals. And if the drugs are injected they can build up around the silicone oil in a way that is toxic to the retina.
So in this project the research team is trying to transform the silicone oil plug so that it can also deliver retinoic acid as a drug. Retinoic acid is known to prevent cells from multiplying and so could help prevent PVR developing. The aim is to get the silicone oil plug to release retinoic acid in a slow and controlled way over a period of weeks. The team is testing to make sure that retinoic acid can’t reach toxic concentrations and to find out how well it prevents cells from multiplying. The results could lead to an effective way to prevent a sight-threatening complication from surgery for which there is currently no good treatment.
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Scientific summary
Development of a retinoic acid-silicone oil tamponade agent for treatment of proliferative vitreoretinopathy.
Proliferative vitreoretinopathy (PVR) correlates strongly with failure of retinal detachment surgery. Effective drug treatment may require exposure to an antiproliferative agent for several weeks. Silicone oil tamponades are used to flatten the retina following surgery. This project is developing a treatment strategy based on controlled release of a drug from a silicone oil tamponade. Retinoic acid (RA) is present naturally in the eye and has an antiproliferative effect on retinal pigment epithelial (RPE) cells in vivo. RA will be bound to functionalised silicone oil. Variation of silicone chain length will be used to control the release of therapeutically effective levels of RA into the aqueous. Unlike some other drug delivery methods, this approach will not lead to the release of unwanted toxic side-products. Sophisticated cell culture analysis techniques will be used to determine the efficacy of the RA in controlling PVR-like behaviour. The physical properties of the oil following modification will be tested in order to confirm that it remains an effective tamponade agent. The project will also develop a sophisticated in vitro model of the oil-filled eye, incorporating aqueous outflow, in order to investigate drug release and clearance from the eye. This model should reduce the need for animal studies and speed up translation of treatments from the lab to the clinic.