Research grant awards worth £870K announced

Retina UK is delighted to announce that it has awarded three new research grants worth more than £870,000. The new projects will all explore innovative approaches to tackling inherited sight loss, forging a path towards treatment options for our community.

Dr Jörn Lakowski and Professor Andrew Lotery at Southampton University will investigate the preservation of central vision in retinitis pigmentosa (RP). Many of the genetic faults that cause RP only directly cause the degeneration of rod-shaped photoreceptors. These particular light-sensing cells are responsible for peripheral and low light vision, but have little to do with the central vision that allows us to read, watch TV, perform fine motor tasks and see detailed facial features; this is instead the job of cone-shaped photoreceptors. For this reason, central vision often remains intact in the early stages of RP as the cones are undamaged.

However, the cone photoreceptors do eventually suffer because they rely on nutritional support supplied by the rods, and this dwindles as more rods die. The mechanisms behind this survival signalling between rods and cones are poorly understood at an in-depth level. Dr Lakowski and Professor Lotery have used recent advances in genome engineering and stem cell technology to establish a novel human model system of RP by disabling a pivotal gene in the cone survival pathway. The new three year project will use this “mini retina” model to investigate the mechanism of RP-associated cone starvation and identify drugs that can prevent cone cell death, thereby protecting against the devastating end stages of central visual loss in a large proportion of RP cases.

Professor Jacqueline van der Spuy at UCL’s Institute of Ophthalmology will work with collaborators in Germany and Turkey to delve into the consequences of toxic accumulation of a molecule called cGMP. The three year project will use cell-based models of a very severe form of Leber congenital amaurosis (LCA) caused by mutations in the AIPL1 gene (LCA type 4), but cGMP accumulation also occurs in a number of other inherited retinal conditions, so understanding how it contributes to cell death could have much wider relevance.

The team will use cutting-edge techniques to follow up on clues about how excess cGMP impacts vital molecular pathways, with the aim of finding targets for therapeutic intervention. They also aim to test whether a particular potential drug can dampen cGMP’s toxic effects. The drug compound has already been extensively refined in other laboratory work, and Prof van der Spuy hopes that her project’s use of highly sophisticated disease models, based on human cells, would allow for rapid progress into clinical trials in LCA4, should the drug show promise.

Professor Jane Sowden, from University College London’s (UCL) Great Ormond Street Institute of Child Health, will be tackling the challenge of restoring some vision at the later stages of sight loss. At advanced stages of retinitis pigmentosa (RP) and other inherited retinal conditions, most of the light sensitive cells (photoreceptors) across the retina have died. A potential route to restoring vision is to generate new photoreceptors from stem cells and place these at the back of the eye.

To this end, Professor Sowden and her team will micro-engineer a photoreceptor cell patch to implant into the retina, creating a tiny millimetre dimension scaffold for the new cells to sit in. They are hopeful that this scaffold will aid the survival and organisation of the implanted photoreceptors. Over the course of the project, they aim to demonstrate that the patch can successfully be surgically implanted in an animal eye; they will assess its compatibility with the living tissues around it and evaluate the behaviour of the new photoreceptor cells. This is a first step towards development of a therapy for late-stage RP that could be helpful in a large proportion of cases, regardless of the underlying genetic fault.