Professor Keith Martin (University of Cambridge) is investigating the manipulation of P13K signalling to enhance regeneration of retinal ganglion cells.

The optic nerve is like an electrical cable that carries visual signals from the eye to the brain. It is made up of nerve fibres, called axons, which arise from retinal ganglion cells (RGCs) in the retina. Once damaged, the connection between the eye and brain is lost. As axons cannot regrow any deficit in visual ability is permanent and may leave the patient blind.

The research focuses on regenerating damaged axons in the optic nerve with the ambition of re-establishing visual connections to the brain and ultimately restoring sight.

In recent years, it has been demonstrated the RGCs can be stimulated to regenerate their axons following optic nerve injury. This has been achieved by manipulating molecules that control the process of cell growth.  Manipulation of these molecules trigger a series of chemical reactions, known as a signalling cascade, that triggers growth programs within the cell and subsequently axon regrowth. One signalling cascade that is known to promote axon regeneration is the AktmTOR pathway. Researchers have activated this pathway by genetically deleting a gene called PTEN that functions to dampen activation of the Akt/mTOR pathway.

Although the effect of PTEN gene deletion on axon regeneration is well documented, it seems likely that far greater numbers of regenerating axons will be required to have a meaningful impact on visual function.  The effect of PTEN gene deletion on axon regeneration is limited by the abundance of the signalling receptor that acts as the initial activator for this pathway, which is not very abundant in RGCs.

The main aim of the research is to enhance activation of the Akt/mTOR pathway using an alternative approach and increase the number of regenerating axons.  It is hoped to achieve this by stimulating P13K activity directly, in combination with PTEN gene deletion.