How do support cells affect the optic nerve’s ability to regenerate?
- Type of funding: Early Career Investigator Award
- Grant Holder: Dr Barbara Lorber
- Institute: University of Cambridge
- Region: East of England
- Start date: January 2011
- End Date: March 2015
- Eye Category:
About 1 in 8 blind people are blind due to glaucoma – a group of conditions in which the cells the form the optic nerve die slowly over time. The optic nerve is the specialised cable that sends signals from the eye to the brain.
The most effective treatment for glaucoma is to reduce pressure in the eye, as high eye pressure is the main risk factor for the condition. But this doesn’t work for everyone and there is a great need for better treatments.
Recently, certain support cells in the light-sensitive part of the eye (the retina) have been found to help nerve cells in the retina to survive. They have helped regeneration in animals with glaucoma-like symptoms and other optic nerve damage. This is different to support cells in the optic nerve, which seem to prevent regeneration.In this project the team is aiming to find out whether transplanting retinal support cells can help nerve cell survival and re-growth. They are investigating ‘growth factors’ – substances produced by the support cells that help regeneration, and are also looking at whether it’s possible to make optic nerve support cells less able to prevent regeneration. The teams thinks that this 2-pronged approach could lead to new treatments for blindness in glaucoma and other conditions that affect the optic nerve.
Regenerating the optic nerve: how do glial cells modulate retinal ganglion cell axon growth and survival?Glaucoma, the second leading cause of blindness, is a neurodegenerative disease characterised by progressive death of retinal ganglion cells (RGC) and axon loss. Currently there are no therapies available to prevent RGC and axon loss other than reducing eye pressure, which is not effective in all patients. Therefore there is urgent need for the development of new treatment approaches.
Excitingly, activated retinal glia have recently been implicated as important positive mediators of RGC survival and axon regeneration in glaucoma and other optic nerve injury models. This is in contrast to activated glia in the optic nerve which are growth inhibitory. Indeed, limited retinal glia activation appears to compromise RGC survival and axon regeneration.
In the first part of the project the team is investigating whether transplantation of activated retinal glia can enhance RGC survival and axon regeneration. The second aim is to identify the protein/growth factor expression profile of activated retinal glia with the final aim to test the therapeutic potential of identified retinal glial-derived factors in mediating RGC survival and axon regeneration in glaucoma and optic nerve injury models. Furthermore, a combinatorial approach will be used to determine if a novel slow-release chondroitinase delivery system which degrades expression of inhibitory chondroitin sulfate proteoglycans in the glial scar can further enhance axon regeneration after optic nerve injury. The results generated by this study have the potential to lead to the development of new clinical therapies for glaucoma and acute optic nerve injury.
The team has shown that retinal support cells have the potential to help regeneration in glaucoma, optic nerve injury and spinal cord injury models.They have also shown that two types of retinal cells, retinal ganglion cells and retinal glial cells, can be successfully printed using a type of inkjet printer. This has the really exciting potential to mean that we could one day print a whole working retina in 3D using the right types of cells as a cure for some forms of blindness. The next step will be to find out how well this works with other types of cell – for example, the light-sensitive photoreceptors.
- Lorber, B., Hsiao, W.-K. & Martin, K. R. Three-dimensional printing of the retina. Current Opinion in Ophthalmology 27, 262–267 (2016).
- Lorber, B. et al. Retinal Glia Promote Dorsal Root Ganglion Axon Regeneration. PLoS ONE 10, e0115996 (2015).
- Johnson, T. V. et al. Identification of retinal ganglion cell neuroprotection conferred by platelet-derived growth factor through analysis of the mesenchymal stem cell secretome. Brain 137, 503–519 (2014).
- Lorber, B., Hsiao, W.-K., Hutchings, I. M. & Martin, K. R. Adult rat retinal ganglion cells and glia can be printed by piezoelectric inkjet printing. Biofabrication 6, 15001 (2014).
- Lorber, B., Guidi, A., Fawcett, J. W. & Martin, K. R. Activated retinal glia mediated axon regeneration in experimental glaucoma. Neurobiol. Dis. 45, 243–252 (2012).
- Lorber, B., Tassoni, A., Bull, N. D., Moschos, M. M. & Martin, K. R. Retinal ganglion cell survival and axon regeneration in WldS transgenic rats after optic nerve crush and lens injury. BMC Neurosci 13, 56 (2012).