Overview
Glaucoma is one of the UK’s most common causes of sight loss. In glaucoma, the nerve cells that connect the eye to the brain (together called the optic nerve) become damaged.
Previous animal studies have shown that the damage happens over a long period of time. First the optic nerve cells shrink and lose their connections from the light-sensitive part of the eye (the retina), and eventually they lose their connections to the brain.
Current treatments for glaucoma can help stop the condition from getting worse, but so far, none can give people back the sight they’ve already lost. But if the damage happens slowly it might be possible to revive cells before their connections are lost for good.
In this study the team wants to find out if human nerve cells follow the same pattern of damage. They will use high-powered 3D-imaging to look at nerve cells in donated eyes from people with and without glaucoma. They will also try to see how the stage of nerve damage relates to data from the donor’s previous sight tests.
Results from the project should tell us if, when and how human optic nerve cells lose their connections in glaucoma. We’ll also know more about what goes on inside the damaged nerve cells and whether they can still produce the energy they need to keep working.
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Scientific summary
Retinal ganglion cell degeneration in human glaucoma: a connectomic approach
While there have been advances in treatments that prevent progressive vision loss, we do not yet have interventions for the recovery of vision that has been lost. Work from animal models of glaucoma suggest that retinal ganglion cells (RGCs) undergo a prolonged period of degeneration, manifest as cell shrinkage and dendritic atrophy prior to loss of the axon. These cells therefore provide a valuable candidate population which could, if remodelled, provide a neural substrate for the recovery of vision in glaucoma.
In this study the research team is determining whether similar degenerative changes are seen in human glaucoma. They are using serial block face electron microscopy (SBF SEM) to image and then digitally reconstruct single RGCs in normal and glaucomatous human retinas. They will determine the extent to which RGCs in human glaucoma undergo degeneration, providing quantitative indices of dendritic integrity, synaptic density and underlying organelle disruption. As part of the project, they will define an informatic reconstruction pathway to provide the most efficient method for neuronal reconstruction in the human retina.
If they can demonstrate the presence of degenerating retinal ganglion cells, their data will provide strong support for the development of therapeutic interventions to harness the neuroplastic response of surviving cells for the recovery of vision in glaucoma. The technologies combined in this project also also have wide ranging application to the study of other retinal diseases.