Astrocyte Reactions to Optic Nerve Damage

The optic nerve is damaged in glaucoma which interrupts the communication of the eye with the brain. Non-neuronal (glial) cells in the optic nerve may be directly involved, either by harming the nerve fibers, or by protecting them. It is therefore important to understand the role of these cells in glaucoma more fully.

In glaucoma, ganglion cells – the only retinal neurons that send axons to the brain – are damaged and eventually degenerate, leading to vision loss. Recent research suggests that the first insult to ganglion cells happen at the junction where their axons leave the eye and form the optic nerve. In this place, supporting non-neuronal cells (astrocytes) closely contact the nerve fibers, and the behavior of these astrocytes is clearly altered in glaucoma. But are these changes helpful or harmful? The answer to this question will indicate whether inhibiting or stimulating astrocyte function is a viable therapeutic approach to prevent vision loss. We have proposed two specific aims: (1) it is important to better understand the function of optic nerve astrocytes, in particular their reactions to increased intraocular pressure and nerve damage. For this purpose, a mouse strain will be used that develops glaucoma and shows individual astrocytes with a brightly fluorescent label. This allows observing these cells directly at a level of detail that is not possible with more conventional staining techniques. (2) To answer the question whether astrocytes are helpful or harmful, it is important to know the timeline of events in the optic nerve. If astrocytes show signs of disease before the nerve fibers do, it would suggest that they are harmful. If it is the other way around, they are more likely to play a protective role.