Mapping Scleral Fibroblasts and Their Significance in Glaucoma

The goal of this project is to learn more about the processes that control eye remodeling in glaucoma in order to discovery new glaucoma treatments. The outer wall of the eye – the sclera – remodels in glaucoma, and this process influences how eye pressure affects the optic nerve. Cells within the sclera regulate this remodeling process and can either protect the nerve or make it more susceptible to damage. In the first aim , we will map how the architecture of these cells changes in the early and late stages of glaucoma. We hypothesize that increased eye pressure will disrupt cellular architecture. In the second aim, we will screen for compounds that restore normal cellular function and protect the nerve from pressure damage.

Permanent vision loss from glaucoma is caused by damage to nerve cells that occurs at the optic nerve head – the opening through which the nerve first exits the eye. Damage to these cells occurs because pressure within the eye pinches the nerve at the optic nerve head. Intraocular pressure reduction alleviates this pinching and allows the cell to function properly. An alternate approach to glaucoma treatment is altering the behavior of the wall of the eye that surrounds the optic nerve head so the nerve is no longer pinched regardless of the eye’s pressure. We previously showed this approach protects nerve cells and identified a promising lead drug. Thus, this proposal aims to understand better how the wall of the eye remodels in glaucoma and test an approach to prevent nerve cell death by altering this process.

Most neuroprotective approaches target nerve cells within the eye or their support system within the eye. Our approach is innovative as it targets cells involved in remodeling the eye in order to form a protective barrier around the optic nerve.

Gaining a better understanding of the cellular processes that underlie scleral remodeling in glaucoma will improve our understanding of a fundamental – and little explored – process in glaucoma and identify potential therapeutic approaches to better treat glaucoma.