Role of Intracranial Hypotension on Optic Neuropathy

The proposed study will develop an animal model of decreased intracranial pressure and examine whether the lowering of intracranial pressure has a role in the development of glaucoma-like changes in the optic nerve and retinal ganglion cells.

Glaucoma is a combination of diseases that affect the optic nerve, the connection between the eye and the brain that enables us to see. Primary open angle glaucoma (POAG) is the most common form of glaucoma, generally associated with high intraocular pressure. The importance of intraocular pressure on optic nerve health has been studied extensively. In contrast, the role of intracranial pressure, the opposing force to intraocular pressure acting on the optic nerve has not been studied in detail. For over 80 years medical doctors and research scientists have debated whether or not intracranial pressure contributes to the development of glaucoma. Recent studies have identified an important correlation: Individuals with POAG tend to have a decreased intracranial pressure when compared to normal age-matched controls. However, the role of intracranial hypotension has not been studied in relation to POAG, mainly because there are no models to study decreased intracranial pressure. To study the role of intracranial hypotension, we are developing a rat model of intracranial hypotension and examining whether decreasing intracranial pressure will result in glaucoma-like changes in the optic nerve and retina. Our proposal will 1) develop a rodent model of intracranial hypotension where the pressure will be monitored continuously in real-time; 2) test whether decreasing intracranial pressure affects optic nerve and retinal health; and 3) analyze the relationship between intracranial pressure and intraocular pressure within the same animal. This innovative approach will enable us to control changes in intracranial pressure and observe the associated changes within the eye. Completion of this project will help to answer the question of whether or not intracranial pressure contributes to the development of glaucoma.