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Our proposed study will examine the aqueous humor, the fluid in the front of the eye, of patients who are undergoing eye surgery. We will measure both a byproduct (hydrogen peroxide) and a protectant (ascorbic acid) of oxidative damage, as well as oxygen levels in different parts of the front of the eye. By aiding in further understanding of this oxidative mechanism of glaucoma damage, it may lead to innovative therapies for this devastating condition.

We aim to understand the mechanisms of neurodegeneration in glaucoma that may lead to sleep disorders. 1. We will investigate whether the altered functional connectivity in the sleep-inducing area and the arousal systems in the subcortical brain structures underlie sleep disorders in glaucoma. 2. We will test whether the altered functional connectivity between the main sleep-inducing subcortical area and the cortical areas underlies sleep disorders in glaucoma. 3. We will test whether the altered neurochemical balance between excitation and inhibition in the main sleep-inducing area and cortical areas underlies sleep disorders in glaucoma.

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.

Astrocytes are known to play vital roles in the maintenance of retinal ganglion cells, with these interactions adversely affected in glaucoma. In particular, as is common across a number of neurodegenerative diseases, the mitochondria of these cells are damaged, presumably leading to the disease phenotypes. The use of human pluripotent stem cells allows for the precise modeling of these interactions in a dish, providing the spatial and temporal resolution to closely examine how mitochondrial function is changed in these cells as a result of glaucoma, as well as how these changes in mitochondria alter the health and function of the cells as a whole.

In the present application, we hypothesize that responses retinal astroglial cells are directly responsible for glaucoma-induced optic nerve damage and retinal ganglion cell death by producing neurotoxic agents, triggering inflammation, and generating an inhospitable environment.