Association Between Glaucoma and Sleep Disorders

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.

Glaucoma patients have a high incidence of sleep disorders. This relationship implies that glaucomatous pathogenesis may involve alterations in sleep-regulating systems. Here, we will examine how glaucoma affects the sleep-regulating subcortical systems. In particular, we focus on the ventrolateral preoptic nucleus (VLPO), a major sleep-inducing hub in human subcortical structures. VLPO has been thought of as an ‘off’ switch that induces sleep by inhibiting the subcortical arousal systems and the cortex. Critically, VLPO receives input from intrinsically photosensitive retinal ganglion cells (ipRGCs), which are known to be damaged in glaucoma. Thus, it is reasonable to suggest that the loss of ipRGCs may result in impaired function of VLPO in glaucoma. In this BrightFocus project, we test the hypothesis that the sleep-regulating subcortical systems involving VLPO and their inhibitory projections to the cortex are impaired in glaucoma. We will use multimodal brain neuroimaging, clinical ophthalmic assessments, and sleep quality assessments in early-stage and advanced-stage glaucoma patients, and healthy subjects. The outcomes should provide a mechanistic account of the high incidence of sleep disorders in glaucoma and could lead to therapeutic advancements benefitting millions of people.

Glaucoma patients have a high incidence of sleep disorders. While the ventrolateral preoptic nucleus, the main sleep-inducing hub receives the input from intrinsically photosensitive retinal ganglion cells, that are known to be impaired in glaucoma, no studies have yet examined how the sleep-regulating systems are affected by glaucoma. This proposal will provide a mechanistic account of glaucoma pathogenesis that underlies sleep disorders. Particularly, this study will reveal if alterations in the functional connectivity and neurochemical balance underlies sleep disorders in glaucoma.

The outcomes of this project will provide a better understanding of glaucoma pathogenesis that underlies sleep disorders. Furthermore, the outcomes will advance clinical treatments for glaucoma patients who suffer from sleep disorders.