Glaucoma patients suffer from a high prevalence of sleep disorders, yet the underlying mechanism at play remains unclear. Intrinsically photosensitive retinal ganglion cells, which are involved in circadian rhythms and known to be injured in glaucoma, may play a role. A team presenting at the ARVO 2021 virtual meeting this week suggested that sleep-regulating systems that involve the ventrolateral preoptic nucleus (VLPO)—a major subcortical structure that induces sleep by producing inhibitory signals—are indeed impaired in glaucoma.

The study assessed 52 glaucoma patients and 26 healthy subjects. The researchers paid particular attention to the VLPO and the arousal systems, including the posterior hypothalamus, dorsal raphe, median raphe, locus coeruleus and habenula and cortical networks.

At the subcortical level, the investigators observed enhanced functional connectivity between the VLPO and posterior hypothalamus, and between the habenula and median raphe in the glaucoma patients. At the cortical level, they noted reduced functional connectivity between VLPO and the medial and posterior occipital cortices. The occipital cortex of glaucoma patients also presented reduced amounts of gamma-aminobutyric acid but not glutamate, resulting in increased excitatory and inhibitory balance.

“Our study shows that the sleep-regulating subcortical systems involving VLPO and their projections to the occipital cortex are impaired under glaucoma,” the study authors concluded. “Such alterations may underlie the high occurrence of sleep disorders in glaucoma.”