Abstract
Purpose :
Glaucoma patients present a high prevalence of sleep disorders, yet its underlying mechanisms remain unclear. Intrinsically photosensitive retinal ganglion cells (ipRGCs), which are involved in circadian rhythms are also known to be injured in glaucoma. The ipRGCs provide input to the ventrolateral preoptic nucleus (VLPO), a major sleep-inducing subcortical structure. VLPO induces sleep by delivering inhibitory signals to the subcortical arousal systems and the cortex. In the current study, we investigated whether the sleep-regulating subcortical systems involving VLPO and their inhibitory projections to the cortex are impaired in glaucoma.
Methods :
37 glaucoma patients and 22 healthy subjects underwent 3T anatomical MRI and resting-state functional MRI (fMRI) with eyes closed. Additionally, 15 glaucoma patients and 4 healthy subjects were scanned for 3T anatomical MRI and proton magnetic resonance spectroscopy (MRS). For MRS, we recorded gamm-aminobutyric acid (GABA), glutamate and N-acetyl-aspartate (NAA) signals from the same single voxel (2.2×2.2×2.2 cm3) placed in the occipital cortex (Figure 2A).
We analyzed the fMRI data using CONN. Brain regions-of-interest included VLPO, a main sleep-promoting area, and the arousal systems including posterior hypothalamus (PH), dorsal raphe (DR), median raphe (MR), locus coeruleus (LC), and habenula and cortical networks. We fitted glutamate and GABA separately using LCModel. The amount of GABA and glutamate were normalized by NAA values. The excitatory and inhibitory balance (E/I balance) was calculated by dividing the amount of glutamate by that of GABA.
Results :
At the subcortical level, enhanced functional connectivity (FC) was observed between VLPO and PH, a main arousal structure (P=0.048; Figure 1A,B,D), and between habenula and MR (P=0.006; Figure 1A,C,E) in glaucoma patients. At the cortical level, reduced FC was observed between VLPO and the medial occipital cortex (P=0.014; Figure 1F,G,H) and the posterior occipital cortex (P=0.006; Figure 1F,G,I). The occipital cortex of glaucoma patients also presented reduced amount of GABA (P=0.001; Figure 2C) but not glutamate (P=0.486; Figure 2D), resulting in increased E/I balance (P=0.048; Figure 2B).
Conclusions :
Our study shows that the sleep-regulating subcortical systems involving VLPO and their projections to the occipital cortex are impaired under glaucoma. Such alterations may underlie the high occurence of sleep disorders in glaucoma.
This is a 2021 ARVO Annual Meeting abstract.