Sleep deprivation disrupts the lacrimal system and induces dry eye disease

Abstract

Sleep deficiency is a common public health problem associated with many diseases, such as obesity and cardiovascular disease. In this study, we established a sleep deprivation (SD) mouse model using a ‘stick over water’ method and observed the effect of sleep deficiency on ocular surface health. We found that SD decreased aqueous tear secretion; increased corneal epithelial cell defects, corneal sensitivity, and apoptosis; and induced squamous metaplasia of the corneal epithelium. These pathological changes mimic the typical features of dry eye. However, there was no obvious corneal inflammation and conjunctival goblet cell change after SD for 10 days. Meanwhile, lacrimal gland hypertrophy along with abnormal lipid metabolites, secretory proteins and free amino-acid profiles became apparent as the SD duration increased. Furthermore, the ocular surface changes induced by SD for 10 days were largely reversed after 14 days of rest. We conclude that SD compromises lacrimal system function and induces dry eye. These findings will benefit the clinical diagnosis and treatment of sleep-disorder-related ocular surface diseases.

N-Palmitoylethanolamine Maintains Local Lipid Homeostasis to Relieve Sleep Deprivation–Induced Dry Eye Syndrome

“…In this study, we used an SD mouse model to mimic the DED induced by sleep deficiency. A previous study found that the pathological changes affecting SDE mice include decreased aqueous tear secretion, defects and squamous metaplasia of corneal epithelial cells, and corneal barrier function damage (Li et al, 2018). We did not find obvious corneal inflammation after 10 days of SD.…”

“…The periodic acid-Schiff staining results indicated that SD slightly increased the mean number of goblet cells, compared with control group (101 ± 7 vs. 90 ± 25), but the difference was not statistically significant ( Figures 8A, B). This change in goblet cells is an adaptive response to the decreased tear secretion at the early stage of DED (Li et al, 2018). Application of PEA markedly increased conjunctival goblet cell density (144 ± 29) ( Figure 8C).…”

“…Before using in the experiment, all mice adapted to the environment for a week, and were examined to ensure ocular surface health. SD was performed using a "stick over water" method in a standard laboratory setting, as previously described (Li et al, 2018). Two mice were housed per cage in standard laboratory conditions.…”

“…Corneal epithelial damage is a significant DED-associated change. SD mice have signs of ocular surface damage that is similar, to some extent, to DED (Li et al, 2018). Corneal epithelial permeability was assessed via an ocular surface fluorescence staining test using the 70 kD high-molecularweight fluorescent molecule, OGD.…”

“…The results indicated that a higher dry eye prevalence was present in groups with severe short sleep duration (< 4 h). Our preliminary studies using mouse models found that sleep deprivation (SD) causes ocular surface disorders, including aqueous tear deficiency, corneal epithelial defects, corneal sensitivity, and apoptosis (Li et al, 2018). Hypertrophy and increased lipid accumulation are compensatory LG responses.…”