Additional Table 6.

Effects of intermittent fasting and sleep on glymphatic/neurological activity and the visual system

Lifestyle component	Exp. Type	Model/Species	Exp. Protocols	Main findings	Citation
Intermittent Fasting	in vivo	APP/PS1 mice	° IF group fed every other day, fasted the following day for 5 mon ° Assessed via Morris water maze test, immunohistochemistry, histology	↓ Cognitive dysfunction, prevented brain from increase of Aβ deposition, and restored the AQP4 polarity to localize in astrocytic endfeet ↓ Expressions of AQP4-M1 and HDAC3, and ratio of AQP4-M1/M23 ratio in cerebral cortex	Zhang et al. (2017)
	in vitro	Human U251 glioma cells	° Cells cultured for 3 h with βOHB, βOHB + Aβ, Aβ only, or medium only ° After 3 h, cells with Aβ further treated with Aβ25−35 for 12 h ° Various DNA and protein expression	↓ Expressions of AQP4-M1 and HDAC3, AQP4-M1/M23 ratio by βOHB ↑ Expressions of AQP4-M23 and miR-130a via HDAC3 expression inhibition
	in vivo	Humans	° 27 healthy adults fasting during month of Ramadan ° Full ophthalmic exam and OCTA done at AM and PM of wk 2 and 3 of Ramadan, and 2 mon later	↓ Lower IOP, CCT, and average RNFL thickness during evening of fasting ↑ Whole and peripapillary RPC density and ONH vCDR during fasting	Nilforushan et al. (2020)
Sleep	in vivo	C57BL/6J mice	° 3 groups: naturally asleep to awake, awake to ketamine/xylazine anesthesia, awake to norepinephrine receptor antagonists ° CSF tracer infusion via cisterna magna ° Visualized CSF tracer influx via in vivo two-photon imaging	↑ 60% of interstitial space in naturally asleep and anesthetic mice ↓ ~95% of influx in periarterial and parenchymal spaces of awake mice ° Sleeping and anesthetized mice showed influx of CSF tracers in periarterial spaces, subpial regions, brain parenchyma ° Aβ cleared 2× faster in sleeping/anesthetized mice than in awake mice ↑ Cortical interstitial volume when adrenergic receptors are inhibited	Xie et al. (2013)
	in vivo	Humans	° Glaucoma and healthy participants ° Assessed via sleep survey, retinal photos, 2 VF tests per eye	° Suggest that worse sleep parameters may be risk factor/consequence of glaucoma ° Lowest disc defined glaucoma and/or VFD prevalence associated with 7 h/night ° Highest disc defined glaucoma associated with ≥ 10 h/night ° Highest VFDs associated with ≤ 3 h and ≥ 10 h/night ° Association between disc defined glaucoma and ≤ 9 min and ≥ 30 min sleep latency ↑ VFD ∝ likely to not perform optimally in daytime ° No association found between glaucoma and any sleep disorders	Qiu et al. (2019)

Aβ: Amyloid-beta, AQP4: aquaporin-4, BDNF: brain-derived neurotrophic factor, βOHB: β-hydroxybutyrate, CCT: central corneal thickness, CSF: cerebrospinal fluid, HDAC3: histone deacetylase 3, IF: intermittent fasting, IOP: intraocular pressure, OCTA: optical coherence tomography angiography, ONH: optic nerve head, POAG: primary open angle glaucoma, RNFL: retinal nerve fiber layer, RPC: radial peripapillary capillary, vCDR: vertical cup/disc ratio, VF: visual field, VFD: visual field defects.