Additional Table 2.

Summary of various agents on GABA activity and associated neurological changes related to the visual system

Compounds/Agents of interest	Type of study	Exp. Method(s)	Model/Species/Culture	Exp. Protocols	Relevant findings	Citation
DAMGO, DPDPE	Animal	in vivo	New Zealand white rabbits	° 2 μmol/μL or 4 μmol/μL into ARC or SC ° IOP before and every 5 min for 1 h after injection	↓ IOP post-ARC injection of μ/δ agonists ↓ IOP post-ARC and SC injection of naloxone but not in conjunction with μ/δ agonist injections	Jin et al. (2014)
GABA	Animal	in vivo	C57BL/6J, AQP4−/− mice	° Dissolved in CSF tracer ° Via cisterna magna	° GABA promotes glymphatic drainage in wild-type but not AQP4-/-mice ° No effects on paravascular movement	Wu et al. (2020)
		in vivo	Wistar rats	° 1 g/kg IP ° 32.5 min or 62.5 min before sacrifice	↓ GABA steady state concentrations and accumulation in post-3 wk IOP increase group	Moreno et al. (2008)
		in vivo, histochemistry	DBA/2J and C57BL/6J mice, Sprague Dawley rats	° IHC or IF staining to visualize GABA receptor expression in ARC	↑ Expression of GABA receptor in ARC in high IOP rat and DBA/2J mice models ↓ IOP and GABA receptor expression in high IOP models with GABA antagonists	Gong et al. (2018)
GABA, butanoate	Genomic	PARIS	-	° 3108 POAG cases and 3430 controls total	° Specific genes of the butanoate metabolism pathway found to contribute to GABA metabolism ° Suggests association with glaucoma pathogenesis	Bailey et al. (2014)
PNU-282987 ((α7- nAChR) agonist)	Animal	in vivo	Wistar rats	° 5 μL of 100 μM IV ° IOP elevation by EVC	↑ GAD65/67 levels ↑ Presynaptic release of GABA onto RGCs	Zhou et al. (2017)
-	Case studies		Humans	° 10-d stress reducing and residual vision activating treatments	↑ Humphrey VF test scores post-10 day treatment	Sabel et al. (2018)
-	Animal	in vitro, histochemistry	Sprague-Dawley rats	° Rats sacrificed 60 d post- RYGB ° LCM, RNA sequencing, IHC staining	° Aqp4 gene among most down-regulated genes after RYGB ° Suggests gliosis reversal and decrease in glia cell function	Barkholt et al. (2019)

ARC: Arcuate nucleus; α7-nAChR: alpha7 nicotinic acetylcholine; CSF: cerebrospinal fluid; DAMGO: [D-Ala², N-Me-Phe⁴, Gly⁵-ol]-enkephalin; DPDPE: [D-Pen²,D-Pen⁵]- enkephalin; EVC: external jugular vein; GABA: gamma-aminobutyric acid; IF: immunofluorescence; IHC: immunohistochemical; IOP: intraocular pressure; IP: intraperitoneal; IV: intravitreal; LCM: laser capture microdissection; PARIS: pathway analysis by randomization incorporating structure; POAG: primary open-angle glaucoma; RGC: retinal ganglion cells; RYGB: Roux-en-Y gastric bypass; SC: subconjunctival.