TABLE 2.

Strategies for glaucoma treatment involving autophagy.

Effect	Strategy	Experimental model	Molecular signaling pathway/autophagy markers	Effects of autophagy modulators	Ref
Autophagy induction	The neurosteroid AlloP	To generate an OH model, male SD rats were intracamerally injected with polystyrene microbeads	LC3B-II↑, SQSTM1↓	Prevented apoptosis and protected RGCs with autophagy activation	Ishikawa et al. (2021)
	Rapamycin	Male C57BL/6 J mice were subjected to acute HIOP (90–100 mmHg) for 60 min	mTOR inhibition	Prolonged autophagy activation and improved RGC survival	Russo et al. (2018)
	Tat-beclin 1 peptide or Torin 2	Tg-MYOCY437H mice	Mutant myocilin↓, LC3BII, ATG5, and beclin1↑, p62↓	Tat-beclin 1 peptide and Torin 2 significantly reduced IOP in Tg-MYOCY437H mice	Kasetti et al. (2021)
	Metformin	SD rats of GFS	AMPK/Nrf2 axis ↑, profibrogenic and inflammatory biomarkers↓	Protect against filtrating blebs scar formation in SD rats of GFS.	Li et al. (2020)
	Rapamycin	E50K-OPTN mice	LC3-II, p62↓, TDP-43 aggregation↓	Rapamycin reduce TDP-43 could suppress E50K-mediated apoptosis	Zhang et al. (2021b)
Autophagy inhibition	Blocker of lysosomal degradation (Baf-A1)	For COH, a dose of micromagnetic beads (2 μL) was injected into the anterior chamber of the right eye only once	Autolysosomes↑, p62↑	Biphasic autophagy in RGCs functioned dynamically during cell injury: promoting RGC apoptosis in the early stages (G4d) and resulting in RGC death in the second stage (G3w)	Zhang et al. (2020)
	Rac1 cKO	RGC Rac1 conditional knockout (Rac1 cKO) mice	mTOR↑, Beclin1, LC3, and Bak↓	Activated Rac1 exacerbated RGC injury in COH retinas, and Rac1 cKO significantly reduced apoptotic RGCs	Zhang et al. (2020)
	Overexpression of miR-708 and miR-335-3p	Chronic glaucoma mice were established by laser photocoagulation	ATG3↓, LC3II/I↓, P62↑	Overexpression of miR-708/miR-335-3p alleviated RGC apoptosis	Zhang et al. (2021a)
	Chloroquine	M98K-OPTN mice	TFRC↑	Chloroquine inhibited CASP3 and PARP1 cleavage, increase TFRC.	Sirohi et al. (2013)
	Ligustrazine (TMP)	A rat chronic hypertensive glaucoma model was induced by EVC.	p-PI3K, protein kinase B (p-Akt), and mTOR (p-mTOR)↑	Ligustrazine was neuroprotective in experimental glaucoma by inhibiting autophagy in RGCs	Du et al. (2021)

AlloP, allopregnanolone; SD, Sprague–Dawley; OH: ocular hypertension; LC3, light chain 3 protein; ATG, autophagy-related genes; GFS, glaucoma filtrating surgery; AMPK, AMP-activated protein kinase; Nrf2, nuclear factor erythroid 2-related factor 2; COH, chronic ocular hypertension; Rac1 cKO, Rac1 conditional knockout; OPTN, optineurin; PI3K, phosphatidylinositol 3-kinase; TFRC, transferrin receptor; EVC, episcleral vein cauterization; p-PI3K, phosphorylated.