Table 2 Effects of FDA-approved autophagy-target drugs on retinal degenerative diseases

Chloroquine (CQ) & hydroxychloroquine (HCQ)

Autophagy inhibition to Autophagosome & Lysosome

Harmful

Glaucoma

Treatment of CQ and HCQ causes RGC and retinal damage

[244,245,246]

Diabetic retinopathy

CQ worsens the progression of diabetic retinopathy

[248]

Blindness

Rheumatic patients treated with HCQ leads to blindness

[247]

Rapamycin

Autophagy activation by mTORC1 inhibition

Protective

Glaucoma

Rapamycin is neuroprotective in a chronic hypertensive glaucoma model and increases RGC survival following optic nerve transection

[142, 224]

AMD

Rapamycin prevents AMD-related aging of RPE cells

[222]

Diabetic retinopathy

Rapamycin ameliorates the high glucose-induced ROC in the RPE

[223]

Optic neuropathy

Rapamycin-induced autophagy results in less damage from G11778A mutation, the most common cause of Leber’s hereditary optic neuropathy

[225]

Everolimus

Autophagy activation by mTORC1 inhibition

Protective

Glaucoma

Everolimus suppresses the scar formation in glaucoma filtering surgery in an animal model

[226]

AMD

Everolimus suppresses angiogenesis molecular pathways in the onset of wet AMD

[228]

Diabetic retinopathy

Everolimus suppresses angiogenesis molecular pathways in the onset of diabetic retinopathy

[229]

Harmful

Optic neuropathy

Long-term administration of everolimus may cause reversible encephalopathy syndrome and bilateral optic neuropathy after kidney transplantation

[231, 232]

Temsirolimus

Autophagy activation by mTORC1 inhibition

Protective

AMD

Temsirolimus inhibits RPE and endothelial cell proliferation and decreases VEGF and PDGF expression

[233]

Diabetic retinopathy

Temsirolimus is considered as an antiangiogenic drug for diabetic retinopathy progression

[234]

Metformin

Autophagy activation by AMPK activation and subsequent inhibition of mTORC1 signaling

Protective

Glaucoma

Metformin is used to control blood sugar and is considered to reduce the risk of the onset of glaucoma, AMD, and diabetic retinopathy in diabetic patients

[236,237,238]

AMD

Diabetic retinopathy

Lithium (LiCl)

Autophagy activation by mTOR-independent pathway

Protective

Glaucoma

In animal studies, LiCl was reported as an autophagy inducer, which could alleviate the progression of glaucoma, diabetic retinopathy, and optic neuropathy

[240,241,242]

Diabetic retinopathy

Optic neuropathy

Ripasudil

Autophagy activation by inhibition of rho-associated coiled-coil containing protein kinase 1 (ROCK1)

Protective

Glaucoma

Ripasudil is the key component in ophthalmic solutions for treating glaucoma by reducing IOP

Ripasudil promotes axonal protection in an animal model

[220, 221]

Steroids

Autophagy activation by GABA_A receptor

Protective

Retinal degeneration

Neurosteroids induces the autophagy pathway to protect retinal neurons

[218]

Inhibiting autophagosome biogenesis pathway

Harmful

Glaucoma

Steroid therapy in the eye leads to the dysregulation of TMCs and develop glaucoma pathology

[219]