Table 2.
Summary of the potential agents of pyroptosis in ocular diseases
| Disease | Agent | Target | Pathway | Promote (+)/suppress (−) ODs | Animal/cell model | References | Research in other fields |
|---|---|---|---|---|---|---|---|
| Diabetic retinopathy | Vitamin D3 | ROS | ROS/TXNIP/NLRP3 | − | Patient vitreous sample/human retinal microvascular endothelial cells | [109, 246] |
Acute kidney injury/human tubular epithelial cell [247] Hepatic injury [248] |
| Ghrelin | ROS | ROS/NLRP3 | − | ARPE-19/Wistar rats | [115] |
Nonalcoholic fatty liver disease [249] Multiple sclerosis/neuroinflammation [250] Traumatic brain injury-induced acute lung injury [251] |
|
| Hydrogen sulfide (H2S) | ROS | ROS/NLRP3 | − | ARPE-19 | [114] |
Ischemia–reperfusion (I/R)-induced acute kidney injury [252] |
|
| MCC950 | NLRP3 | TXNIP/Nek7-NLRP3/caspase-1/GSDMD | − | Retinal microglia, C57BL/6J mice, human retinal endothelial cells | [98, 100, 255] | Aβ accumulation [256] | |
| β-Hydroxybutyrate | NLRP3 | ER stress/NLRP3 | − | C57BL/6J mice | [229] | Renal ischemia/reperfusion injury [233] | |
| Methylene blue (MB) | NLRP3 | NLRP3/caspase-1 | − | Sprague–Dawley rats | [230] | Myelodysplasia [234] | |
| Z-YVAD-FMK | caspase-1 | Caspase-1/IL-1β | − | Retinal microglia | [98] |
Lung inflammation [257] Neuroblastoma [258] |
|
| H3 relaxin | P2X7R | P2X7R/NLRP3 | − | Human retinal microvascular endothelial cells | [102] | Nephrocalcinosis [259] | |
| METTL3 | miR-25-3p | miR-25-3p/PTEN/Akt | − | ARPE-19 | [13] |
Diabetic kidney disease [260] Liver fibrosis (+) [261] |
|
| lncRNA MIAT | miR-342-3p | miR-342-3p/caspase-1 | + | Human retinal pericyte | [107] | Diabetic cardiomyopathy [262] | |
| Age-related macular degeneration | A740003 (P2X7 receptor antagonist) | P2X7R | P2X7R/ROS/NLRP3 | − |
ARPE-19 cells C57BL/6 mice |
[124] | Osteoarthritis [232] |
| miR‐22‐3p | NLRP3 | NLRP3/caspase-1 | − | ARPE‐19/Balb/c mice | [133] | Cerebral ischemia/reperfusion injury [263] | |
| INF39 | NLRP3 | NLRP3/caspase-1 | − | ARPE‐19 | [126] |
Liver injury [264] Mycoplasma pneumoniae infection [265] |
|
| Tranilast | NLRP3 | NLRP3/caspase-1 | − | ARPE‐19 | [227] | Atherosclerosis [266] | |
| Lycium barbarum polysaccharides (LBP) | amyloid β1-40 (Aβ1-40) | Aβ1-40/NLRP3/caspase-1/GSDMD | − | ARPE-19 | [10] | – | |
| Baicalin | miR-223 | miR-223/NLRP3/caspase-1 | − | ARPE-19 | [127] | Hepatic injury in non-alcoholic steatohepatitis [267] | |
| Glaucoma | Melatonin | NF-κB | NF-κB/NLRP3/caspase-1/GSDMD | − | Sprague–Dawley rats/ganglion cell | [223] |
Atherosclerosis [268] Hepatic ischemia/reperfusion injury [269] Cerebral ischemia [270] Diabetes-induced brain injury [271] |
| Kaempferol | NF-κB | NF-κB/NLRP3/caspase-1 | − | Retinal ischemia–reperfusion (I/R) mice model | [62] |
Spinal cord injury [235] Parkinson’s disease [236] |
|
| Dry eye disease | Calcitriol | NLRP3 | NLRP3/caspase-1/GSDMD | − | Human corneal epithelial cells | [177, 272] | – |
| Disulfiram | GSDMD | GSDMD | − | Human corneal epithelial cells | [177] |
Severe acute pancreatitis [273] Lipopolysaccharide-induced sepsis/ulcerative colitis [274] |
|
| Keratitis | Wedelolactone | IKK | Caspase-4/5/11/GSDMD | − | Human corneal keratocytes | [181] | Acute pancreatitis [245] |
| Disulfiram | GSDMD | GSDMD | − | Neutrophil and macrophage | [241] |
Severe acute pancreatitis [273] Lipopolysaccharide-induced sepsis/ulcerative colitis [274] |
|
| Diabetic corneal endothelial keratopathy | lncRNA KCNQ1OT1 | miR-214 | miR-214/caspase-1 | + | Corneal endothelial | [188] |
Diabetic cardiomyopathy [275] Diabetic nephropathy [276] |
| Uveitis | Anakinra | IL-1β | IL-1β/IL-1R | − | Patients with Behçet’s disease | [277] |
Atherosclerosis [278] Muscle inflammation [279] Acute liver failure [280] |
| Canakinumab | IL-1β | IL-1β/IL-1R | − | Patients with Behçet’s disease | [277, 281] | Myocardial infarction [282] | |
| Minocycline | TLR4 | TLR4/IL-1β | − | Rat endotoxin-induced uveitis model | [283] |
Depression [284] Spinal cord injury [285] |
MIAT myocardial infarction associated transcript, ROS reactive oxygen species, NLRP NOD-like receptor protein, GSDMD gasdermin D, IKK inhibitor of nuclear factor kappa-B kinase, TXNIP thioredoxin interacting protein, PTEN phosphatase and tensin homolog, ARPE-19 adult retinal pigment epithelial cell line-19, IL-1R interleukin-1 receptor, ODs ocular diseases