Table 2.
Studies investigating pyroptosis in DR.
Study | Model/Cell type studied | Technique | Findings | Relevance of findings to pyroptosis |
---|---|---|---|---|
Jiang et al. (42) | Primary human RECs incubated in 25 mM high glucose | Western blotting | Increased protein levels of NLRP3, cleaved caspase-1, and IL-1β in high glucose vs. normal glucose group | The NLRP3/caspase-1-mediated pyroptotic pathway may be activated in HRMECs in response to high glucose |
Chen et al. (43) | HRMECs incubated in 30 mM high glucose | Western blotting | Increased protein levels of NLRP3, cleaved caspase-1, and IL-1β in high glucose vs. normal glucose group | The NLRP3/caspase-1-mediated pathway may be activated in RECs in response to high glucose |
Gu et al. (44) | HRMECs incubated in 30 mM high glucose | PI and caspase-1 FLICA staining, flow cytometry | Pyroptosis and caspase-1 activity were markedly increased in high-glucose-treated HRMECs vs. the control group | High glucose promotes pyroptotic cell death in HRMECs |
Gan et al. (45) | HRPs incubated in 30 mM high glucose | Pore formation: PI uptake Cell lysis: LDH release Cytokine release: ELISA |
High glucose-treated HRPs experienced greater pore-formation, cell lysis, and release of IL-1β and IL-18 compared to controls → these effects were reversed with NLRP3, caspase-1, or GSDMD inhibition | High glucose can induce the loss of HRPs via GSDMD-mediated pyroptosis |
Yu et al. (46) | HRPs incubated in 200 μg/ml AGE-BSA | Protein expression: Western blotting Cytokine release: ELISA LDH activity: LDH assay kit Cell viability: cell counting kits |
AGE-BSA increased expression of active caspase-1 and GSDMD-N and promoted secretion of IL-1β, IL-18, and LDH in HRPs, alongside decreasing HRP viability | HRPs undergo GSDMD-mediated pyroptosis when treated with AGE-BSA |
Du et al. (47) | Mouse primary retinal Müller cells incubated in 30 mM high glucose | Western blotting | Increased levels of NLRP3, cleaved caspase-1, and IL-1β in high glucose-treated mouse retinal Müller cells | The NLRP3/caspase-1-mediated pyroptotic pathway may be activated in Müller cells cultured under high glucose conditions |
Xi et al. (48) | ARPE-19 cells incubated in 50 mM high glucose | Western blotting | High glucose upregulated protein expression of caspase-1, GSDMD, NLRP3, IL-1β, and IL-18 in ARPE-19 cells | High glucose may promote GSDMD-mediated pyroptosis in ARPE-19 cells |
Zha et al. (49) | ARPE-19 cells incubated in 50 mM high glucose | Western blotting | High glucose upregulated protein expression of caspase-1, GSDMD, NLRP3, IL-1β, and IL-18 in ARPE-19 cells | High glucose may promote GSDMD-mediated pyroptosis in ARPE-19 cells |
HRMECs, human retinal microvascular endothelial cells; RECs, retinal endothelial cells; PI, propidium iodide; FLICA, fluorochrome-labeled inhibitors of caspases; HRPs, human retinal pericytes; LDH, lactate dehydrogenase; ELISA, enzyme-liked immunosorbent assay; AGE-BSA, advanced glycation end-product modified bovine serum albumin; ARPE-19, human adult retinal pigment epithelial cell line-19; NLRP3, nucleotide-binding and oligomerization domain (NOD)-like receptor family pyrin domain-containing 3; IL-1β; interleukin-1β; IL-18, interleukin-18; GSDMD, gasdermin D; GSDMD-N, N-terminal of gasdermin D.