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.