Table 1.

Studies investigating pyroptosis in AMD.

Study	Model/Cell type studied	Technique	Findings	Relevance of findings to pyroptosis
Tarallo et al. (35)	Human RPE cells transfected with pAlu	MTS cell viability assay	The cytoprotective agent glycine (pyroptosis inhibitor) did not rescue Alu RNA-induced RPE degeneration	Alu RNA accumulation (a feature of GA) may not induce RPE degeneration via pyroptosis
Kerur et al. (36)	Human RPE cells transfected with pAlu, subretinal injection of pAlu in mice	Immunohistochemistry	Gsdmd−/− mice were resistant to Alu RNA-induced RPE degeneration; however, there was no observed cleavage of GSDMD into its N-terminal-pore-forming p30 fragment in pAlu-transfected human primary RPE cells or WT mice subretinally injected with Alu RNA	GSDMD is required for Alu RNA-induced RPE degeneration, but plays a non-pyroptotic role
Tseng et al. (37)	Lysosomal destabilization in ARPE-19 cells using Leu-Leu-OMe treatment	LDH release, caspase-1 inhibition with 10 μM Z-YVAD-FMK	Lysosomal destabilization induced LDH release from ARPE-19 cells, mediated by caspase-1	ARPE-19 cells undergo pyroptosis in response to lysosomal destabilization
Gao et al. (38)	Aβ intravitreal injections in Long-Evans rats	Western blotting	RPE-choroid protein lysates of rats receiving Aβ injections showed significantly greater cleavage of pro-GSDMD into GSDMD-N compared to controls	Aβ upregulates GSDMD-N, a driver of pyroptosis, in RPE cells
Sun et al. (39)	Aβ-treated ARPE-19 cells	Flow cytometry for positive PI and caspase-1 staining	Aβ significantly increased the proportion of ARPE-19 cells staining positive for both PI and caspase-1	Aβ induces pyroptosis in ARPE-19 cells
Yang et al. (40)	Aβ-treated ARPE-19 cells	Immunofluorescence, scanning electron microscopy	Aβ triggered increased levels of GSDMD-N, as well as swelling, bubbling, and cell membrane rupture in ARPE-19 cells	Aβ causes upregulation of a pyroptosis effector and morphological characteristics of pyroptosis in ARPE-19 cells
Liao et al. (41)	atRAL-treated ARPE-19 cells	Western blotting	Lysates of ARPE-19 cells treated with 15 uM atRAL showed increased levels of cleaved GSDME at 6 and 12 h but GSDMD remained full-length	atRAL-treated ARPE-19 cells may undergo GSDME-mediated, rather than GSDMD-mediated, pyroptosis

RPE, retinal pigment epithelium; pAlu, plasmid coding for Alu RNA; GA, geographic atrophy; WT, wild-type; ARPE-19, human adult retinal pigment; LDH, lactate dehydrogenase; Aβ, amyloid beta; PI, propidium iodide; GSDMD/E, gasdermin D/E; GSDMD-N, N-terminal of gasdermin D; atRAL, all-trans retinal.