Canagliflozin inhibits NLRP3 inflammasome activation to protect the retinal neurovascular unit in a mouse retinal vein occlusion model.

Abstract

To investigate whether Canagliflozin exerts a protective effect on the neurovascular units (NVUs) in a mouse retinal vein occlusion (RVO) model by inhibiting NLRP3 inflammasome activation, we establish a laser-induced RVO model in C57BL/6J mice and administer a Canagliflozin-containing diet. Retinal non-perfusion (RNP) formation is assessed via fundus fluorescein angiography (FFA). Retinal flat-mount immunofluorescence staining is used to detect microglial activation and retinal ganglion cells (RGCs) loss. Frozen-section immunofluorescence staining evaluates Müller glial cell activation, while TUNEL staining on frozen sections detects RGCs death. Western blotting is employed to analyze vascular leakage and NLRP3 inflammasome activation. Results demonstrated that Canagliflozin reduced RNP formation, inhibited albumin leakage, attenuated glial cells activation, mitigated RGCs loss, and suppressed NLRP3 inflammasome activation in RVO mice, independent of its hypoglycemic and weight-reducing effects. These findings suggested that Canagliflozin may protected the retinal NVUs in a mouse RVO model by inhibiting NLRP3 inflammasome activation.