Protective Effect of Necrosulfonamide on Retinal Injury in Acute Glaucoma Rats through Alleviating Pyroptosis

Abstract

Background: Pyroptosis has been proved to play a role in vision impairment of acute glaucoma, a type of optic neuropathy caused by an abrupt increase in intraocular pressure, leading to irreversible visual loss. The objective of this study was to probe into the protective effect of pyroptosis inhibitor necrosulfonamide (NSA) on vision loss in acute glaucoma and its potential mechanism. Methods: An acute glaucoma model in rats was established by anterior chamber perfusion. The expression of pyroptosis proteins was estimated through western blot and quantified real-time polymerase chain reaction (qRT-PCR), while the interleukin (IL)-1β and IL-18 levels in retinal vitreous tissues were determined using enzyme-linked immunosorbent assay (ELISA). The retinal tissues were examined by electron microscopy, and performed immunofluorescence staining. The rats were given different doses of NSA, and the visual function was assessed by flash visual evoked potentials and full field electroretinogram analysis. The retinal structure was evaluated by optical coherence tomography peripapillary analysis and hematoxylin and eosin (H&E) staining. In vitro, Müller cells were modeled by oxygen-glucose deprivation/reperfusion (OGD/R) and treated with NSA. The effects of NSA on cell proliferation and pyroptosis-related proteins were evaluated using cell counting kit-8 (CCK-8) assay, qRT-PCR, and western blot. Results: After modeling, the acute glaucoma rats significantly increased the key proteins and inflammatory factors associated with pyroptosis (p < 0.05) and typical features of pyroptosis were observed. NSA treatment alleviated visual impairment and improved retinal damage in rats with acute glaucoma, and reduced the expression of IL-1β and IL-18 by inhibiting gasdermin-D (GSDMD). In the OGD/R model of Müller cells, the cell proliferation was inhibited, and the expressions of NOD-like receptor family pyrin domain containing 3 (NLRP3), absent in melanoma 2 (AIM2) inflammasome, Cleaved-GSDMD, IL-1β, and IL-18 were upregulated, while NSA increased cell proliferation and inhibited pyroptosis. Conclusions: Pyroptosis was involved in the pathogenesis of acute glaucoma in rats, and NSA can protect visual function by inhibiting pyroptosis. Therefore, NSA has great potential in treating acute glaucoma.