Related Experiment Video
Updated: Aug 15, 2025
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
GSDMD deficiency ameliorates hyperoxia-induced BPD and ROP in neonatal mice
Sarah Sonny1, Huijun Yuan1, Shaoyi Chen1
1Neonatology and Batchelor Children Research Institute, University of Miami Miller School of Medicine, 1580 NW 10thAve, Miami, FL, 33136, USA.
Insights
Gasdermin D (GSDMD) plays a key role in hyperoxia-induced bronchopulmonary dysplasia and retinopathy of prematurity in premature infants. Targeting GSDMD may offer new treatments for these conditions.
Area of Science:
- Neonatal Medicine
- Inflammation and Immunology
- Developmental Biology
Background:
- Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are significant complications in premature infants treated with oxygen.
- A mechanistic link between hyperoxia, BPD, and ROP is not fully understood.
- Gasdermin D (GSDMD) is a critical mediator of pyroptosis and inflammation.
Purpose of the Study:
- To investigate the role of GSDMD in the pathogenesis of hyperoxia-induced BPD and ROP.
- To define the mechanistic pathways involving GSDMD in these conditions.
Main Methods:
- Utilized global GSDMD knockout (GSDMD-KO) mouse models.
- Exposed mice to hyperoxia to induce BPD and ROP.
- Performed histological, molecular, and RNA sequencing analyses on lung and retinal tissues.
Main Results:
- GSDMD-KO significantly protected against hyperoxia-induced BPD and ROP.
- GSDMD deficiency reduced inflammation, cell death, and improved tissue development in lungs and retinas.
- Shared inflammatory and developmental pathways were identified in both conditions and modulated by GSDMD-KO.
Conclusions:
- GSDMD is crucial in the development of hyperoxia-induced BPD and ROP.
- Targeting GSDMD presents a potential therapeutic strategy for preventing and treating BPD and ROP in premature infants.
Abstract:
Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are among the most common morbidities affecting extremely premature infants who receive oxygen therapy. Many clinical studies indicate that BPD is associated with advanced ROP. However, the mechanistic link between hyperoxia, BPD, and ROP remains to be explored. Gasdermin D (GSDMD) is a key executor of inflammasome-induced pyroptosis and inflammation. Inhibition of GSDMD has been shown to attenuate hyperoxia-induced BPD and brain injury in neonatal mice. The objective of this study was to further define the mechanistic roles of GSDMD in the pathogenesis of hyperoxia-induced BPD and ROP in mouse models. Here we show that global GSDMD knockout (GSDMD-KO) protects against hyperoxia-induced BPD by reducing macrophage infiltration, improving alveolarization and vascular development, and decreasing cell death. In addition, GSDMD deficiency prevented hyperoxia-induced ROP by reducing vasoobliteration and neovascularization, improving thinning of multiple retinal tissue layers, and decreasing microglial activation. RNA sequencing analyses of lungs and retinas showed that similar genes, including those from inflammatory, cell death, tissue remodeling, and tissue and vascular developmental signaling pathways, were induced by hyperoxia and impacted by GSDMD-KO in both models. These data highlight the importance of GSDMD in the pathogenesis of BPD and ROP and suggest that targeting GSDMD may be beneficial in preventing and treating BPD and ROP in premature infants.
