The roles of mitochondrial dynamics and NLRP3 inflammasomes in the pathogenesis of retinal light damage

Abstract

With the widespread popularity of electronic products and the diversification of lighting equipment, ocular photochemical damage caused by light has attracted research attention. Although such equipment mainly cause damage to the retina, the specific pathogenesis has not been systematically elucidated. Thus, the goal of this study was to explore the relationship between mitochondrial dysfunction and the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in retinal cell death caused by light damage. We used a white light-emitting diode source to establish a mouse model of retinal light damage and observed significant changes of retinal structure and an impairment of visual function. Further experiments revealed that dynamin-related protein 1 (Drp1)-mediated excessive mitochondrial fission induced overproduction of reactive oxygen species in the retinal cells, leading to apoptosis, activation of microglia, and formation of the NLRP3 inflammasome. This, in turn, triggered a series of inflammatory cascade reactions, leading to pyroptosis. We also carried out red light and Drp1 inhibitor treatment and found that retinal damage and the decline in visual function caused by white light could be partially ameliorated. In conclusion, this study clarified the association between mitochondrial dynamics and the NLRP3 inflammasome in retinal light damage and provides opportunities for therapeutic intervention.

Dynamin-Related Protein 1 Is Involved in Mitochondrial Damage, Defective Mitophagy, and NLRP3 Inflammasome Activation Induced by MSU Crystals

“…The LCM imaging revealed that the enhanced mitochondrial aspect ratio in MSU crystal-treated BMDMs was also largely reversed by Drp1 knockdown ( Figure 2(b) ). Since the excessive mitochondrial fission mediated by Drp1 could exacerbate the production of mitochondrial ROS [ 28 ], we also observed that Drp1 knockdown significantly decreased mitochondrial ROS and total intracellular ROS generation in MSU crystal-treated BMDMs (Figures 2(c) and 2(d) ). We sought to explore whether Drp1 knockdown mediated antioxidant protein expression induced by MSU crystals.…”

“…Mito/autophagy is also involved in MSU crystal-induced NLRP3 inflammasome activation or IL-1 β release [ 54 ]. Drp1-mediated excessive mitochondrial fission can promote the activation of the NLRP3 inflammasome [ 28 ]. However, the role of Drp1 signaling on NLRP3 inflammasome activation induced by MSU crystals is ambiguous.…”

Modified Linggui Zhugan Decoction protects against ventricular remodeling through ameliorating mitochondrial damage in post-myocardial infarction rats

“…Mitochondrial dysfunction is deemed a precursor to cell death ( 79 ), and the core reason for heart failure progression ( 6 ). Among the many mechanisms that influence mitochondrial stability, mitochondrial dynamics is crucial to cell quality control and function ( 80 , 81 ) and its disturbance is one cause of apoptosis ( 82 ). For instance, mitochondrial fusion promotes structural and functional stability of the inner membrane, thus protecting cells from apoptosis, while fission is related to cell apoptosis ( 36 ).…”

HSPB8 Overexpression Ameliorates Cognitive Impairment in Diabetic Mice via Inhibiting NLRP3 Inflammation Activation

“…NLRP3 inflammasome activation was also observed in diabetic cognitive impairment model mice/rats [ 34 , 35 ]. Mitochondrial fission was reported to regulate NLRP3 inflammasome activation [ 36 – 38 ]. Further experiments in vitro revealed that when the ratio of p-Drp1S616/DRP1 was upregulation, the activation of NLRP3 inflammasomes, including NLRP3, cle-caspase-1, and IL-1 β was increased.…”