2. Academic Validation
  3. SIRT3 mediates mitochondrial protection and attenuates mtROS-TXNIP-NLRP3 signaling activation in dry eye disease

SIRT3 mediates mitochondrial protection and attenuates mtROS-TXNIP-NLRP3 signaling activation in dry eye disease

  • Exp Eye Res. 2026 Jun:267:110960. doi: 10.1016/j.exer.2026.110960.
Di Zhang 1,  Yun He 2,  Fan Yang 3,  Yiran Chu 3,  Jiaxuan Jiang 3,  Boda Li 4,  Zeying Chen 5,  Qi Zhang 4,  Kai Hu 6
Affiliations

Affiliations

  • 1 Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, China; Department of Ophthalmology, West China Hospital, Sichuan University, Guoxue Xiang, No.37, Chengdu, China.
  • 2 Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, China; Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
  • 3 Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, China.
  • 4 Department of Ophthalmology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, 321 Zhongshan Road, Nanjing, China.
  • 5 Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, China; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, China.
  • 6 Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, China. Electronic address: [email protected].
PMID: 41791477 DOI: 10.1016/j.exer.2026.110960
Abstract

Background/aim: Dry eye disease (DED) is a chronic inflammatory disorder of the ocular surface in which mitochondrial dysfunction and oxidative stress have been increasingly implicated, yet the molecular mechanisms linking mitochondrial redox imbalance to inflammatory signaling remain unclear. This study aimed to investigate the role of Sirtuin 3 (SIRT3)-mediated mitochondrial protection in DED and to elucidate the involvement of the mtROS-TXNIP-NLRP3 signaling pathway.

Methods: We established animal model of benzalkonium chloride (BAC) induced mice, and cellular model of hypertonic medium-challenged human corneal epithelial cells (HCE-Ts). In these models, we evaluated the expression of proteins related to the TXNIP-NLRP3 pathway by Western blot. The mitochondrial function was assessed by detecting mtROS with fluorescence staining, measuring ATP production with chemiluminescence, detecting mitochondrial membrane potential with the JC-1 probe, and observing mitochondrial ultrastructure with transmission electron microscope. Changes in oxidative stress indicators were measured using a microplate reader.

Results: Our study found that TXNIP is a key link between mitochondrial redox imbalance and activation of the NLRP3 inflammasome pathway in HCE-Ts, giving the evidence of mtROS-TXNIP-NLRP3 pathway activation in DED. Overexpression of SIRT3 mitigated mitochondrial dysfunction and attenuated the downstream inflammatory pathway in the progression of DED. In vivo, the application of Honokiol (HKL, a reported SIRT3 Activator) eye drops, can improve mitochondrial function and attenuate the TXNIP-NLRP3 pathway in mice.

Conclusions: SIRT3 provided mitochondrial protection and attenuated the activation of mtROS-TXNIP-NLRP3 signaling in DED.

Keywords

Dry eye disease; Mitochondrial function; SIRT3; TXNIP.

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