Related Experiment Video

Updated: Aug 6, 2026

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

Necroptosis Driven by JAK/STAT-RIPK-MLKL Signaling Mediates Corneal Epithelial Erosion

Hongyi Shen1,2, Jiayi Jin1, Jianqiang Zhang1,2

  • 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
|July 17, 2026
PubMed
Abstract

Insights

Interferon-gamma (IFN-γ) drives necroptosis, a form of cell death, in corneal erosion. Targeting this IFN-γ-necroptosis pathway offers a new therapeutic strategy for recurrent corneal erosion (RCE).

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Immunology

Background:

  • Recurrent corneal erosion (RCE) is an ocular surface disease characterized by poor epithelial-stromal adhesion and limited treatment options.
  • The precise mechanisms underlying RCE pathogenesis, particularly the role of programmed cell death, remain incompletely understood.

Purpose of the Study:

  • To investigate the role of necroptosis, a pro-inflammatory programmed cell death pathway, in the development of corneal erosion.
  • To explore the potential of targeting the IFN-γ-necroptosis axis as a therapeutic strategy for RCE.

Main Methods:

  • Established *in vitro* UVB injury models in human corneal epithelial cells (HCEpiCs) and *in vivo* UVB-induced corneal erosion models in mice.
  • Utilized LC-MS/MS proteomics, pathway enrichment analysis, immunofluorescence, qRT-PCR, and Western blotting to examine cellular signaling and molecular pathways.
  • Administered topical anti-IFN-γ antibody treatment in the *in vivo* model to assess therapeutic efficacy.

Main Results:

  • UVB exposure significantly increased necroptosis-related proteins, IFN-γ signaling, JAK/STAT activation, and RIPK1/RIPK3/MLKL expression and activation in corneal epithelium.
  • Necroptosis correlated with increased damage-associated molecular pattern (DAMP) release, NLRP3 inflammasome activation, and IL-1β maturation.
  • *In vivo* anti-IFN-γ treatment improved corneal epithelial integrity, enhanced epithelial-stromal attachment, and reduced necroptosis and inflammasome activation markers.

Conclusions:

  • A novel pathogenic axis involving IFN-γ signaling driving a necroptotic-inflammatory loop was identified in corneal erosion.
  • The findings provide a new molecular understanding of corneal epithelial injury and highlight the IFN-γ-necroptosis axis as a promising therapeutic target for RCE.
Keywords:
JAK/STAT pathwayNLRP3 inflammasomeRIPK-MLKL pathwayinterferon-gamma (IFN-γ)necroptosisrecurrent corneal erosion (RCE)

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