2. Academic Validation
  3. Transcription factor EGR2 drives cataract formation through IGFBP3-mediated oxidative injury in lens epithelial cells

Transcription factor EGR2 drives cataract formation through IGFBP3-mediated oxidative injury in lens epithelial cells

  • Free Radic Biol Med. 2025 Oct 13:241:773-788. doi: 10.1016/j.freeradbiomed.2025.10.009.
Wanqian Li 1,  Yue Zou 1,  Wanqiu Zheng 1,  Jiaojiao Zhang 2,  Chao Cen 1,  Ruonan Li 1,  Hong Cheng 1,  Shengping Hou 3,  Wenjuan Wan 1,  Liang Liang 4,  Juan Kang 4,  Shijie Zheng 5,  Ke Hu 6
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Prevention and Treatment on Major Blinding Diseases, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, 400016, China.
  • 2 The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Prevention and Treatment on Major Blinding Diseases, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, 400016, China; The People's Hospital of Yubei District of Chongqing city, Chongqing, 401120, China.
  • 3 Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
  • 4 People's Hospital of Qamdo, Qamdo, 854000, China.
  • 5 The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Prevention and Treatment on Major Blinding Diseases, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, 400016, China. Electronic address: zhengshijie0824@126.com.
  • 6 The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Prevention and Treatment on Major Blinding Diseases, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, 400016, China; People's Hospital of Qamdo, Qamdo, 854000, China. Electronic address: cqhuke@hospital.cqmu.edu.cn.
PMID: 41093149 DOI: 10.1016/j.freeradbiomed.2025.10.009
Abstract

Cataracts, a prevalent ocular disorder, represent the leading cause of global blindness. Evidence indicates that oxidative stress-induced lens epithelial cells (LECs) Apoptosis constitutes a key pathogenic mechanism in age-related cataract (ARC). Although the transcription factor EGR2 has been recognized as both a novel senescence regulator and a critical mediator in ophthalmic diseases including uveitis and diabetic retinopathy, its precise role in cataract remains undefined. In this study, EGR2 was identified via transcriptome Sequencing as a potential core regulator of cataract development. Subsequent investigations demonstrated elevated EGR2 expression in the anterior capsule from cataract patients, oxidatively damaged LECs, and a sodium selenite-induced rat cataract model. Functional studies revealed that EGR2 overexpression exacerbated oxidative stress and promoted Apoptosis in LECs. Notably, intravitreal administration of AAV-shEGR2 significantly attenuated lens opacification. RNA-seq and CUT& Tag findings indicated that EGR2 directly bound to its downstream target insulin-like growth factor binding protein 3 (IGFBP3). Furthermore, IGFBP3 silencing effectively reversed EGR2-mediated oxidative injury and Apoptosis in LECs, while administration of recombinant IGFBP3 protein accelerated cataract progression in vivo. This study delineates EGR2 as a pivotal regulator in cataract pathogenesis, proposing a novel therapeutic target while uncovering the molecular mechanism of oxidative stress-mediated lens pathology.

Keywords

Apoptosis; Cataract; EGR2; IGFBP3; Oxidative stress.

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