2. Academic Validation
  3. The role of IGF2BP2 in macrophage-mediated NLRP3 inflammasome activation in the pathogenesis of dry AMD

The role of IGF2BP2 in macrophage-mediated NLRP3 inflammasome activation in the pathogenesis of dry AMD

  • Biol Direct. 2025 Apr 22;20(1):57. doi: 10.1186/s13062-025-00648-5.
Yuqing Zhao 1 2 3 4,  Yu Zhang 1 2 3 4,  Junfang Li 1 2 3 4,  Yifei Zhang 1 2 3 4,  Yi Qu 5 6 7 8
Affiliations

Affiliations

  • 1 Department of Geriatrics, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, China.
  • 2 Key Laboratory of Cardiovascular Proteomics of Shandong Province, Jinan, China.
  • 3 Jinan Clinical Research Center for Geriatric Medicine (202132001), Jinan, China.
  • 4 Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, China.
  • 5 Department of Geriatrics, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan, 250012, China. yiqucn@sdu.edu.cn.
  • 6 Key Laboratory of Cardiovascular Proteomics of Shandong Province, Jinan, China. yiqucn@sdu.edu.cn.
  • 7 Jinan Clinical Research Center for Geriatric Medicine (202132001), Jinan, China. yiqucn@sdu.edu.cn.
  • 8 Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, China. yiqucn@sdu.edu.cn.
PMID: 40264207 DOI: 10.1186/s13062-025-00648-5
Abstract

Background: Dry age-related macular degeneration (AMD) is a common chronic degenerative eye disease for which there is currently no effective treatment. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a recently identified m6A reader that binds RNA and maintains its stability, thereby participating in various biological processes. However, its role in dry AMD remains unclear.

Methods: In this study, we investigated the role of IGF2BP2 in macrophage NLRP3 inflammasomes using a sodium iodate-induced dry AMD model.

Results: Our results demonstrated that IGF2BP2 is highly expressed in the retinal-choroidal tissue induced by sodium iodate, with its effects primarily occurring in macrophages. The loss of IGF2BP2 ameliorating dry AMD. Mechanistically, methylated NLRP3 transcripts were subsequently directly recognized by the specific m 6 A "reader", IGF2BP2, to prevent NLRP3 mRNA degradation. Furthermore, in in vivo experiments, to maintain the eye's "immune privilege", we employed mesoporous silica-based cell therapy to target and regulate macrophage IGF2BP2, providing a foundation for the evaluation and translation of therapies targeting this gene.

Conclusion: our study reveals that the molecular mechanism of dry AMD pathogenesis involves IGF2BP2-mediated NLRP3 inflammasome activation in macrophages, highlighting IGF2BP2 as a promising biomarker and therapeutic target for dry AMD treatment.

Keywords

Dry Age-Related macular degeneration; IGF2BP2; M6A reader; Macrophages; NLRP3.

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