2. Academic Validation
  3. MSC-Derived Exosomal lnc-AGT-3: A Novel Anti-Angiogenic Target in Age-Related Macular Degeneration Through p53 Signaling Pathway

MSC-Derived Exosomal lnc-AGT-3: A Novel Anti-Angiogenic Target in Age-Related Macular Degeneration Through p53 Signaling Pathway

  • Aging Cell. 2026 Feb;25(2):e70377. doi: 10.1111/acel.70377.
Lingjie Kong 1 2 3,  Xiaoyan Han 1 2 3,  Siyi Qi 1 2 3,  Duo Li 4,  Jingyue Zhang 4,  Linyu Zhang 4,  Shujie Zhang 1 2 3,  Qin Jiang 4,  Biao Yan 5,  Chen Zhao 1 2 3 6
Affiliations

Affiliations

  • 1 Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.
  • 2 Key Laboratory of Myopia and Related Eye Diseases, NHC; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China.
  • 3 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China.
  • 4 The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.
  • 5 Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 6 Xiamen Eye Center of Xiamen University, Xiamen, China.
PMID: 41524223 DOI: 10.1111/acel.70377
Abstract

Neovascular age-related macular degeneration (nAMD) is a major cause of irreversible vision impairment in elderly populations, characterized by pathological angiogenesis beneath the macula. Although anti-VEGF therapies have demonstrated clinical effectiveness, significant challenges including drug resistance and the need for frequent intravitreal injections persist. As natural nanovesicles, exosomes derived from mesenchymal stem cell (MSC) can mediate intercellular communication, making them an attractive alternative for modulating cellular processes. This study explored the anti-angiogenic effects of MSC-derived exosomes in nAMD, with particular emphasis on the role of a specific exosomal lncRNA lnc-AGT-3. Our results showed that lnc-AGT-3 expression was reduced in both nAMD patients and choroidal neovascularization (CNV) models, and its overexpression effectively inhibited pathological angiogenesis in vitro and in vivo. Mechanistically, lnc-AGT-3 enhanced the p53 signaling pathway by blocking the ubiquitination and degradation of p53 and ultimately inhibited neovascularization, a process potentially linked to its direct interaction with heterogeneous nuclear ribonucleoprotein K (hnRNP K). Our findings position MSC-derived exosomes enriched with lnc-AGT-3 as an innovative therapeutic paradigm for nAMD, acting through p53 pathway modulation to potentially overcome current treatment limitations.

Keywords

lnc‐AGT‐3; MSC‐exosomes; angiogenesis; hnRNP K; neovascular AMD; p53 signaling pathway.

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