Human retinal organoids for modelling dry age-related macular degeneration and screening drugs

  • Genes Dis. 2025 Mar 7;12(6):101593. doi: 10.1016/j.gendis.2025.101593.
Xiaolu Hao  1  2 ,  Lu Du  1 ,  Guang Liu  3 ,  Zhaohui Li  1  2 ,  Shaojun Wang  1  2
Affiliations
  • 1. Senior Department of Ophthalmology, The Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
  • 2. Medical School of the Chinese PLA General Hospital, Beijing 100039, China.
  • 3. State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
PMID: 40837411 DOI: 10.1016/j.gendis.2025.101593
Abstract

Age-related macular degeneration (AMD) poses a significant threat to the vision of the elderly population globally. Unfortunately, there is no effective treatment available for dry AMD. In this study, we utilized human retinal organoids (ROs) stimulated with sodium iodate to establish a model for dry AMD. We assessed the Apoptosis of retinal Organoid cells and conducted RNA Sequencing to analyze molecular changes. Our findings indicate that metformin and the fetal Hemoglobin (HbF) inducer TN1 could protect ROs from sodium iodate induced damage and restore retinal function in murine model. The administration of metformin and TN1 alleviated Apoptosis in ROs and improved visual function. Studies of molecular mechanisms indicated that the protective effects of metformin and TN1 may be related to the HMOX1 gene, providing valuable insights for the development of new therapies for dry AMD via targeting HMOX1 and its downstream pathways.

Keywords
Dry age-related macular degeneration (AMD); Fetal hemoglobin inducer TN1; Metformin; Oxidative stress; Retinal organoid.
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