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

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.