Human retinal organoids functionally bridge a transected optic nerve in a rat model

  • Cell Stem Cell. 2026 Jul 2;33(7):1161-1173.e7. doi: 10.1016/j.stem.2026.04.020.
Yu Gong  1 ,  Huiyu Zhu  2 ,  Lingling Ge  2 ,  Luoyan Wan  3 ,  Simin Huang  4 ,  Zhining Su  5 ,  Mosaab Mohamed Elmahdi  6 ,  Zhuang Xiong  4 ,  Mingxia Ji  2 ,  Qingqing Gou  2 ,  Weihua Yu  7 ,  Jiawen Li  8
Affiliations
  • 1. Department of Ophthalmology, University-Town Hospital, Chongqing Medical University, Chongqing 401331, P.R. China. Electronic address: [email protected].
  • 2. Department of Ophthalmology, University-Town Hospital, Chongqing Medical University, Chongqing 401331, P.R. China.
  • 3. The Second Clinical College, Chongqing Medical University, Chongqing 401331, P.R. China.
  • 4. The Fifth Clinical College, Chongqing Medical University, Chongqing 401331, P.R. China.
  • 5. The First Clinical College, Chongqing Medical University, Chongqing 401331, P.R. China.
  • 6. The International Education College, Chongqing Medical University, Chongqing 401331, P.R. China.
  • 7. Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, P.R. China. Electronic address: [email protected].
  • 8. Department of Ophthalmology, University-Town Hospital, Chongqing Medical University, Chongqing 401331, P.R. China. Electronic address: [email protected].
PMID: 42184825 DOI: 10.1016/j.stem.2026.04.020
Abstract

Functional restoration of vision in adult mammals remains unattainable following complete transection of the optic nerve. In this study, we address this challenge by heterotopically transplanting human retinal organoids into the transection cavity of the optic nerve in adult rats. One month after transplantation, treated Animals exhibited partial recovery of visual function, including a direct pupillary light reflex, visually evoked electrophysiological responses, and visually guided behaviors, which were sustained for at least 3 months. Neuroanatomical tracing and three-dimensional imaging revealed the formation of a structured host-graft coupling spanning the transection gap. Functional engagement of the graft was further supported by chemogenetic inhibition, which led to coordinated attenuation of visual function. Together, these findings provide proof of concept that heterotopic retinal Organoid transplantation can establish a relay-like pathway supporting partial functional signal transmission across a completely transected optic nerve, offering an alternative conceptual framework for repairing severe optic nerve injuries.

Keywords
heterotopic transplantation; human retinal organoids; optic nerve injury and repair; visual function restoration.
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