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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Novel developments in retinal regeneration: Advances and future outlooks in stem cell therapy
Marco Zeppieri, Federico Visalli, Mutali Musa, Alessandro Avitabile, Rosa Giglio, Daniele Tognetto, Caterina Gagliano, Fabiana D’Esposito, Francesco Cappellani
Marco Zeppieri, Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
Marco Zeppieri, Rosa Giglio, Daniele Tognetto, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste 34129, Italy
Federico Visalli, Department of Ophthalmology, University of Catania, Catania 95123, Italy
Mutali Musa, Department of Optometry, University of Benin, Benin 300283, Nigeria
Alessandro Avitabile, Faculty of Medicine, University of Catania, Catania 95123, Italy
Caterina Gagliano, Fabiana D’Esposito, Francesco Cappellani, Department of Medicine and Surgery, University of Enna “Kore”, Enna 94100, Italy
Caterina Gagliano, Francesco Cappellani, Eye Center, G.B. Morgagni-DSV, Catania 95100, Italy
Fabiana D’Esposito, Imperial College Ophthalmic Research Group Unit, Imperial College, London NW1 5QH, United Kingdom
Co-corresponding authors: Marco Zeppieri and Caterina Gagliano.
Author contributions: Zeppieri M, Visalli F, Musa M, Avitabile A, Giglio R, Tognetto D, Gagliano C, D’Esposito F, and Cappellani F wrote the outline, assisted in the writing of the draft and final paper, and assisted in the editing, making critical revisions of the manuscript and viewing all versions of the manuscript; Zeppieri M, Visalli F, Musa M, Avitabile A, and Cappellani F did the research and writing of the manuscript; Zeppieri M, Gagliano C, D’Esposito F, and Cappellani F were responsible for the conception and design of the study; Zeppieri M, Visalli F, Musa M, Gagliano C, D’Esposito F, and Cappellani F contributed to the scientific editing. All authors provided the final approval of the article. Zeppieri M and Gagliano C contributed equally to this manuscript as co-corresponding authors.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Marco Zeppieri, MD, PhD, Department of Ophthalmology, University Hospital of Udine, p. le S. Maria della Misericordia 15, Udine 33100, Italy.
mark.zeppieri@asufc.sanita.fvg.it
Received: July 1, 2025
Revised: August 3, 2025
Accepted: November 11, 2025
Published online: December 26, 2025
Processing time: 180 Days and 10.2 Hours
Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, and Stargardt disease, are primary contributors to irreversible vision loss globally. Due to the scarcity of effective curative treatments, stem cell therapy has emerged as a revolutionary advancement in ophthalmology. In the last ten years, significant advancements have been achieved in the derivation of retinal pigment epithelium and photoreceptor precursors from human embryonic stem cells and induced pluripotent stem cells, with initial clinical trials indicating safety and potential efficacy. Innovative delivery platforms, such as biodegradable scaffolds, microcarrier suspensions, and minimally invasive subretinal devices, are tackling prior challenges related to cell survival and integration. Simultaneously, gene-edited and patient-specific induced pluripotent stem cells are positioned to surmount immunological and ethical constraints. Future combinatorial strategies that incorporate stem cells with gene therapy, CRISPR-mediated editing, and bioengineered retinal organoids offer potential for personalized and regenerative methodologies. Nonetheless, enduring functional integration, immune tolerance, and oncogenic safety continue to pose significant challenges. To effectively transition from laboratory research to clinical application, collaborative frameworks among academic institutions, biotechnology companies, and regulatory agencies will be crucial for unlocking the complete therapeutic potential of stem cell-based treatments for retinal diseases. Stem cell therapy has transitioned from a distant promise to an advancing reality set to transform retinal care.
Core Tip: Stem cell therapies have a revolutionary potential to restore eyesight in individuals afflicted with retinal degenerative disorders, including age-related macular degeneration, retinitis pigmentosa, and Stargardt disease. Progress in human embryonic stem cell- and induced pluripotent stem cell-derived retinal cells, novel delivery mechanisms, and gene-editing methods is expediting clinical use. Nonetheless, enduring functional integration, immunological tolerance, and carcinogenic hazards persist as unresolved difficulties. Future success will rely on combinatorial strategies and global regulatory alignment to fully realize the potential of regenerative ophthalmology.
