From Engraftment to Vision: Defining Evidence of Functional Success in Retinal Cell Replacement Therapy
5 affiliations
- 1Division of Ophthalmology and Visual Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK
- 2First Department of Ophthalmology, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
- 3Vantage Biosciences Ltd., London SW1Y 5ES, UK
- 4Department of Ophthalmology, University Hospital of Basel, 4031 Basel, Switzerland
- 5Ophthalmology Unit, Department of Neuroscience, University of Padua, 35122 Padua, Italy
Abstract
Retinal graft survival and post-treatment visual improvement do not, alone or together, demonstrate functional cell replacement. Apparent benefit may reflect material transfer, trophic rescue, residual host function or procedural and measurement effects. This critical narrative review uses a structured PubMed search covering January 2020 to August 2026, supplemented by seminal studies, to assess retinal pigment epithelium (RPE), photoreceptor, retinal sheet or organoid, and retinal ganglion cell (RGC) transplantation. We separate mechanistic attainment, downstream outcomes and claim-specific causal confidence. Authentic RPE replacement requires donor epithelial function across the host interface, without new synapses. Photoreceptor replacement requires donor phototransduction and transmission to host retinal circuitry; composite grafts additionally require identification of the active donor components. RGC replacement requires both retinal afferent integration and functional reconnection with appropriate central targets. Selected photoreceptor studies demonstrate persuasive local physiological coupling, but durability, donor necessity and generalisability remain incompletely established. Human evidence principally supports feasibility, safety and graft-associated anatomy, rather than convincingly donor-mediated visual restoration. We propose a non-linear evidence framework in which outcomes cannot substitute for secure donor provenance, cell-specific function or host–graft coupling. Spatial concordance, durability, controls, disease-model relevance and experimental unit should qualify every claim.
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BibTeX
@article{panos2026from,
title = {{From Engraftment to Vision: Defining Evidence of Functional Success in Retinal Cell Replacement Therapy}},
author = {Georgios D. Panos and Theo Empeslidis and Eleftherios Chatzimichail and Lorenzo Motta and Zisis Gatzioufas and Winfried Amoaku},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15201840},
url = {https://www.mdpi.com/2073-4409/15/20/1840},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - From Engraftment to Vision: Defining Evidence of Functional Success in Retinal Cell Replacement Therapy
AU - Georgios D. Panos
AU - Theo Empeslidis
AU - Eleftherios Chatzimichail
AU - Lorenzo Motta
AU - Zisis Gatzioufas
AU - Winfried Amoaku
PY - 2026
DA - 2026/10/10
JO - Cells
DO - 10.3390/cells15201840
UR - https://www.mdpi.com/2073-4409/15/20/1840
AB - Retinal graft survival and post-treatment visual improvement do not, alone or together, demonstrate functional cell replacement. Apparent benefit may reflect material transfer, trophic rescue, residual host function or procedural and measurement effects. This critical narrative review uses a structured PubMed search covering January 2020 to August 2026, supplemented by seminal studies, to assess retinal pigment epithelium (RPE), photoreceptor, retinal sheet or organoid, and retinal ganglion cell (RGC) transplantation. We separate mechanistic attainment, downstream outcomes and claim-specific causal confidence. Authentic RPE replacement requires donor epithelial function across the host interface, without new synapses. Photoreceptor replacement requires donor phototransduction and transmission to host retinal circuitry; composite grafts additionally require identification of the active donor components. RGC replacement requires both retinal afferent integration and functional reconnection with appropriate central targets. Selected photoreceptor studies demonstrate persuasive local physiological coupling, but durability, donor necessity and generalisability remain incompletely established. Human evidence principally supports feasibility, safety and graft-associated anatomy, rather than convincingly donor-mediated visual restoration. We propose a non-linear evidence framework in which outcomes cannot substitute for secure donor provenance, cell-specific function or host–graft coupling. Spatial concordance, durability, controls, disease-model relevance and experimental unit should qualify every claim.
SN - 2073-4409
ER -