Optimized laboratory techniques for assessing the quality of pre-stripped DMEK grafts

Abstract This study addressed limitations in calcein-AM-based endothelial viability assays, specifically focusing on pre-stripped DMEK grafts. Key challenges included the suboptimal calcein staining and the incompatibility of the viability assay with subsequent immunofluorescence (IF). Using human c...

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Main Authors: Tomy Sagnial, Sandrine Ninotta, Paul Goin, Inès Aouimeur, Louise Parveau, Sylvain Poinard, Oliver Dorado Cortez, Olfa Ben Moussa, Hanielle Vaitinadapoule, Anne-Sophie Gauthier, Philippe Gain, Gilles Thuret, Zhiguo He
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Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-91512-z
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author Tomy Sagnial
Sandrine Ninotta
Paul Goin
Inès Aouimeur
Louise Parveau
Sylvain Poinard
Oliver Dorado Cortez
Olfa Ben Moussa
Hanielle Vaitinadapoule
Anne-Sophie Gauthier
Philippe Gain
Gilles Thuret
Zhiguo He
author_facet Tomy Sagnial
Sandrine Ninotta
Paul Goin
Inès Aouimeur
Louise Parveau
Sylvain Poinard
Oliver Dorado Cortez
Olfa Ben Moussa
Hanielle Vaitinadapoule
Anne-Sophie Gauthier
Philippe Gain
Gilles Thuret
Zhiguo He
author_sort Tomy Sagnial
collection DOAJ
description Abstract This study addressed limitations in calcein-AM-based endothelial viability assays, specifically focusing on pre-stripped DMEK grafts. Key challenges included the suboptimal calcein staining and the incompatibility of the viability assay with subsequent immunofluorescence (IF). Using human corneal grafts, we employed two strategies to optimize calcein staining. Firstly, we improved calcein staining in corneal endothelium by adjusting calcein-AM concentration and diluent, resulting in a threefold increase in fluorescence intensity with 4 µM calcein in Opti-MEM compared to the conventional 2 µM calcein in PBS. Secondly, introducing the trypan blue (TB) post-viability assay greatly reduced non-specific fluorescence, enhancing the contrast of calcein staining. This improvement significantly and importantly decreased both inter-operator’s variability and the time required for viability counting. For the subsequent double IF, an extensive wash is recommended on the fixed and permeabilized graft after the viability assay, which was carried out using Hoechst-Calcein (HC) labeling. The simple technical tips outlined in this study are not only effective for pre-stripped DMEK grafts but may also prove beneficial for other types of corneal grafts, such as PK and DSAEK.
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spelling doaj-art-d30259a85e2e4864a80be3eb4f8c20722025-08-20T01:57:49ZengNature PortfolioScientific Reports2045-23222025-03-0115111310.1038/s41598-025-91512-zOptimized laboratory techniques for assessing the quality of pre-stripped DMEK graftsTomy Sagnial0Sandrine Ninotta1Paul Goin2Inès Aouimeur3Louise Parveau4Sylvain Poinard5Oliver Dorado Cortez6Olfa Ben Moussa7Hanielle Vaitinadapoule8Anne-Sophie Gauthier9Philippe Gain10Gilles Thuret11Zhiguo He12Laboratory of Biology, Engineering and Imaging for Ophthalmology (BiiO), Faculty of Medicine, Health Innovation Campus, Jean Monnet UniversityLaboratory of Biology, Engineering and Imaging for Ophthalmology (BiiO), Faculty of Medicine, Health Innovation Campus, Jean Monnet UniversityLaboratory of Biology, Engineering and Imaging for Ophthalmology (BiiO), Faculty of Medicine, Health Innovation Campus, Jean Monnet UniversityLaboratory of Biology, Engineering and Imaging for Ophthalmology (BiiO), Faculty of Medicine, Health Innovation Campus, Jean Monnet UniversityLaboratory of Biology, Engineering and Imaging for Ophthalmology (BiiO), Faculty of Medicine, Health Innovation Campus, Jean Monnet UniversityLaboratory of Biology, Engineering and Imaging for Ophthalmology (BiiO), Faculty of Medicine, Health Innovation Campus, Jean Monnet UniversityLaboratory of Biology, Engineering and Imaging for Ophthalmology (BiiO), Faculty of Medicine, Health Innovation Campus, Jean Monnet UniversityLaboratory of Biology, Engineering and Imaging for Ophthalmology (BiiO), Faculty of Medicine, Health Innovation Campus, Jean Monnet UniversityLaboratory of Biology, Engineering and Imaging for Ophthalmology (BiiO), Faculty of Medicine, Health Innovation Campus, Jean Monnet UniversityLaboratory of Biology, Engineering and Imaging for Ophthalmology (BiiO), Faculty of Medicine, Health Innovation Campus, Jean Monnet UniversityLaboratory of Biology, Engineering and Imaging for Ophthalmology (BiiO), Faculty of Medicine, Health Innovation Campus, Jean Monnet UniversityLaboratory of Biology, Engineering and Imaging for Ophthalmology (BiiO), Faculty of Medicine, Health Innovation Campus, Jean Monnet UniversityLaboratory of Biology, Engineering and Imaging for Ophthalmology (BiiO), Faculty of Medicine, Health Innovation Campus, Jean Monnet UniversityAbstract This study addressed limitations in calcein-AM-based endothelial viability assays, specifically focusing on pre-stripped DMEK grafts. Key challenges included the suboptimal calcein staining and the incompatibility of the viability assay with subsequent immunofluorescence (IF). Using human corneal grafts, we employed two strategies to optimize calcein staining. Firstly, we improved calcein staining in corneal endothelium by adjusting calcein-AM concentration and diluent, resulting in a threefold increase in fluorescence intensity with 4 µM calcein in Opti-MEM compared to the conventional 2 µM calcein in PBS. Secondly, introducing the trypan blue (TB) post-viability assay greatly reduced non-specific fluorescence, enhancing the contrast of calcein staining. This improvement significantly and importantly decreased both inter-operator’s variability and the time required for viability counting. For the subsequent double IF, an extensive wash is recommended on the fixed and permeabilized graft after the viability assay, which was carried out using Hoechst-Calcein (HC) labeling. The simple technical tips outlined in this study are not only effective for pre-stripped DMEK grafts but may also prove beneficial for other types of corneal grafts, such as PK and DSAEK.https://doi.org/10.1038/s41598-025-91512-zPre-stripped DMEK graftsEye bankEndothelial viabilityCalcein-AMEndothelial cell density (ECD)Viable ECD
spellingShingle Tomy Sagnial
Sandrine Ninotta
Paul Goin
Inès Aouimeur
Louise Parveau
Sylvain Poinard
Oliver Dorado Cortez
Olfa Ben Moussa
Hanielle Vaitinadapoule
Anne-Sophie Gauthier
Philippe Gain
Gilles Thuret
Zhiguo He
Optimized laboratory techniques for assessing the quality of pre-stripped DMEK grafts
Scientific Reports
Pre-stripped DMEK grafts
Eye bank
Endothelial viability
Calcein-AM
Endothelial cell density (ECD)
Viable ECD
title Optimized laboratory techniques for assessing the quality of pre-stripped DMEK grafts
title_full Optimized laboratory techniques for assessing the quality of pre-stripped DMEK grafts
title_fullStr Optimized laboratory techniques for assessing the quality of pre-stripped DMEK grafts
title_full_unstemmed Optimized laboratory techniques for assessing the quality of pre-stripped DMEK grafts
title_short Optimized laboratory techniques for assessing the quality of pre-stripped DMEK grafts
title_sort optimized laboratory techniques for assessing the quality of pre stripped dmek grafts
topic Pre-stripped DMEK grafts
Eye bank
Endothelial viability
Calcein-AM
Endothelial cell density (ECD)
Viable ECD
url https://doi.org/10.1038/s41598-025-91512-z
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