Tissue-engineered anterior segment eye cultures demonstrate hallmarks of conventional organ culture.
Aqueous humor outflow
Ocular anterior segment perfusion culture
Tissue engineering
Trabecular meshwork
Journal
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
ISSN: 1435-702X
Titre abrégé: Graefes Arch Clin Exp Ophthalmol
Pays: Germany
ID NLM: 8205248
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
received:
29
07
2022
accepted:
16
11
2022
revised:
11
11
2022
medline:
1
5
2023
pubmed:
25
12
2022
entrez:
24
12
2022
Statut:
ppublish
Résumé
Glaucoma is a blinding disease largely caused by dysregulation of outflow through the trabecular meshwork (TM), resulting in elevated intraocular pressure (IOP). We hypothesized that transplanting TM cells into a decellularized, tissue-engineered anterior segment eye culture could restore the outflow structure and function. Porcine eyes were decellularized with freeze-thaw cycles and perfusion of surfactant. We seeded control scaffolds with CrFK cells transduced with lentiviral vectors to stably express eGFP and compared them to scaffolds seeded with primary TM cells as well as to normal, unaltered eyes. We tracked the repopulation behavior, performed IOP maintenance challenges, and analyzed the histology. Transplanted cells localized to the TM and progressively infiltrated the extracellular matrix, reaching a distribution comparable to normal, unaltered eyes. After a perfusion rate challenge to mimic a glaucomatous pressure elevation, transplanted and normal eyes reestablished a normal intraocular pressure (transplanted = 16.5 ± 0.9 mmHg, normal = 16.9 ± 0.9). However, eyes reseeded with eGFP-expressing CrFK cells could not regulate IOP, remaining high and unstable (27.0 ± 6.2 mmHg) instead. Tissue-engineered anterior segment scaffolds can serve as readily available, scalable ocular perfusion cultures. This could reduce dependency on scarce donor globes in outflow research and may allow engineering perfusion cultures with specific geno- and phenotypes.
Sections du résumé
BACKGROUND
BACKGROUND
Glaucoma is a blinding disease largely caused by dysregulation of outflow through the trabecular meshwork (TM), resulting in elevated intraocular pressure (IOP). We hypothesized that transplanting TM cells into a decellularized, tissue-engineered anterior segment eye culture could restore the outflow structure and function.
METHODS
METHODS
Porcine eyes were decellularized with freeze-thaw cycles and perfusion of surfactant. We seeded control scaffolds with CrFK cells transduced with lentiviral vectors to stably express eGFP and compared them to scaffolds seeded with primary TM cells as well as to normal, unaltered eyes. We tracked the repopulation behavior, performed IOP maintenance challenges, and analyzed the histology.
RESULTS
RESULTS
Transplanted cells localized to the TM and progressively infiltrated the extracellular matrix, reaching a distribution comparable to normal, unaltered eyes. After a perfusion rate challenge to mimic a glaucomatous pressure elevation, transplanted and normal eyes reestablished a normal intraocular pressure (transplanted = 16.5 ± 0.9 mmHg, normal = 16.9 ± 0.9). However, eyes reseeded with eGFP-expressing CrFK cells could not regulate IOP, remaining high and unstable (27.0 ± 6.2 mmHg) instead.
CONCLUSION
CONCLUSIONS
Tissue-engineered anterior segment scaffolds can serve as readily available, scalable ocular perfusion cultures. This could reduce dependency on scarce donor globes in outflow research and may allow engineering perfusion cultures with specific geno- and phenotypes.
Identifiants
pubmed: 36565327
doi: 10.1007/s00417-022-05915-z
pii: 10.1007/s00417-022-05915-z
pmc: PMC10148776
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1359-1368Subventions
Organisme : NEI NIH HHS
ID : K08EY022737
Pays : United States
Organisme : NEI NIH HHS
ID : P30-EY08098
Pays : United States
Organisme : NEI NIH HHS
ID : K08EY022737
Pays : United States
Organisme : NEI NIH HHS
ID : P30-EY08098
Pays : United States
Informations de copyright
© 2022. The Author(s).
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