Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up

Total bilateral Limbal Stem Cell Deficiency is a pathologic condition of the ocular surface due to the loss of corneal stem cells. Cultivated oral mucosa epithelial transplantation (COMET) is the only autologous successful treatment for this pathology in clinical application, although abnormal perip...

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Main Authors: Eustachio Attico, Giulia Galaverni, Andrea Torello, Elisa Bianchi, Susanna Bonacorsi, Lorena Losi, Rossella Manfredini, Alessandro Lambiase, Paolo Rama, Graziella Pellegrini
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/14/11522
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author Eustachio Attico
Giulia Galaverni
Andrea Torello
Elisa Bianchi
Susanna Bonacorsi
Lorena Losi
Rossella Manfredini
Alessandro Lambiase
Paolo Rama
Graziella Pellegrini
author_facet Eustachio Attico
Giulia Galaverni
Andrea Torello
Elisa Bianchi
Susanna Bonacorsi
Lorena Losi
Rossella Manfredini
Alessandro Lambiase
Paolo Rama
Graziella Pellegrini
author_sort Eustachio Attico
collection DOAJ
description Total bilateral Limbal Stem Cell Deficiency is a pathologic condition of the ocular surface due to the loss of corneal stem cells. Cultivated oral mucosa epithelial transplantation (COMET) is the only autologous successful treatment for this pathology in clinical application, although abnormal peripheric corneal vascularization often occurs. Properly characterizing the regenerated ocular surface is needed for a reliable follow-up. So far, the univocal identification of transplanted oral mucosa has been challenging. Previously proposed markers were shown to be co-expressed by different ocular surface epithelia in a homeostatic or perturbated environment. In this study, we compared the transcriptome profile of human oral mucosa, limbal and conjunctival cultured holoclones, identifying Paired Like Homeodomain 2 (<i>PITX2</i>) as a new marker that univocally distinguishes the transplanted oral tissue from the other epithelia. We validated PITX2 at RNA and protein levels to investigate 10-year follow-up corneal samples derived from a COMET-treated aniridic patient. Moreover, we found novel angiogenesis-related factors that were differentially expressed in the three epithelia and instrumental in explaining the neovascularization in COMET-treated patients. These results will support the follow-up analysis of patients transplanted with oral mucosa and provide new tools to understand the regeneration mechanism of transplanted corneas.
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spelling doaj.art-240917235a9d4de699fe96b2d2d920822023-11-18T19:40:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124141152210.3390/ijms241411522Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-UpEustachio Attico0Giulia Galaverni1Andrea Torello2Elisa Bianchi3Susanna Bonacorsi4Lorena Losi5Rossella Manfredini6Alessandro Lambiase7Paolo Rama8Graziella Pellegrini9Centre for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia, 41125 Modena, ItalyCentre for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia, 41125 Modena, ItalyCentre for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia, 41125 Modena, ItalyCentre for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia, 41125 Modena, ItalyCentre for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia, 41125 Modena, ItalyUnit of Pathology, Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, ItalyCentre for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia, 41125 Modena, ItalyDepartment of Sense Organs, Sapienza University of Rome, 00169 Rome, ItalySC Ophathalmology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, ItalyCentre for Regenerative Medicine “Stefano Ferrari”, University of Modena and Reggio Emilia, 41125 Modena, ItalyTotal bilateral Limbal Stem Cell Deficiency is a pathologic condition of the ocular surface due to the loss of corneal stem cells. Cultivated oral mucosa epithelial transplantation (COMET) is the only autologous successful treatment for this pathology in clinical application, although abnormal peripheric corneal vascularization often occurs. Properly characterizing the regenerated ocular surface is needed for a reliable follow-up. So far, the univocal identification of transplanted oral mucosa has been challenging. Previously proposed markers were shown to be co-expressed by different ocular surface epithelia in a homeostatic or perturbated environment. In this study, we compared the transcriptome profile of human oral mucosa, limbal and conjunctival cultured holoclones, identifying Paired Like Homeodomain 2 (<i>PITX2</i>) as a new marker that univocally distinguishes the transplanted oral tissue from the other epithelia. We validated PITX2 at RNA and protein levels to investigate 10-year follow-up corneal samples derived from a COMET-treated aniridic patient. Moreover, we found novel angiogenesis-related factors that were differentially expressed in the three epithelia and instrumental in explaining the neovascularization in COMET-treated patients. These results will support the follow-up analysis of patients transplanted with oral mucosa and provide new tools to understand the regeneration mechanism of transplanted corneas.https://www.mdpi.com/1422-0067/24/14/11522aniridiabiomarkerCOMETcorneaLSCDneovascularization
spellingShingle Eustachio Attico
Giulia Galaverni
Andrea Torello
Elisa Bianchi
Susanna Bonacorsi
Lorena Losi
Rossella Manfredini
Alessandro Lambiase
Paolo Rama
Graziella Pellegrini
Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up
International Journal of Molecular Sciences
aniridia
biomarker
COMET
cornea
LSCD
neovascularization
title Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up
title_full Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up
title_fullStr Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up
title_full_unstemmed Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up
title_short Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up
title_sort comparison between cultivated oral mucosa and ocular surface epithelia for comet patients follow up
topic aniridia
biomarker
COMET
cornea
LSCD
neovascularization
url https://www.mdpi.com/1422-0067/24/14/11522
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