Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Comparison Between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-up.

Version 1 : Received: 16 May 2023 / Approved: 17 May 2023 / Online: 17 May 2023 (10:45:28 CEST)

A peer-reviewed article of this Preprint also exists.

Attico, E.; Galaverni, G.; Torello, A.; Bianchi, E.; Bonacorsi, S.; Losi, L.; Manfredini, R.; Lambiase, A.; Rama, P.; Pellegrini, G. Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up. Int. J. Mol. Sci. 2023, 24, 11522. Attico, E.; Galaverni, G.; Torello, A.; Bianchi, E.; Bonacorsi, S.; Losi, L.; Manfredini, R.; Lambiase, A.; Rama, P.; Pellegrini, G. Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up. Int. J. Mol. Sci. 2023, 24, 11522.

Abstract

Total bilateral Limbal Stem Cells 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 non-physiological 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 had been challenging. Previously proposed markers were shown co-expressed by the 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 cells, identifying PITX2 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 cor-neal samples derived from a COMET-treated aniridic patient. Moreover, we found novel angiogenesis-related factors 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 the transplanted cornea.

Keywords

aniridia; biomarker; COMET; cornea; LSCD; neovascularization; oral mucosa; PITX2; ocular surface

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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