Elsevier

Ophthalmology

Volume 114, Issue 6, June 2007, Pages 1080-1088
Ophthalmology

Original Article
Phenotypic Investigation of Human Eyes with Transplanted Autologous Cultivated Oral Mucosal Epithelial Sheets for Severe Ocular Surface Diseases

https://doi.org/10.1016/j.ophtha.2006.09.034Get rights and content

Purpose

To determine the epithelial lineage of origin of surgically removed grafts after autologous cultivated oral mucosal epithelial transplantation (COMET).

Design

Retrospective comparative case series.

Participants

We studied 6 eyes from 5 patients with total corneal stem cell destruction; 3 eyes were from patients with Stevens–Johnson syndrome and 3 eyes had sustained chemical injury.

Methods

Autologous cultivated oral mucosal epithelial sheets on human amniotic membrane (AM) were transplanted onto the ocular surface. Regrafting (2 eyes) or penetrating keratoplasty (4 eyes) was performed after the initial transplantation procedure for further visual rehabilitation.

Main Outcome Measures

The excised grafts were subjected to clinical evaluation and to light, scanning, and transmission electron microscopic (EM) study and to immunohistochemical analysis.

Results

In clinically failed grafts, EM and immunohistochemical analysis disclosed only small areas where the original cultivated oral epithelial cells persisted. Neighboring conjunctival epithelial cells had apparently invaded a large portion of the corneal surface (keratin 3[−], Muc5ac[+]); there were many blood vessels and inflammatory cells. In clinically successful grafts, transplanted cultivated oral epithelial cells survived and had adapted well to the host corneal tissues (keratin 3[+], Muc5ac[−]); there was no infiltration by inflammatory cells, nor was there dissolution of the AM substrate.

Conclusions

We posit that the process of graft opacification after COMET is responsible for the loss of transplanted cultivated oral epithelial cells and that this is followed by conjunctival cell invasion onto the corneal surface. We confirmed that in clinically successfully grafted eyes, autologous cultivated oral epithelial cells survived on the corneal surface and maintained ocular surface integrity.

Section snippets

Subjects

All experimental procedures and clinical applications introduced here were approved by the Institutional Review Board for Human Studies of Kyoto Prefectural University of Medicine; prior informed consent was obtained from all patients in accordance with the tenets of the Declaration of Helsinki for research involving human subjects.

Our study included 3 eyes from 2 patients with SJS and 3 chemically injured eyes from 3 patients. All had undergone autologous COMET; in 4 eyes (4 patients), the

Successful Grafts

Light microscopic examination of removed corneal buttons disclosed some histologic variations. Most areas showed 5 to 6 stratified cell layers and cornealike (oral mucosal sheet) epithelial cells (Fig 1J). Epithelial thickening without epithelial papillar structures was noted in some areas (Fig 1L). The AM substrate was clearly observed throughout the epithelium and there were no inflammatory cells. A cultivated oral epithelial sheet on amniotic membrane is also shown for the purpose of

Discussion

We previously demonstrated that COMET holds promise as a novel surgical treatment for severe OSD such as SJS, ocular cicatricial pemphigoid, and chemical injury.10, 11, 12 This new surgical modality does not require long-term postoperative immunosuppression because there is no risk for postoperative graft rejection. At present, the morphologic and biological corneal phenotypes after COMET are not fully understood. Here we demonstrated for the first time that our clinical slit-lamp findings were

Cited by (0)

Manuscript no. 2006-648.

Supported in part by grants-in-aid for scientific research from the Ministry of Health, Labour and Welfare, Tokyo, Japan (no. H16–Saisei-007), and Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan (Kobe Translational Research Cluster); a research grant from the Kyoto Foundation for the Promotion of Medical Science, Kyoto, Japan; and the Intramural Research Fund of Kyoto Prefectural University of Medicine.

The authors have no financial or propriety interest in the products mentioned in the article.

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