Abstract

Corneal transparency is maintained by the corneal endothelium through its pump and barrier function. Severe corneal endothelial damage results in dysregulation of water flow and eventually causes corneal haziness and deterioration of visual function. In 2013, we initiated clinical research of cell-based therapy for treating corneal decompensation. In that study, we removed an 8-mm diameter section of damaged corneal endothelium without removing Descemet’s membrane (the basement membrane of the corneal endothelium) and then injected cultured human corneal endothelial cells (CECs) into the anterior chamber. However, Descemet’s membrane exhibits clinically abnormal structural features [i.e., multiple collagenous excrescences (guttae) and thickening] in patients with Fuchs endothelial corneal dystrophy (FECD) and the advanced cornea guttae adversely affects the quality of vision, even in patients without corneal edema. The turnover time of cornea guttae is also not certain. Therefore, we used a rabbit model to evaluate the feasibility of Descemet’s membrane removal in the optical zone only, by performing a small 4-mm diameter descemetorhexis prior to CEC injection. We showed that the corneal endothelium is regenerated both on the corneal stroma (the area of Descemet’s membrane removal) and on the intact peripheral Descemet’s membrane, based on the expression of function-related markers and the restoration of corneal transparency. Recovery of the corneal transparency and central corneal thickness was delayed in areas of Descemet’s membrane removal, but the cell density of the regenerated corneal endothelium and the thickness of the central corneal did not differ between the areas with and without residual Descemet’s membrane at 14 days after CEC injection. Here, we demonstrate that removal of a pathological Descemet’s membrane by a small descemetorhexis is a feasible procedure for use in combination with cell-based therapy. The current strategy might be beneficial for improving visual quality after CEC injection as a treatment for FECD.

Highlights

  • The cornea, a transparent tissue located at the front of the eye, allows light to enter the eye

  • As a control for the Feasibility of cell-based therapy combined with descemetorhexis for Fuchs dystrophy in rabbit model corneal endothelial dysfunction model, 6 eyes had the corneal endothelium was totally removed, but circular descemetorhexis (CCD) was not performed and no Rabbit Corneal Endothelial Cell (RCEC) were injected

  • Feasibility of cell-based therapy combined with descemetorhexis for Fuchs dystrophy in rabbit model similar excrescences were observed in non-Fuchs endothelial corneal dystrophy (FECD) donor corneas (Fig 1A, left)

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Summary

Introduction

The cornea, a transparent tissue located at the front of the eye, allows light to enter the eye. Corneal transparency is maintained by the corneal endothelium through a pump and barrier function. The corneal endothelium, which is a monolayer cell sheet located at the anterior chamber aspect of the cornea, regulates the amount of water in the corneal stroma [1]. Severe corneal endothelial damage results in dysregulation of water flow and eventually leads to corneal haziness. The only therapeutic option for treating this corneal endothelial decompensation is corneal transplantation using donor corneas [2]. Strategies for the replacement of damaged corneal endothelium that do not involve a full-thickness corneal transplantation, such as Descemet’s stripping endothelial keratoplasty (DSEK) and Descemet’s membrane endothelial keratoplasty (DMEK), were introduced in 2000s, and these two have gained worldwide prevalence [4,5,6,7,8]. Surgical challenges, long-term cell loss after transplantation, and a shortage of donor cornea tissue still represent major problems associated with corneal transplantation [2, 9]

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