Construction of a Corneal Stromal Equivalent with SMILE-Derived Lenticules and Fibrin Glue.

Houfa Yin,Zhi Fang,Yabo Yang,Jian Ma,Jiaojie Zhou,Qiaomei Tang,Qiuli Fu,Fang Wu,Chao Li,Wenqi Teng,Zhenwei Qin,Wei Zhang,Peijin Qiu

doi:10.1038/srep33848

Abstract

The scarcity of corneal tissue to treat deep corneal defects and corneal perforations remains a challenge. Currently, small incision lenticule extraction (SMILE)-derived lenticules appear to be a promising alternative for the treatment of these conditions. However, the thickness and toughness of a single piece of lenticule are limited. To overcome these limitations, we constructed a corneal stromal equivalent with SMILE-derived lenticules and fibrin glue. In vitro cell culture revealed that the corneal stromal equivalent could provide a suitable scaffold for the survival and proliferation of corneal epithelial cells, which formed a continuous pluristratified epithelium with the expression of characteristic markers. Finally, anterior lamellar keratoplasty in rabbits demonstrated that the corneal stromal equivalent with decellularized lenticules and fibrin glue could repair the anterior region of the stroma, leading to re-epithelialization and recovery of both transparency and ultrastructural organization. Corneal neovascularization, graft degradation, and corneal rejection were not observed within 3 months. Taken together, the corneal stromal equivalent with SMILE-derived lenticules and fibrin glue appears to be a safe and effective alternative for the repair of damage to the anterior cornea, which may provide new avenues in the treatment of deep corneal defects or corneal perforations.

Highlights

Deep corneal defects and corneal perforations can result from various infectious and noninfectious disorders, including microbial keratitis, trauma, degeneration, and immune disorders[1,2]
CK12 was strongly expressed in cells within superficial cell layers (Fig. 4C–E), whereas expression of p63αand ABCG2 was mainly located in the basal cell layer, indicating that the corneal stromal equivalent supported a “limbal” phenotype in the basal layer (Fig. 4I–K)
Basal cells were well attached to the newly synthesized basement membrane and stroma by hemi-desmosomes (Fig. 5D,H). These findings revealed that the constructed corneal stromal equivalent could provide a suitable scaffold for the survival and proliferation of corneal epithelial cells

Summary

Introduction

Deep corneal defects and corneal perforations can result from various infectious and noninfectious disorders, including microbial keratitis, trauma, degeneration, and immune disorders[1,2]. These serious conditions may result in devastating visual consequences and must be managed by immediate treatment to preserve the anatomic integrity of the cornea and prevent complications such as endophthalmitis, secondary glaucoma, and subsequent permanent vision loss[1]. Bhandari et al reported the efficacy of SMILE-derived lenticule patch grafts for the management of corneal microperforations and lamellar corneal defects[18]. We constructed a corneal stromal equivalent with SMILE-derived lenticules and fibrin glue. We determined the suitability of using the corneal stromal equivalent with decellularized lenticules and fibrin glue for corneal stroma reconstruction in vivo

Methods

Results

Conclusion