An In Vivo Model for Fuchs Endothelial Corneal Dystrophy

Abstract

Purpose: : To evaluate the in vivo functionality of a tissue-engineered corneal endothelium reconstructed using corneal endothelial cells from human patients with Fuchs endothelial corneal dystrophy (FECD).

Methods: : Sixteen healthy cats underwent full-thickness corneal transplantation. Eight animals were grafted with a tissue-engineered (TE) corneal endothelium reconstructed using cultured endothelial cells from patients with FECD (TE-FECD). Two control animals were grafted with a TE corneal endothelium reconstructed using cultured endothelial cells from normal eye bank corneas (TE-normal). Two control animals received a native human cornea. Four other controls were grafted with the stromal carrier only (without endothelial cells). Outcome parameters included graft transparency (0 (opaque) to 4 (clear)), central pachymetry, optical coherence tomography, endothelial cell morphometry, transmission electron microscopy (TEM) and immunostainings of function-related proteins.

Results: : Seven days after transplantation, 6 of 8 TE-FECD grafts, all TE-normal grafts and all native normal control grafts were clear (transparency score greater than 3), while all carrier only control grafts were opaque (transparency score of less than 1). The mean central pachymetry was 755±141 µm for TE-FECD, 524±7 µm for TE-normal, 555±32 µm for native normal and 1188±245 µm for carrier only. TEM showed subendothelial loose fibrillar material deposition in all TE grafts. Other typical but nonspecific findings included: intracellular filaments, cytoplasmic processes, enlarged rough endoplasmic reticulum and lysosomes. No corneal guttae were observed in this early postoperative period. The TE endothelium expressed Na⁺-K⁺/ATPase and Na⁺/HCO3^-. Clusterin immunostaining was faint and similarly expressed in TE-FECD, TE-normal and native grafts.

Conclusions: : Restoration of corneal thickness and transparency demonstrated that the TE-FECD grafts were functional in vivo. This novel TE approach opens the door to future studies on FECD cell rehabilitation.

Keywords: cornea: endothelium • degenerations/dystrophies • transplantation