G. Pellegrini et al., LONG-TERM RESTORATION OF DAMAGED CORNEAL SURFACES WITH AUTOLOGOUS CULTIVATED CORNEAL EPITHELIUM, Lancet, 349(9057), 1997, pp. 990-993
Background Complete loss of the corneal-limbal epithelium leads to re-
epithelialisation by bulbar conjunctival cells. Since conjunctival and
corneal-limbal epithelial cells represent two different cell lines, t
his conjunctival healing of the cornea is followed by stromal scarring
, decreased visual acuity, and severe discomfort. Unilateral corneal-l
imbal epithelial defects can be resolved by the transplantation of lim
bal grafts taken from the uninjured eye. However, this procedure requi
res a large limbal graft to be taken from the healthy eye, and is not
possible for bilateral lesions. We investigated the possibility of res
toring the human corneal surface with autologous corneal epithelial sh
eets generated by serial cultivation of limbal cells. Methods Cells we
re cultivated from a 1 mm(2) biopsy sample taken from the limbus of th
e healthy eye of two patients with severe alkali burns, and thus compl
ete loss of the corneal-limbal surface, of one eye. Normal corneal dif
ferentiation was tested with a specific biochemical marker. Autologous
cultured corneal sheets were then grafted onto the damaged eyes of th
e two patients. The patients were followed up at more than 2 years aft
er grafting. Findings We have shown that corneal progenitor cells are
localised in the limbus, that cultured limbal cells generate cohesive
sheets of authentic corneal epithelium, and that autologous cultured c
orneal epithelium restored the corneal surface of two patients with co
mplete loss of the corneal-limbus epithelium. Long-term follow-up show
ed the stability of regenerated corneal epithelium and the striking im
provement in patients' comfort and visual acuity. Interpretation The c
ultivation of corneal epithelium might offer an alternative to patient
s with unilateral lesions and a therapeutic chance to patients with se
vere bilateral corneal-limbal epithelial defects. Our findings give a
new perspective on the treatment of ocular disorders characterised by
stem-cell deficiency.