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J. Cell Biol.,
Volume 145, Number 4, May 17, 1999 769-782
§
* Laboratory of Tissue Engineering, I.D.I.-IRCCS, Istituto Dermopatico dell'Immacolata, Rome, Italy; We have analyzed the proliferative and differentiation potential of human ocular keratinocytes.
Holoclones, meroclones, and paraclones, previously
identified in skin, constitute also the proliferative compartment of the ocular epithelium. Ocular holoclones have the expected properties of stem cells, while transient amplifying cells have variable proliferative potential. Corneal stem cells are segregated in the limbus,
while conjunctival stem cells are uniformly distributed
in bulbar and forniceal conjunctiva. Conjunctival keratinocytes and goblet cells derive from a common bipotent progenitor. Goblet cells were found in cultures of
transient amplifying cells, suggesting that commitment
for goblet cell differentiation can occur late in the life
of a single conjunctival clone. We found that conjunctival keratinocytes with high proliferative capacity give
rise to goblet cells at least twice in their life and, more importantly, at rather precise times of their life history,
namely at 45-50 cell doublings and at ~15 cell doublings before senescence. Thus, the decision of conjunctival keratinocytes to differentiate into goblet cells appears to be dependent upon an intrinsic "cell doubling
clock." These data open new perspectives in the surgical treatment of severe defects of the anterior ocular
surface with autologous cultured conjunctival epithelium.
Division of
Ophthalmology, Ospedale "SS. Giovanni e Paolo," Venice, Italy; and § Department of Ophthalmology, University of "Tor
Vergata," Rome, Italy
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