Background to the research

Histology and maintenance of the adult mouse corneal epithelium
The cornea comprises an outer epithelium (ep), stroma (s) and endothelium (en). The corneal epithelium is formed during fetal development and in the adult it is maintained by stem cells in the limbus between the cornea and conjunctiva. Limbal stem cells produce transient amplifying (TA) cells, which populate the basal epithelial layer. These replicate, migrate centrally and produce differentiated cells in the outer layers, which are lost by desquamation.

Research Results

Variegated patterns in the corneal epithelia of LacZ-positive↔LacZ-negative mouse chimeras and X-inactivation mosaics, hemizygous for an X-linked LacZ transgene have provided a novel system for analysis of corneal epithelial maintenance (see figure). At 3 weeks the two cell populations formed a randomly orientated patchwork (A), representing the initial pattern produced during development. In the adult this was replaced by radial stripes (B,C) that emerged from the limbus at ~5 weeks, reflecting the onset of LSC activity and corneal epithelial maintenance by LSCs in the adult. The pattern of stripes in mosaics
(B) and chimeras (C) was consistent with radial inward migration of epithelial cells from the limbus. Stripes often converged at a central clockwise or anticlockwise vortex-like whorl (D).

In Pax6+/- mosaic corneal epithelia, the pattern of stripes was disrupted (E) but in Pax6+/-↔Pax6+/+ chimeras (where only the lacZ-positive cells were Pax6+/+ the Pax6+/- cells formed normal blue stripes (F), suggesting the epithelial cell migration defect was corrected by wildtype cells in the chimera (Collinson et al 2004). The correction of the migration defect could be mediated via wildtype cells in the corneal epithelium, stroma or other eye tissues.

Quantitative analysis of stripe numbers suggested that limbal stem cell function declines with age (Mort et al 2009).

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