Stromal keratocytes are responsible for wound healing in the cornea following damage. Keratocytes at the site of injury become activated and differentiate to myofibroblasts which secrete extracellular matrix (ECM) to close the wound, a response mediated by transforming growth factor β. Previous work by the same group has shown myofibroblast differentiation and fibrosis in a corneal freeze-injury model at 21 days post challenge. By comparison at six months regeneration or remodelling the cornea had recovered, with corneal fibroblasts aligned to the stromal lamellae. In this paper lamellar keratectomy on rabbit eyes was followed for 60 days by confocal microscopy, with some animals sacrificed at each timepoint. Immediately challenge stromal cell death was apparent. At seven and 21 days after challenge fibroblasts were co-aligned with the collagen, while stromal cells above the wound were randomly arranged, and showed more prominent stress fibres, and alpha smooth muscle actin (a-SMA) expression. After 60 days, cells and matrix had co-aligned into lamellar-like structures, and the cells did not express stress fibres. Corneal haze was reduced at 60 days compared to 21 days. These results show that while fibroblast repopulation of damaged corneal tissue is aligned to collagen lamellae, stromal cells on top of the wound are disorganised and produce a fibrotic ECM. However, after 60 days all stromal cells are aligned to the lamellae and the fibrosis is cleared leading to increased visual acuity. These findings on regeneration and remodelling of corneal tissue have relevance for human disease.

Temporal and spatial analysis of stromal cell and extracellular matrix patterning following lamellar keratectomy.
Kivanany PB, Grose KC, Petroll WM.
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Graham Wallace

Birmingham and Midland Eye Centre, Birmingham, UK.

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