Corneal responses to UV radiation
Background. The cornea is an ideal tissue in which to study the cell biology of stratified epithelia, due to its optical clarity, simplicity and exposed anatomical location. Its location also exposes it to ultraviolet radiation (UVR) from sunlight, which contributes to ocular cancers and conditions such as keratoconus.
Aim. To investigate the responses of a stratified epithelium to UVR, we have undertaken live imaging and microscopic analyses of corneas of various reporter strains of mice.
Results. Repeated exposure of mice to low dose UVR over several months results in corneal ectasia, loss of stromal cells, an increase in epithelial basement membrane fragmentation and loss of stromal collagen fibre disorganisation. Coinciding with this is an increase in the turnover of the corneal epithelial cells. Using intravital imaging of Confetti lineage tracing mice, we have shown that a single low dose of UVR, equivalent to about 20min in the sun, causes a substantial increase in epithelial turnover that is sustained for 10 days in the absence of significant inflammation and cell death.
Irradiation of specific areas of the cornea, together with mathematical modelling, indicates that the epithelial cells near the centre of the cornea are the primary target of the UVR, increasing their rate of delamination from the basal cell layers. Imaging of living mouse corneas show that this delamination occurs via a non-canonical form of cell extrusion, in which cells are pushed out of the basal layer by surrounding cells, but are retained on their apical surfaces.
Conclusion. UVR acts directly on the corneal epithelial cells and indirectly on their stem cell precursors to increase delamination and proliferation, respectively. Regulation of delamination from the basal layer by population pressure may be a general mechanism for regulating homeostasis and tissue damage responses in stratified epithelia.