Purchase this article with an account.
D. A. Sousa, R. Cepeda, A. Woolfenden, J. Demirs, B. Jaffee, J. Sivak, A. Cherry; A Mouse Corneal Debridement Model Reveals Signaling Between Inflammatory Infiltrates and Wound-Edge Epithelium to Induce a Neovascular Response. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5697.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We have characterized an epithelial debridement model of inflammation and angiogenesis in the cornea. Although this response has been known for some time, the relationship between the initiation of inflammatory and angiogenic responses is not well understood. We have explored this question by studying the effects of anti-inflammatory and anti-angiogenic agents in the model.
The corneal epithelium was removed by gentle debridement according to established procedures. Time-course studies were performed over several days to measure the extent of neovascular growth and appearance of inflammatory cells and markers. Either the corticosteroid, dexamethasone, or a VEGF receptor inhibitor, were administered in some experiments to assess their effects on these readouts.
Neovascularization of the corneal stroma reached a plateau by day 6 following complete debridement, before continuing to grow with more variability to later timepoints. Complete removal of the limbal epithelium was necessary in order to elicit a consistent response. Re-epithelialization occurred rapidly, with neutrophils and other inflammatory infiltrates migrating directly beneath the resurfacing epithelial wound edge. Notably, VEGF staining was not observed in inflammatory or stromal cells, but appeared increased in epithelial cells at the wound edge. Treatment with dexamethasone broadly inhibited a panel of angiogenic and inflammatory markers, as well as the VEGF staining in the epithelium. A VEGF receptor inhibitor selectively inhibited only the neovascular response.
We have characterized a mouse corneal debridement model that can be used to assess a variety of angiogenic and inflammatory endpoints. These studies reveal a close association of neutrophil infiltrates with resurfacing wound-edge epithelium to induce a neovascular response.
This PDF is available to Subscribers Only