Loss and restoration of immune privilege in eyes with corneal neovascularization

Abstract

PURPOSE: To delineate the time course for loss of immune privilege after induction of corneal neovascularization (NV), and to test whether treatment with angiostatic agents can restore the eye's capacity to induce anterior chamber-associated immune deviation (ACAID). METHODS: Corneal NV in murine eyes was induced by placement of intrastromal sutures. At different time points after NV induction, study eyes were initiated on a 10-day regimen of one of a variety of anti-inflammatory or angiostatic agents. After the completion of their treatment regimen, eyes were tested as to whether they could support ACAID. To test whether any observed effect on the delayed-type hypersensitivity response was because of a systemic absorption of the topically applied medication, certain animals had only their fellow eyes treated. RESULTS: Inflammatory corneal NV leads to the loss of immune privilege during the first week of the NV induction. Left untreated, these eyes remain incapable of supporting ACAID, even weeks after the initial corneal insult. However, when treatment with an anti-inflammatory agent is initiated during the first 2 weeks after the NV induction, these eyes show a restored capacity for ACAID induction, and this appears to be unrelated to any systemic effect of the treatment regimen. Treatment started at later time points is not capable of restoring the eye's normal capacity for inducing deviant immunity. CONCLUSIONS: Corneal neovascularization leads to loss of immune privilege in the anterior segment manifested as the inability to sustain ACAID. Moreover, topical angiostatic strategies can lead to restoration of immune privilege when instituted sufficiently early in the course of the neovascular response.