CD18 and ICAM-1-dependent corneal neovascularization and inflammation after limbal injury

Extensive Limbal injury is a leading cause of irreversible blindness. The d estruction of corneal limbal stem cells often results in corneal neovascula rization and an optically inferior epithelium, Previous work has shown that the neovascularization after limbal injury is vascular endothelial growth factor (VEGF)-dependent, with much of the VEGF emanating from the inflammat ory cells that invade the cornea, Using a relevant mouse model of limbal in jury, we examined the role of CD18 and intercellular adhesion molecule-1 (I CAM-1) in limbal injury-induced neovascularization, The results show that C D18- and ICAM-1-deficient mice developed 35% (n = 5,P = 0.003) and 36% (n = 5, P = 0.002) less neovascularization than strain-specific normal controls , respectively. The corneal neutrophil counts mere similarly reduced by 51% (n = 5, P < 0.003) and 46% (n = 5, P < 0.006), respectively, When VEGF mRN A levels mere analyzed, they were reduced by 66% (n = 3, P = 0.004) and 48% Of = 3,p = 0.024), respectively, Taken together, these data identify CD-18 and ICAM-1 as mediators of the inflammatory and VEGF-dependent corneal neo vascularization that follows limbal injury. The targeting of CD18 and ICAM- 1 may prove useful in the treatment of inflammation-associated neovasculari zation in the cornea and elsewhere.