CD18 and ICAM-1-dependent corneal neovascularization and inflammation after limbal injury.
Extensive limbal injury is a leading cause of irreversible blindness. The destruction of corneal limbal stem cells often results in corneal neovascularization 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 inflammatory cells that invade the cornea. Using a relevant mouse model of limbal injury, we examined the role of CD18 and intercellular adhesion molecule-1 (ICAM-1) in limbal injury-induced neovascularization. The results show that CD18- 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 were similarly reduced by 51% (n = 5, P < 0.003) and 46% (n = 5, P < 0.006), respectively. When VEGF mRNA levels were analyzed, they were reduced by 66% (n = 3, P = 0.004) and 48% (n = 3, P = 0.024), respectively. Taken together, these data identify CD-18 and ICAM-1 as mediators of the inflammatory and VEGF-dependent corneal neovascularization that follows limbal injury. The targeting of CD18 and ICAM-1 may prove useful in the treatment of inflammation-associated neovascularization in the cornea and elsewhere.
Moromizato
Y
Y
Laboratory for Surgical Research, Children's Hospital, Harvard Medical School, and the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
Stechschulte
S
S
Miyamoto
K
K
Murata
T
T
Tsujikawa
A
A
Joussen
A M
AM
Adamis
A P
AP
D000818:Animals; D018821:CD18 Antigens / Q000502:physiology*; D003315:Cornea / Q000098:blood supply*; D016228:Endothelial Growth Factors / Q000235:genetics; D005131:Eye Injuries / Q000150:complications*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007634:Keratitis / Q000209:etiology*; D007958:Leukocyte Count; D008222:Lymphokines / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018821:CD18 Antigens; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D018799:Intercellular Adhesion Molecule-1