Nitric oxide synthase-II is expressed in severe corneal alkali burns and inhibits neovascularization

PURPOSE. Inducible nitric oxide synthase (NOS-II) is expressed in many infl ammatory conditions. The implication of nitric oxide (NO) in angiogenesis r emains controversial. The role of NOS-II and its influence on angiogenesis in corneal neovascularization is unknown and was investigated in this study . METHODS. A mouse model of corneal neovascularization induced by chemical ca uterization was used. NOS-II mRNA expression was analyzed by reverse transc riptase-polymerase chain reaction, and NOS-II protein was studied in situ b y immunohistochemical analysis of the cornea. The influence of NOS-II on ne ovascularization was determined by comparison of vessel development in "nor mal" wild-type mice and mice with a targeted disruption of the NOS-II gene. RESULTS. NOS-II mRNA was induced to very high levels after corneal cauteriz ation and remained upregulated throughout the disease. Migratory cells in t he center of the cauterization area expressed NOS-II protein. The neovascul ar response in mice lacking the NOS-II gene was significantly stronger than in wild-type mice, and the difference increased over time. CONCLUSIONS. These data are the first evidence that NOS-II is expressed in this model of sterile corneal inflammation. NOS-II expression inhibited ang iogenesis in severe corneal alkali burns.