Nitric oxide synthase-II is expressed in severe corneal alkali burns and inhibits neovascularization.
OBJECTIVE
Inducible nitric oxide synthase (NOS-II) is expressed in many inflammatory conditions. The implication of nitric oxide (NO) in angiogenesis remains 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 cauterization was used. NOS-II mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction, and NOS-II protein was studied in situ by immunohistochemical analysis of the cornea. The influence of NOS-II on neovascularization was determined by comparison of vessel development in "normal" 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 cauterization and remained upregulated throughout the disease. Migratory cells in the center of the cauterization area expressed NOS-II protein. The neovascular 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 angiogenesis in severe corneal alkali burns.
Sennlaub
F
F
Développement, Vieillissement et Pathologie de la Rétine, U450, Institut National de la Santé et de la Recherche Médicale, Association Claude Bernard, Paris, France. fsennlau@infobiogen.fr
Courtois
Y
Y
Goureau
O
O
D000818:Animals; D002057:Burns, Chemical / Q000201:enzymology* / Q000473:pathology; D003315:Cornea / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D017931:DNA Primers / Q000737:chemistry; D005126:Eye Burns / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012835:Silver Nitrate
D017931:DNA Primers; D012333:RNA, Messenger; D012835:Silver Nitrate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse