EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN THE EYE FROM ENDOTOXIN-INDUCED UVEITIS RATS

Purpose. Inducible nitric oxide (NO) synthase (iNOS) has been implicat ed in the pathogenesis of endotoxin-induced uveitis (EIU). This study was undertaken to localize the cells, in the eye, which express iNOS d uring EIU in the rat. Methods. EIU was induced in Lewis rats by a sing le foot pad injection of 150 mu g lipopolysaccharide (LPS) from Salmon ella typhimurium. At different time intervals after LPS injection, the authors evaluated ocular inflammation (slit lamp observation), iNOS l ocalization by in situ hybridization, and comparison of OX-42- and ED1 -positive cell appearance and of glial response by specific immunohist ochemistry. Results. iNOS mRNA was not detected in the iris-ciliary bo dy nor in the retina of control rats. It was detected strongly in the epithelial cells of the iris-ciliary body at 6 hours and also in strom al cells of the ciliary processes at 16 hours after LPS injection. In the neuroretina, iNOS mRNA was observed in the inner layers 16 hours a fter LPS injection. iNOS-positive cells were also present in the vitre ous at this time. At 6 and approximately 16 hours after LPS injection, immunohistochemistry experiments revealed a large number of OX-42- an d ED1-positive cells (microglia, macrophages, or polymorphonuclear leu kocytes) colocalized in part with some iNOS-positive cells in the cili ary body and in the retina. Furthermore, expression of iNOS in Muller cells cannot be excluded. Conclusions. These observations confirm that subcutaneous injection of endotoxin dramatically induces NOS mRNA exp ression in the eye, and they demonstrate that epithelial cells of the iris-ciliary body and cells infiltrating the anterior segment of the e ye and the retina are the major source of NO. These results support th e hypothesis that both inflammatory and resident ocular cells are invo lved in iNOS expression during EIU.