Cytokine expression in ocular tissne and theirde in the pathegenesis of Uveitis

我们研究了1）使用细胞培养，哪些细胞因子和/或生长因子可能在眼组织中表达，以及2）这些因子是否在动物模型中实际上在体内表达并且在生理和病理情况中具有某些作用。在培养中，角膜上皮细胞表达内皮素-1，并且该因子促进宿主上皮细胞自身的增殖。这种内皮素存在于泪液中，可能由泪腺产生，其浓度高于血清。内皮素对兔角膜创伤愈合有明显的加速作用。光凝视网膜色素上皮细胞（RPE）在培养中产生TGF-β，光凝RPE的条件培养基抑制血管内皮细胞的增殖。TGF-β的抗体逆转了这种抑制作用，这表明由光凝固的RPE产生的TGF-β作为血管生成抑制剂的作用。在光凝大鼠RPE中也观察到TGF-β的体内增加。在内毒素诱导的葡萄膜炎（内毒素注射引起的眼部炎症）中，我们发现在葡萄膜炎的早期，虹膜睫状体中的驻留细胞产生白细胞介素-1和肿瘤坏死因子。在该葡萄膜炎模型中，还发现虹膜睫状体中的一氧化氮增加。另一方面，发现TGF-β在葡萄膜炎的后期增加，此时炎症几乎减少。我们目前正在研究这些炎症因子是如何参与眼部炎症过程的。

We investigated 1) what cytokines and/or growth factors are possibley expressed in ocular tissues using cell culture, and 2) if these factors are actually expressed in vivo in animal models and have some roles in physiological and pathological situations. In culture, corneal epithelial cells express Endothelin-1 and this factor promotes proliferation of the host, epithelial cells themselves. This Endothelin was found to exist in tear, possibly produced in lacrimal gland, in higher concentration than that in serum. Also, Endothelin actualy fasten the wound heeling in rabbit cornea. The photocoagulated retinal pigment epithelium (RPE) produce TGF-beta in culture, and the conditioned medium of photocoagulated RPE inhibits the proliferation of vascular endothelium. The antibody of TGF-beta reversed this inhibitory effect which suggested the role of TGF-beta produced by photocoagulated RPE as an inhibitor of angiogenesis. The increase in TGF-beta was also observed in vivo in photocoagulated rat RPEs. In endotoxin-induced uveitis, (ocular inflammation caused by lipopolysaccharide injection), We found that Interleukin-1 and Tumor necrosis factors are produced by the resident cells in iris-ciliary body at the early phase of uveitis. Nitric oxide was also found to be increased in iris-ciliary body in this uveitis model. On the other hand, TGF-beta was found to increase in the later phase of uveitis, at which time the inflammation is almost diminished. We are currently sutdying how these inflammatory factors are involved in the process of ocular inflammation.