實驗性自體免疫前葡萄膜炎中Lymphotactin及其受體表現之生物疾病分子醫學研究

Molecular Study of Biological Disease - Expression of Lymphotactin, and Its Receptor in Lewis Rats with Experimental Autoimmune Anterior Uveitis

急性前葡萄膜炎是人類最常見的葡萄膜炎型式。此眼疾會明顯導致視力障礙而且其確切的致病機制尚未有定論。本研究在實驗性自體免疫前葡萄膜炎的分子醫學機制研究中，成功地建立了路易斯大鼠的活體動物模式。因而在此實驗中，我們探究了實驗性自體免疫前葡萄膜炎中能將特定白血球分群細胞吸引到眼部發炎部位的一種趨化激素lymphotactin及其受體的表現。我們觀察到前房水中白血球的數量隨著虹膜與睫狀體的發炎狀態惡化而增加而且因lymphotactin及其受體於疾病早期的虹膜與睫狀體中即有此趨化激素基因核酸序列的相關表現。因而在其前房水中lymphotactin蛋白質表現量亦於發炎狀態較高舉時有較高濃度產生。進而我們探究了流式細胞儀的分析結果顯示具有lymphotactin抗體呈色的CD8+毒殺型T細胞數量亦隨著發炎狀態惡化而增加。總而言之，毒殺型T細胞所產生的lymphotactin是實驗性自體免疫前葡萄膜炎致病機制的重要角色而且參與疾病早期發炎狀態時特定炎症細胞進入到虹膜與睫狀體的徵集。因此實驗性自體免疫前葡萄膜炎的虹膜與睫狀體之趨化激素lymphotactin及其受體的調節研究分析應有助於呈現疾病進程的機制進而發展有效的生化檢驗方法與阻斷此致病機制來緩解與治療人類的急性前葡萄膜炎。

Acute anterior uveitis (AAU) is the most common form of uveitis in humans. It can cause significant visual impairment and the exact mechanism of AAU has yet to be determined. We have successfully created au animal model of Experimental Autoimmune Anterior Uveitis (EAAU) in Lewis rat. In this experiment, e studied the expression of lymphotactin-a chemokine w Inch attracts lymphocytes to inflammation sites in the EAAU. We observed that the leukocytes of aqueous humor increased with the severity of inflammation of iris/ciliary body. There were specific lymphotactin and its receptor messenger RNA expressions in iris/cilicary body in the early stage of disease. The expression of lymphotactin receptor in iris/ciliary body correlated with that of lymphotactin. Furthermore, the protein levels of lymphotactin in aqueous humor also correlated with the disease process. Flow cytometry analysis revealed that there was increasing number of CD8(superscript +) cytotoxic T cells with positive lymphotactin staining with the severity degree of inflammation. In conclusion, lymphotactin played an important role in the pathogenesis of EAAU. It was produced by cytotoxic T lymphocytes and participated in the early stage of inflammation to attract more inflammatory cells to the iris/ciliary body. Analyses of molecular mechanisms for the regulation of chemokine and chemokine receptors in the iris/ciliary bodies of rats EAAU should help to reveal the mechanisms of the disease process and to develop effective inspect on and therapy for patients with AAU with drugs that block the activation of inflammatory signaling pathways.