https://scholars.lib.ntu.edu.tw/handle/123456789/199596
標題: | 實驗性自體免疫葡萄膜炎的〝口耐受性〞研究 | 作者: | 林昌平 | 關鍵字: | Animal Model;Autoimmunity;Uveitis;黑色素;自體免疫;動物模型;葡萄膜炎口耐受性 | 公開日期: | 2000 | 出版社: | 臺北市:國立臺灣大學醫學院眼科 | 摘要: | Oral Tolerance Uveitis is one of the leading causes of blindness. It was estimated that IO% of the blindness was caused by uveitis in USA. The treatment is mainly topical and systemic corticosteroid, and some of these patients may require the use of a variety of iminunomodulatory, corticosteroid-sparing agents, such as cyclosporine or cytotoxic agents. To date, clinically oriented approaches have centered on the administration of pharmacologic substances that have a nonspecific effect on the immune response. The development of more effective treatment of organ-specific inflammatory disorders of putative autoimmune origin is an ongoing goal in many specialties of clinical medicine, Recently, alternative therapeutic strategies have been suggested based on our better understanding of immunologic mechanisms that lead to organ-specific inflammatory responses. The induction of immunologic tolerance, defined as a state of specific immunologic unresponsiveness to an antigen after exposure to that antigen, is one such approach that has gained attention recently. One effective method of inducing immunologic tolerance is through the oral administration of antigen. The tolerance induced is called oral tolerance. One feature of oral tolerance is that ¡§bystander¡¨ suppressive effect can be elicited to the organ or tissue that harboring the antigen. Oral tolerance has been tested in various animal models of autoimmune disorders, such as experimental autoimmune encephalomyelitis, collagen and adjuvant arthritis, experimental autoimmune diabetes, and experimental autoimmune uveitis. The effect of oral tolerance has also been tested in several clinical conditions in small scale with encouraging results, such as multiple sclerosis, theurnatoid arthritis, juvenile diabetes, Behcet¡¦s disease and other intractable uveites. The most common disease entity of uveites in Taiwan is acute anterior uveitis (AAU). It is the recurrent nature of AAU that can result in blindness and socioeconomic loss though various complications, including glaucoma, cataract, and cystoid macular edema. Experimental autoimmune anterior uveitis (EAAU) has been established to simulate human AAU, It involves the use of melanin associated antigen extracted from bovine uveal tissue. In this report, we investigated the effect of oral tolerance in EAAU both as primary and secondary prevention, i.e. in unprimed and in primed animals. By feeding Lewis rats with insoluble melanin associated antigen the experimental autoimmune anterior uveitis was not suppressed. This unsuccessful induction of tolerance might be related to the use of insoluble melanin associated antigen, which is pro-inflammatoy itself. To repeat the whole experiment by using soluble MAA may well be the goal of next project. 葡萄膜炎一般認為是一種自休免疫疾病,因反覆發生,造成角膜病變白內障青光眼或視網膜病變,而導致失明。其治療到目前為止一直是以局部或口服腎上腺類固醇或其他免疫抑制劑如環抱靈素等為主要的方法。這類療怯因為是廣泛性、無選擇性的免疫抑制,而有各種相當嚴重的副作用。 口耐受性是指口服一種抗原,身餿對該抗原的反應方式會有所改變。以視網膜可溶性抗(SesAg )為例,在路易氏鼠口服s - -擔(或其它抗原為對照組)數週後再於腳上注射SeeAg 以弓I 發實驗性自體免疫葡萄膜炎。發現口月弘-鰓的一組實驗性自體免疫葡萄膜炎不會發作,而對照組口服其它不相關抗原則會如預期的發病,其抑制作用具抗原選擇性。最近因各種自體免疫疾病的動物模型的建立與應用,而能進一步探討口耐受性在治療與預防自體免疫疾病的可行性。有些疾病在動物模型與在,J 覦模的人體試驗中獲得令人鼓舞的結果,如類風濕性關節炎、多發性硬節症、難纏的葡萄膜炎等。 本報告中使用口服可溶性黑色素相關抗原來防止實驗性自體免疫前葡萄膜炎,因實驗性自體免疫前葡萄膜炎在發病3 必週可幾乎完全復原,再次施打M 曉A 時可弓― 起實驗性自體免疫前葡萄膜炎再發,因此可以研究在初次發病前或發病後讓路易士鼠口服黑色素相關抗原,以研究口耐性初級預防實驗性自體免疫前葡萄膜炎發病或發病後次級預防實驗性自體免疫前葡萄膜炎再發的可能性。(而後者正是臨床上最希望能應用的• )結果是口服不可溶黑色素相關抗原無法抑制實驗性自餿免疫前葡萄膜炎的發生與再發。這可台皂與本實驗中使用的是不可溶黑色素抗原,而黑色素本身即有促發發炎反應的作用有關。使用可溶性黑色素抗原於類似的實驗將是下一個實驗計劃的方向。 |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/26715 | 其他識別: | 892314B002249 | Rights: | 國立臺灣大學醫學院眼科 |
顯示於: | 醫學系 |
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