OCULAR TOXICITY OF 2',3'-DIDEOXYINOSINE

2 '，3'-二脱氧肌苷（ddI）是一种嘌呤类似物， 目前用于治疗获得性 免疫缺陷综合征（艾滋病）。 ddI被用于治疗 成人和儿童的临床方案。 这样做的目的 本研究旨在前瞻性随访接受ddI治疗的患者， 继发于药物毒性的眼部并发症的发展。 在95名有症状（CDC P-2级）的HIV感染儿童中， 在一项I-II期研究中， 5例发生周边性视网膜色素萎缩 在ddI治疗期间的上皮。 最多的两个孩子 严重的视网膜萎缩以最高剂量被纳入研究 研究水平（540 mg/m2/天）。 眼电图为 三名视网膜毒性患者中有一名异常， 测试. 一组75名接受ddI治疗的成年人正在接受随访， 定期进行眼底检查和眼电图检查。 在 与儿童的结果相反，没有证据表明 用ddI治疗的HIV感染成人的视网膜毒性。 观察ddI对大鼠视网膜色素上皮细胞的作用 (RPE)细胞，大鼠肺细胞系（CCL 149），以及人羊膜 细胞系（WISH）。 在短期毒性研究中，ddI不会改变细胞 通过台盼蓝排除法测定的生存力，或细胞增殖， 通过随时间推移的总活细胞计数测定。 未来体外毒性 将对人RPE细胞进行研究。 此外，本发明还提供了一种方法， 放射性标记的ddI将用于评价ddI的浓度 被RPE和其他细胞吸收。

2',3'-Dideoxyinosine (ddI) is a purine analog with antiretroviral activity currently used to treat patients with the acquired immunodeficiency syndrome (AIDS). ddI is being used to treat both adults and children in clinical protocols at NIH. The purpose of this study is to follow patients treated with ddI prospectively and observe the development of ocular complications secondary to drug toxicity. Of 95 children with symptomatic (CDC class P-2) HIV infection enrolled in a phase I-II study to assess the safety and antiretroviral activity of ddI, 5 developed peripheral atrophy of the retinal pigment epithelium during ddI therapy. The two children with the most severe retinal atrophy were enrolled in the study at the highest dose level studied (540 mg/m-squared/day). Electro-oculograms were abnormal in one of three patients with retinal toxicity who could be tested. A group of 75 adults treated with ddI are being followed with periodic fundus examinations and electro-oculograms. In contrast to the results in children, there has been no evidence of retinal toxicity in HIV-infected adults treated with ddI. The effects of ddI were evaluated on rat retinal pigment epithelial (RPE) cells, the rat lung cell line (CCL 149), and on the human amnion cell line (WISH). In short-term toxicity studies, ddI did not alter cell viability, as determined by trypan blue exclusion, or cell proliferation, assayed by total viable cell counts over time. Future in vitro toxicity studies will be performed on human RPE cells. In addition, radiolabeled ddI will be used to evaluate the concentration of ddI taken up by RPE and other cells.