MOLECULAR MECHANISM OF OCULAR MORPHOGENESIS--THE ANT SEG

青光眼是美国第二大致盲原因， 首先是非洲裔美国人。 在许多情况下，眼睛畸形， 特别是虹膜和相关组织，是导致 青光眼 目前，人们对基本机制知之甚少， 有助于正常的虹膜发育， 在异常发育过程中产生的不被理解。 PI的 实验室已经鉴定出一种新的转录因子，1 mx-1a， 对小鼠正常虹膜发育至关重要。 缺乏1 mx-1a的小鼠 眼睛小虹膜畸形 在研究中，PI 计划在五个不同的领域扩展我们目前的研究结果：首先， 我们的1 mx-1a中眼部发育缺陷的精确性质和时间 将确定突变小鼠。 二、功能关系 1 mx-1a和其他已知的无虹膜调控基因（总或 虹膜的部分丧失）和青光眼。 第三、 眼前节形态发生的新诱导机制 将使用我们生成和/或分离的试剂进行表征。 第四，缺乏1 mx-1a的细胞参与正常眼的能力 发育将通过嵌合小鼠的产生来确定。 最后，人类1 mx-1a基因将被分离和定位，以确定 是否会导致任何遗传性肿瘤 总的来说， 拟议中的研究应该会带来一些关于 眼前节重要和必要的分子遗传学机制 发展 这些领域的进展将最终导致 在早期诊断、治疗和尽可能 预防小儿和其他遗传性肿瘤。

Glaucoma is the second leading cause of blindness in the United States, first among African Americans. In many cases, malformation of the eye, especially the iris and associated tissues, is the underlying cause of glaucoma. At present, little is known about basic mechanisms which contribute to normal iris development and therefore the pathology arising during abnormal development is not understood. The PI's laboratory has identified a new transcription factor, 1mx-1a, which is essential for normal iris development in mice. Mice which lack 1mx-1a have small eyes and a malformed iris. In the proposed research, the PI plans to extend our current findings in five distinct areas: First, the precise nature and timing of ocular developmental defects in our 1mx-1a mutant mice will be determined. Second, the functional relationship between 1mx-1a and other regulatory genes known to aniridia (total or partial loss of iris) and glaucoma in humans will be examined. Third, novel inductive mechanisms underlying anterior segment morphogenesis will be characterized using reagents we have generated and/or isolated. Fourth, the ability of cells lacking 1mx-1a to participate in normal eye development will be determined by the generation of chimeric mice. Finally, the human 1mx-1a gene will be isolated and mapped to determine if it may contribute to any hereditary glaucomas. Taken together, the proposed studies should lead to some of the first insights into important and essential molecular genetic mechanisms of anterior segment development. Progress in these areas will ultimately lead to fundamental advances in early diagnosis, treatment, and where possible prevention of pediatric and other hereditary glaucomas.