MOLECULAR MECHANISM OF OCULAR MORPHOGENESIS--THE ANT SEG

青光眼是美国第二大致盲原因， 首先是非裔美国人。在许多情况下，眼睛畸形， 尤其是虹膜及相关组织，是导致 青光眼。目前，人们对其基本机制知之甚少。 有助于正常的虹膜发育，因此有助于病理 在异常发育过程中发生的原因尚不清楚。少年派的 实验室发现了一种新的转录因子1MX-1a，它是 对小鼠正常的虹膜发育是必不可少的。缺乏1MX-1a的小鼠 眼睛小，虹膜畸形。在拟议的研究中，PI 计划在五个不同的领域扩展我们目前的发现：第一， 我们的1MX-1a眼发育缺陷的确切性质和时间 突变的小鼠将被确定。二、职能关系 在1MX-1a和其他已知的无虹膜调节基因之间(总计或 将检查人类的虹膜部分缺失)和青光眼。第三, 前段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1MX-1a的细胞参与正常眼的能力 发育将由嵌合小鼠的世代决定。 最后，将分离并定位人类1MX-1a基因，以确定 如果它可能导致遗传性青光眼的话。总而言之， 拟议中的研究应该会带来一些关于 眼前节重要而基本的分子遗传学机制 发展。这些领域的进展最终将导致 在早期诊断、治疗以及可能的情况下取得的基本进展 预防儿童和其他遗传性青光眼。

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.