Regulation of Eye Growth and Development by the Lens

项目总结 眼睛不同部位的发育和生长必须完全协调，才能传递 将视觉图像纠正到大脑。晶状体在一定程度上负责协调眼睛的生长，但我们的 关于潜在机制的知识是不完整的。这个问题将在阿斯特亚纳克斯研究。 Micianus，一种硬骨鱼，由有眼的水面栖息体(水面鱼)和盲穴居组成 形态(穴居鱼)。眼原基最初是在洞鱼的发育过程中形成的，但后来它们停止了 退化，导致成年失明。首先退化的组织是晶状体，然后是 视网膜。将正常的表层鱼胚胎晶状体移植到洞穴鱼视杯中可以恢复完整的 成体穴居鱼的眼睛。几个基因，包括编码抗凋亡蛋白A-晶体蛋白的基因，热 休克蛋白Hsp90？和中线信号形成因子sonic hedgehog(Shh)是候选基因 洞鱼晶状体细胞凋亡的调节因子。晶状体在保护视网膜免受细胞凋亡方面也很重要。 死亡以及角膜和巩膜的正常发育。这个项目的总体目标是确定 晶状体如何通过细胞凋亡而功能失调，以及异常晶状体如何反过来影响整体生长 和眼睛的发育。前两个目标集中在导致晶状体内细胞凋亡的事件上。第一 目的探讨A-晶体蛋白和B-晶体蛋白下调在晶状体细胞凋亡中的作用。第二个目标 将研究HSP90上调在晶状体细胞凋亡中的作用及其在可能的凋亡途径中的存在 带有shh和β-晶状体蛋白基因。最后两个目标移到晶状体外，聚焦于视网膜、角膜和 巩膜，依赖于晶状体发育的光学成分，以及视网膜色素上皮 (RPE)，正常情况下可能与晶状体合作，保护视网膜免受细胞凋亡的影响。第三个目标 研究视网膜基因，这些基因可能涉及控制视网膜生死的途径，以及 晶状体在角膜移行神经脊细胞分化和图案化中的作用 巩膜发育。最终目标将决定RPE是否与晶状体协作调节视网膜 细胞存活。这项提案的目标将结合晶状体显微外科操作，使用细胞和 分子标记、实验性基因过度表达和抑制，以及创造鱼类品系的遗传分析 缺乏可用来检验眼睛生长协调性假说的特定光学成分。这 这项研究旨在为晶状体如何协调眼睛生长和失明提供新的见解 由这一过程中的缺陷造成的。这将填补我们对正常和异常的理解上的一个重大空白 眼睛发育。项目叙事 需要眼睛不同部分的精确发育协调才能将正确的图像传输到 大脑。以盲穴鱼为模型，本研究旨在提供有关这一角色的新信息 人工晶体在协调眼睛发育方面的作用。研究结果将提供对异常眼睛的洞察 发展。

PROJECT SUMMARY Development and growth of the diverse parts of the eye must be perfectly coordinated in order to transmit correct visual images to the brain. The lens is responsible in part for coordinating eye growth but our knowledge about the underlying mechanisms is incomplete. This problem will be studied in Astyanax mexicanus, a teleost fish consisting of an eyed surface dwelling form (surface fish) and a blind cave-dwelling form (cavefish). Eye primordia are initially formed during cavefish development but they subsequently arrest and degenerate, resulting in a blind adult. The first tissue to degenerate is the lens, which is followed by the retina. Transplantation of a normal surface fish embryonic lens into a cavefish optic cup can restore a complete eye in adult cavefish. Several genes, including those encoding the anti-apoptotic protein ¿A-crystallin, the heat shock protein Hsp90¿, and the midline signaling morphogen sonic hedgehog (shh) are candidates for regulators of cavefish lens apoptosis. The lens is also important in protecting the retina from apoptotic cell death and in the normal development of the cornea and sclera. The overall goal of this project is to determine how a lens becomes dysfunctional through apoptosis and how an abnormal lens in turn affects overall growth and development of the eye. The first two aims focus on events leading to apoptosis within the lens. The first aim will investigate the role ¿A-crystallin and ¿B-crystallin downregulation in lens apoptosis. The second aim will examine the role of hsp90¿ upregulation in lens apoptosis and its existence in a putative apoptotic pathway with shh and ¿ -crystallin genes. The last two aims move outside the lens to focus on the retina, cornea and sclera, optic components whose development is dependent on the lens, and the retinal pigment epithelium (RPE), which may normally cooperate with the lens to protect the retina from apoptosis. The third aim investigates retinal genes that are potentially involved in the pathway controlling life or death of the retina, and the role of the lens in the differentiation and patterning of migratory neural crest cells responsible for cornea and sclera development. The final aim will determine if the RPE collaborates with the lens in mediating retinal cell survival. The aims of this proposal will combine lens microsurgical manipulations, the use of cellular and molecular markers, experimental gene overexpression and inhibition, and genetic analysis to create fish strains deficient in specific optic components that can be used to test hypothesis of eye growth coordination. This research is designed to provide new insights into how the lens coordinates eye growth and how blindness can result from defects in this process. This will fill a major gap in our understanding of both normal and abnormal eye development. PROJECT NARRATIVE Precise developmental coordination of the different parts of the eye is required to transmit a correct image to the brain. Using the blind cavefish as a model, this study is designed to provide new information about the role of the ocular lens in coordinating eye development. The results will provide insights into abnormal eye development.