Light regulated vascular development of the eye

光调节眼睛血管发育

• 批准号: 8788267
• 负责人: DAVID Richard COPENHAGEN
• 金额: $ 45.09万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8788267
• 关键词: Adopted; Affect; Biological; Blood Vessels; Brain-Derived Neurotrophic Factor; Circadian Rhythms; Complex; Darkness; Data; Defect; Development; Educational process of instructing; Exhibits; Eye; Eye Development; Eye diseases; Fetus; Genetic; Goals; Green Algae; Growth; Health; Heterozygote; Homozygote; Human; Hypoxia; Lead; Light; Mediating; Methods; Modeling; Molecular; Mus; Mutant Strains Mice; Neonatal; Neurons; Obstruction; Optics; Oxygen; Oxygen measurement, partial pressure, arterial; Pathway interactions; Pattern; Photophobia; Phototropism; Planets; Plants; Public Health; Publishing; Regulation; Retinal; Retinal Ganglion Cells; Retinopathy of Prematurity; Risk; Role; Signal Transduction; Stimulus; System; Testing; The Sun; Time; Vascular Endothelial Growth Factors; Vision; Work; dark rearing; fetal; melanopsin; neurotrophic factor; postnatal; pup; response; retina blood vessel structure

DESCRIPTION (provided by applicant): Light is an all-pervasive biological stimulus. Most light on our planet comes from the sun and this is closely reflected in the mechanisms of light response that have evolved. Whether it is the phototropism of a unicellular green alga, the circadian entrainment of plants or high-acuity vision in humans, light elicits a huge variety of biological responses that are of fundamental importance. In this application, we provide evidence that in the mouse (and thus, probably in the human) light is an important stimulus for eye development. Unexpectedly, we found that dark reared neonatal mice exhibit abnormal vascular development in which the regression of hyaloid vessels is retarded and the growth of retinal vessels is promiscuous. The same abnormal growth is observed in light reared mice lacking the photopigment melanopsin. We have strong preliminary evidence that the maldevelopment of the ocular vessels is associated with (1) changes in the retinal level of the neurotrophin BDNF, (2) increased neuron number, and (3) altered VEGF expression level via oxygen demand. Also, surprisingly, the maximal effect of dark rearing is found in pups raised in darkness from E16. Our Central Hypothesis is: Ocular development is regulated by a fetal light-melanopsin-BDNF pathway that regulates neuron number, VEGF expression, and ultimately, postnatal vascular patterning. We propose three experimental aims: (1) To establish whether light activation of the melanopsin pathway in the fetus is necessary and sufficient to regulate vascular development in the eye, (2) to determine how BDNF signaling integrates with light-dependent vascular development, and (3) to define the role of oxygen demand in the light response pathway.

描述（由申请人提供）：光是一种无处不在的生物学刺激。我们星球上的大多数光都来自太阳，这在进化的光反应机理中紧密反映。无论是单细胞绿色藻类的光质主义，昼夜植物的夹带，还是人类的高吸引视觉，光线都引起了各种各样的生物学反应，这具有至关重要的重要性。在此应用中，我们提供的证据表明，在小鼠中（因此，可能在人类中）是眼睛发育的重要刺激。出乎意料的是，我们发现黑暗饲养的新生儿小鼠表现出异常的血管发育，其中透明血管的回归受阻，并且视网膜血管的生长是混乱的。在缺乏光化黑色素蛋白的轻型饲养小鼠中观察到同样的异常生长。我们有强有力的初步证据表明，眼容器的玛尔达开发与（1）神经营养蛋白BDNF的视网膜水平变化有关，（2）神经元数量增加，（3）通过氧气需求改变了VEGF表达水平。同样，令人惊讶的是，黑暗饲养的最大效果是在E16的黑暗中饲养的幼犬中发现的。我们的中心假设是：眼部发育受到调节神经元数，VEGF表达的胎儿光甲虫BDNF途径的调节，最终是出生后血管形式。我们提出了三个实验目的：（1）确定胎儿中黑色素蛋白途径的光激活是否需要且足以调节眼睛中的血管发育，（2）确定BDNF信号如何与光依赖性血管发育集成在一起，以及（3）以界定氧气在光响应途径中的作用。