Bullwhip neurons in the retina regulate the size and shape of the eye
Bullwhip neurons in the retina regulate the size and shape of the eye
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DOI：
10.1016/j.ydbio.2008.02.023
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发表时间：
2008-05-01
影响因子：
2.7
通讯作者：
Wynne, Angela
中科院分区：
文献类型：
--
作者：
Fischer, Andy J.;Ritchey, Eric R.;Wynne, Angela
牛鞭细胞和迷你牛鞭细胞是非常规类型的视网膜神经元，利用神经肽类胰升糖素、类胰升糖素和P物质。这些细胞参与调控鸡视网膜周缘带神经前体细胞的增殖。本研究的目的是探讨牛鞭细胞在调节眼球大小和形状中的作用。我们发现，在出生后第7天，玻璃体内注射秋水仙碱会破坏绝大多数(类似于98%)牛鞭细胞和迷你牛鞭细胞及其肽能终末，这些细胞集中在眼睛赤道附近的CMZ。有趣的是，秋水仙碱治疗导致眼球过度生长，包括赤道直径的扩大，但不包括轴长。眼内注射胰高血糖素完全阻止了秋水仙素治疗所发生的赤道扩张。在视网膜未受损的眼睛中，外源性高血糖素抑制了赤道眼的生长，而高血糖素受体拮抗剂导致了赤道眼的过度生长。此外，增加或减少眼睛生长速度的视觉刺激分别导致牛鞭细胞中即刻早期基因egrl的下调或上调；这表明牛鞭细胞的活动受到生长引导视觉线索的调节。我们发现，高血糖素受体在眼睛赤道区的纤维巩膜和软骨性巩膜细胞中表达。综上所述，这些发现表明，从牛鞭和迷你牛鞭细胞的末端释放的胰高血糖素肽以一种视觉依赖的方式调节赤道巩膜的生长。虽然牛鞭细胞和迷你牛鞭细胞并不丰富，每个视网膜不到1000个细胞，但它们对眼睛发育的影响是巨大的，包括视觉引导的眼睛生长。(C)2008 Elsevier Inc.保留所有权利。
Bullwhip and mini-bullwhip cells are unconventional types of retinal neurons that utilize the neuropeptides glucagon, glucagon-like peptide I (GLP1) and substance P. These cells have been implicated in regulating the proliferation of neural progenitors in the circumferential marginal zone (CMZ) of the chicken retina. The purpose of this study was to investigate the roles of the bullwhip cells in regulating ocular size and shape. We found that intravitreal delivery of colchicine at postnatal day 7 destroys the vast majority (similar to 98%) of the bullwhip and mini-bullwhip cells and their peptidergic terminals that are concentrated in the CMZ near the equator of the eye. Interestingly, colchicine-treatment resulted in excessive ocular growth that involved the expansion of equatorial diameter, but not axial length. Intraocular injections of glucagon completely prevented the equatorial expansion that occurs with colchicine-treatment. In eyes with undamaged retinas, exogenous glucagon suppressed equatorial eye growth, whereas glucagon receptor antagonists caused excessive equatorial growth. Furthermore, visual stimuli that increase or decrease rates of ocular growth caused a down- or up-regulation, respectively, of the immediate early gene Egrl in the bullwhip cells; indicating that the activity of the bullwhip cells is regulated by growth-guiding visual cues. We found that the glucagon receptor was expressed by cells in the fibrous and cartilaginous sclera in equatorial regions of the eye. Taken together, these findings suggest that glucagon peptide released from the terminals of the bullwhip and mini-bullwhip cells regulates the growth of the equatorial sclera in a vision-dependent manner. Although the bullwhip and mini-bullwhip cells are not abundant, less than 1000 cells per retina, their influence on the development of the eye is substantial and includes vision-guided ocular growth. (C) 2008 Elsevier Inc. All rights reserved.