The function of VEGF-A in lens development: formation of the hyaloid capillary network and protection against transient nuclear cataracts.
The function of VEGF-A in lens development: formation of the hyaloid capillary network and protection against transient nuclear cataracts.
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DOI：
10.1016/j.exer.2008.07.017
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发表时间：
2009-02
影响因子：
3.4
通讯作者：
Beebe, David C.
中科院分区：
文献类型：
--
作者：
Garcia, Claudia M.;Shui, Ying-Bo;Kamath, Meera;DeVillar, Justin;Johnson, Randall S.;Gerber, Hans-Peter;Ferrara, Napoleone;Robinson, Michael L.;Beebe, David C.
关键词：
在哺乳动物胚胎发育的大部分时间里，由玻璃状血管系统分支出来的毛细血管网络包围着晶状体。这些血管被认为对晶状体的生长和成熟很重要，尽管非哺乳动物的脊椎动物的晶状体没有类似的血管。晶状体中VEGF-A的过度表达增加了这些毛细血管的范围，但目前尚不清楚晶状体中的VEGF-A是否是它们形成或存活所必需的。为了解决这个问题，我们删除了镜头中的Vegfa。这阻止了晶状体囊附近毛细血管网络的形成，但没有改变视网膜表面附近的玻璃状血管。出生后晶状体缺乏Vegfa比野生型小，到1个月大时，许多人有轻度核混浊。这些不透明随着年龄的增长而消退。晶状体一生大部分时间处于缺氧状态，VEGF-A的表达常受缺氧诱导因子-1的调控。缺乏Hif1a的晶体大小明显正常，VEGF-A和甘油醛-3-磷酸脱氢酶mRNA水平明显降低，但表面有正常的毛细血管覆盖。我们得出结论，晶状体的VEGF-A对于形成正常的玻璃体血管系统是必要的，这些毛细血管的缺乏是胎儿和出生后早期晶状体发育发育迟缓的最可能原因。在HIF-1功能缺失的情况下，晶状体产生足够的VEGF-A来促进毛细血管的形成。需要进一步的研究来解释在一些缺乏Vegfa的晶状体中所见的轻度混浊的形成及其在生命后期的消退。
A network of capillaries branches from the hyaloid vascular system and surrounds the mammalian lens throughout much of its embryonic development. These vessels are presumed to be important for the growth and maturation of the lens, although the lenses of non-mammalian vertebrates have no comparable vessels. Over expression of VEGF-A in the lens increases the extent of these capillaries, but it is not known whether VEGF-A from the lens is necessary for their formation or survival. To address this question, we deleted Vegfa in the lens. This prevented the formation of the capillary networks adjacent to the lens capsule, but did not alter nearby hyaloid vessels at the surface of the retina. Postnatal lenses lacking Vegfa were smaller than wild type and, by 1 month of age, many had mild nuclear opacities. These opacities regressed with age. The lens is hypoxic throughout most of life and VEGF-A expression is often regulated by the transcription factor, hypoxia inducible factor-1. Lenses lacking Hif1a were of apparently normal size, had markedly reduced levels of mRNA for VEGF-A and glyceraldehyde-3-phosphate dehydrogenase, but had normal-appearing capillaries covering their surface. We conclude that VEGF-A from the lens is necessary for the formation of the normal hyaloid vascular system and that lack of these capillaries was the most likely cause of growth retardation during fetal and early postnatal lens development. In the absence of HIF-1 function, sufficient VEGF-A is produced by the lens to promote capillary formation. Further study is needed to explain the formation of the mild opacities seen in some lenses lacking Vegfa and their regression later in life.
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影响因子：
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Ash, JD;Overbeek, PA
通讯作者：
Overbeek, PA
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