Role of neurotrophin-4/5 in neural cell death during retinal development and ischemic retinal injury in vivo
Role of neurotrophin-4/5 in neural cell death during retinal development and ischemic retinal injury in vivo
复制标题
DOI：
10.1167/iovs.04-0826
复制
发表时间：
2005-02-01
影响因子：
4.4
通讯作者：
Parada, LF
中科院分区：
文献类型：
--
作者：
Harada, C;Harada, T;Parada, LF
目的.神经营养因子（NT）-4/5和脑源性神经营养因子（BDNF）通过TrkB（一种高亲和力酪氨酸激酶受体）介导细胞存活，并且可以防止各种病理条件下的神经细胞死亡。本研究旨在探讨NT- 4/ 5在视网膜发育过程中神经细胞死亡和缺血性视网膜损伤中的作用。从出生后第0天（P0）到P90，对野生型、NT-4/ 5敲除（KO）和NT- 4/ 5：BDNF双KO小鼠的视网膜发育进行组织学检查.在P42进行缺血性视网膜损伤，定量检测NT- 4/ 5 mRNA表达水平和视网膜细胞死亡程度。真实的实时PCR分析显示缺血视网膜中NT- 4/ 5 mRNA表达增加。在NT- 4/ 5 KO小鼠中，视网膜发育和结构正常，但该品系对P42的缺血性损伤敏感。相反，NT- 4/ 5：BDNF双基因敲除小鼠视网膜发育延迟，并在P42前死亡。这些结果表明，NT- 4/ 5，与其他营养因子相结合，参与了视网膜神经元的发育和变性过程中的出生后存活。
PURPOSE. Neurotrophin ( NT)- 4/ 5 and brain- derived neurotrophic factor ( BDNF) mediate cell survival through TrkB, a high-affinity tyrosine kinase receptor, and may prevent neural cell death in various pathologic conditions. This study was conducted to investigate the function of NT- 4/ 5 in neural cell death during retinal development and ischemic retinal injury.METHODS. Retinal development in wild- type, NT- 4/ 5 knockout ( KO), and NT- 4/ 5: BDNF double- KO mice was histologically examined from postnatal day 0 ( P0) to P90. Ischemic retinal injury was performed at P42, and NT- 4/ 5 mRNA expression level and the extent of retinal cell death was quantitatively examined.RESULTS. Real- time PCR analysis revealed increased NT- 4/ 5 mRNA expression in the ischemic retina. In the NT- 4/ 5 KO mouse, retinal development and structure were normal, but the strain was susceptible to ischemic injury on P42. In contrast, NT- 4/ 5: BDNF double- KO mice showed delayed retinal development and died before P42.CONCLUSIONS. These results suggest that NT- 4/ 5, in combination with other trophic factors, is involved in the postnatal survival of retinal neurons during both development and degeneration.