Analysis of aberrant retinal neuro-glial relationship in glaucoma and diabetic retinopathy

青光眼和糖尿病视网膜病变中异常视网膜神经胶质细胞关系的分析

基本信息

批准号：
16390499
负责人：
NEGI Akira
金额：
$ 5.18万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390499/
关键词：
diabetic retinopathy glaucoma retinal ganglion cells glial cells apoptosis 高眼圧 AKt インスリン IGF-1 糖尿病

项目摘要

Chronic ocular hypertension (COH) was made in rat by episcleral vein cauterization to induce apoptosis of retinal ganglion cells (RGC). We found that the insulin / IGF-1/ Akt pathway was activated to counteract apoptosis in retina of this model. This finding suggests that an anti-apoptotic signal may be intrinsically activated I glaucomatous retina, although the magnitude of its activation is not enough to inhibit the development of RGC apoptosis. We also found characteristic changes in glial reactivity in the retina with COH. Glial fibrillary acidic protein, which expression is normally confined to astrocytes, was expressed in Muller cells in eyes with COH. The altered expression continued after normalization of intraocular pressure and occurred in the contralateral eyes in the long-term follow-up. Autoimmunity has been implicated in the development of glaucomatous optic neuropathy, although the mechanism is still unknown. The above observation indicates the possibility that the elevated intraocular pressure in one eye may affect the glial function in the contralateral eye by immunological responses through yet unidentified mechanisms.Accelerated apoptosis of retinal neurons and altered glial reactivity are reportedly observed in diabetic retina even before the development of microangiopathy as well. Mounting evidence shows that a variety of topical ocular hypotensives not only reduces intraouclar pressure but also exerts a neuroprotective effect in retina. In retina of streptozotocin-induced diabetic rat, immunoreactivity of activated caspase 3 and neuronal apopotosis were increased, which were reversed when latanoprost, a prostaglandin F2 alpha analogue, was topically administered. Latanoprost specifically enhanced phosphorylation of p44/p42 rnitogen activated protein kinase, but not of Akt, in retina. These findings open a new avenue of possible pharmacological intervention to inhibit the neurodegenerative changes in diabetic retinopathy.

通过巩膜外静脉烧灼诱导视网膜神经节细胞（RGC）凋亡，造成大鼠慢性高眼压（COH）。我们发现该模型的视网膜中胰岛素/IGF-1/Akt 通路被激活以抵抗细胞凋亡。这一发现表明，青光眼视网膜中的抗凋亡信号可能本质上被激活，尽管其激活的程度不足以抑制 RGC 细胞凋亡的发展。我们还发现视网膜神经胶质细胞与 COH 的反应性发生了特征性变化。胶质纤维酸性蛋白通常只在星形胶质细胞中表达，但在患有 COH 的眼睛中的 Muller 细胞中表达。在眼压正常化后，表达的改变继续存在，并且在长期随访中发生在对侧眼睛中。尽管机制尚不清楚，但自身免疫与青光眼视神经病的发生有关。上述观察结果表明，一只眼的眼压升高可能会通过免疫反应，通过尚未确定的机制影响对侧眼的神经胶质功能。据报道，在糖尿病视网膜中甚至在发育之前就观察到视网膜神经元加速凋亡和神经胶质反应性改变还有微血管病。越来越多的证据表明，各种局部降眼压药不仅可以降低眼内压，还可以对视网膜发挥神经保护作用。在链脲佐菌素诱导的糖尿病大鼠的视网膜中，活化的 caspase 3 的免疫反应性和神经元凋亡增加，而当局部施用拉坦前列素（一种前列腺素 F2 α 类似物）时，这种情况被逆转。拉坦前列素特异性增强视网膜中 p44/p42 丝原激活蛋白激酶的磷酸化，但不增强 Akt 的磷酸化。这些发现开辟了一条可能的药物干预的新途径，以抑制糖尿病视网膜病变的神经退行性变化。

项目成果

期刊论文数量（28）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Unoprostone isopropyl rescues retinal progenitor cells from apoptosis in vitro.

乌诺前列酮异丙酯在体外可挽救视网膜祖细胞免于凋亡。

DOI：
发表时间：
2004
期刊：
Current Eye Research 29・6
影响因子：
0
作者：
Akiyasu;Kanamori;et al.;Akiyasu Kanamori;Makoto Nakacnura;Akiyasu Kanamori;Hirokazu Mukuno
通讯作者：
Hirokazu Mukuno

Agreement of rebound tonometer in measuring intraocular pressure with three types of applanation tonometers