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.

慢性眼高血压（COH）是在大鼠中通过粘菌静脉烧伤进行的，以诱导视网膜神经节细胞（RGC）凋亡。我们发现，激活了胰岛素 / IGF-1 / AKT途径以抵消该模型视网膜中的凋亡。这一发现表明，抗凋亡信号可能本质地激活了glaucomatus视网膜，尽管其激活的大小不足以抑制RGC凋亡的发展。我们还发现了带有COH的视网膜中神经胶质反应性的特征变化。胶质原纤维酸性蛋白通常局限于星形胶质细胞，在用COH的眼睛中表达。眼内压后表达的改变持续，并在长期随访中发生在对侧眼中。自身免疫性与青光眼神经病的发展有关，尽管该机制仍然未知。上述观察结果表明，一只眼睛中的眼内压升高可能会通过免疫反应通过尚未确定的机制来影响对侧眼的神经胶质功能。据报道，视网膜神经元的凋亡和神经胶质反应性的凋亡甚至在糖尿病性视网膜中甚至在糖尿病性视网膜中观察到了改变，甚至在糖尿病性视网膜中也被观察到微管膜病的发育。越来越多的证据表明，多种局部眼部低压性不仅会降低造成体内压力，而且在视网膜中发挥神经保护作用。在链蛋白酶诱导的糖尿病大鼠的视网膜中，激活的caspase 3和神经元凋亡的免疫反应性增加了，当局部给药时，当前列腺素F2α类似物的前列腺素F2α类似物拉拉坦前列体时，这会逆转。 LATANOPORS在视网膜中特异性增强了p44/p42 rnitogen活化蛋白激酶的磷酸化，而不是Akt的磷酸化。这些发现为可能的药理干预措施开辟了新的途径，以抑制糖尿病性视网膜病的神经退行性变化。

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