Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma.
Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma.
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DOI：
10.1371/journal.pone.0043199
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Krishnamoorthy RR
中科院分区：
文献类型：
--
作者：
Minton AZ;Phatak NR;Stankowska DL;He S;Ma HY;Mueller BH;Jiang M;Luedtke R;Yang S;Brownlee C;Krishnamoorthy RR
青光眼是一种视神经病变，通常与眼内压（IOP）升高相关，其特征为视神经变性、视盘杯状和视网膜神经节细胞缺失，这可能导致视力丧失。内皮素-1（ET-1）是一种由21个氨基酸组成的血管活性肽，在青光眼的发病机制中起关键作用;然而，介导这些作用的受体尚未确定。在当前的研究中，内皮素B（ET B）受体的表达进行了评估，在体内，在莫里森的青光眼高眼压模型的大鼠。在Brown Norway大鼠中，IOP升高导致视网膜中ETB受体的表达增加，主要在视网膜神经节细胞（RGC）、神经纤维层（NFL）以及内丛状层（IPL）和内核层（INL）中。为了确定ETB受体在神经变性中的作用，Wistar-Kyoto野生型（WT）和ETB受体缺陷型（KO）大鼠用荧光金（FG）进行逆行标记，随后一只眼睛的IOP升高，而对侧眼睛作为对照。WT大鼠持续4周的IOP升高导致明显的RGC损失，KO大鼠的RGC损失显著减弱。此外，与WT大鼠相比，KO大鼠的视神经退行性变化大大减少。总之，升高的眼内压介导的ETB受体表达的增加及其活化可能有助于青光眼中所见的RGC存活率的降低。这些发现提高了使用内皮素受体拮抗剂作为神经保护剂治疗青光眼的可能性。
Glaucoma is an optic neuropathy, commonly associated with elevated intraocular pressure (IOP) characterized by optic nerve degeneration, cupping of the optic disc, and loss of retinal ganglion cells which could lead to loss of vision. Endothelin-1 (ET-1) is a 21-amino acid vasoactive peptide that plays a key role in the pathogenesis of glaucoma; however, the receptors mediating these effects have not been defined. In the current study, endothelin B (ETB) receptor expression was assessed in vivo, in the Morrison's ocular hypertension model of glaucoma in rats. Elevation of IOP in Brown Norway rats produced increased expression of ETB receptors in the retina, mainly in retinal ganglion cells (RGCs), nerve fiber layer (NFL), and also in the inner plexiform layer (IPL) and inner nuclear layer (INL). To determine the role of ETB receptors in neurodegeneration, Wistar-Kyoto wild type (WT) and ETB receptor-deficient (KO) rats were subjected to retrograde labeling with Fluoro-Gold (FG), following which IOP was elevated in one eye while the contralateral eye served as control. IOP elevation for 4 weeks in WT rats caused an appreciable loss of RGCs, which was significantly attenuated in KO rats. In addition, degenerative changes in the optic nerve were greatly reduced in KO rats compared to those in WT rats. Taken together, elevated intraocular pressure mediated increase in ETB receptor expression and its activation may contribute to a decrease in RGC survival as seen in glaucoma. These findings raise the possibility of using endothelin receptor antagonists as neuroprotective agents for the treatment of glaucoma.
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影响因子：
3.3
作者：
Dupuis, J;Goresky, CA;Fournier, A
通讯作者：
Fournier, A
影响因子：
4.4
作者：
Chauhan, BC;LeVatte, TL;Archibald, ML
通讯作者：
Archibald, ML
影响因子：
3.4
作者：
GARCIAVALENZUELA, E;SHAREEF, S;SHARMA, SC
通讯作者：
SHARMA, SC
DOI：
10.1016/s0169-328x(00)00256-4
发表时间：
2000-12-28
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Kermer, P;Ankerhold, R;Bähr, M
通讯作者：
Bähr, M
影响因子：
17.8
作者：
Almasieh, Mohammadali;Wilson, Ariel M.;Di Polo, Adriana
通讯作者：
Di Polo, Adriana