Journal
BRAIN RESEARCH
Volume 1683, Issue -, Pages 27-35Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2018.01.017
Keywords
EphB/ephrinB reverse signaling; Chronic ocular hypertension; mGluR I; Retinal ganglion cell; Spontaneous firing; Apoptosis
Categories
Funding
- National Natural Science Foundation of China [81790642, 31671078, 81430007]
- International Science & Technology Cooperation Program of China [2015DFA31340]
Ask authors/readers for more resources
EphB/ephrinB reverse signaling is involved in retinal ganglion cell (RGC) apoptosis in experimental glaucoma. Here, we further investigated the mechanisms underlying EphB/ephrinB reverse signaling activation induced RGC apoptosis in a rat chronic ocular hypertension (COH) model, using patch-clamp techniques in retinal slices. In COH retinas, RGCs showed higher spontaneous firing frequency and much more depolarized membrane potential as compared to control, which was mimicked by intravitreally injection of EphB2-Fc, an activator of ephrinB2. The changes in RGC spontaneous firing and membrane potential could be reversed by the tyrosine kinase inhibitor PP2, suggesting that EphB/ephrinB reverse signaling activation induced RGC hyperexcitability. Intravitreal pre-injection of either LY367385 or MPEP, selective mGluR1 and mGluR5 antagonists, also blocked the changes in RGC spontaneous firing and membrane potential. Co-immunoprecipitation experiments showed an interaction between ephrinB2 and group I metabotropic glutamate receptor (mGluR I) (mGluR1/mGluR5). Furthermore, intravitreal pre-injection of the mixture of L-NAME (an NO synthase inhibitor) and XPro1595 (a selective inhibitor of soluble TNE-alpha) could reduce the EphB2-Fc injection induced increase in RGC firing, suggesting that Muller cells might be involved in EphB/ephrinB reverse signaling activation induced change in RGC hyperexcitability. In addition: LY367385/MPEP reduced the numbers of TUNEL-positive RGCs both in EphB2-Fc injected and COH retinas. All results suggest that activation of EphB/ephrinB reverse signaling induces RGC hyperexcitability and apoptosis by interacting with mGluR I in COH rats. Appropriate reduction of EphB/ephrinB reverse signaling could alleviate the loss of RGCs in glaucoma. (C) 2018 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available