Calcium channels are involved in EphB/ephrinB reverse signaling‑induced apoptosis in a rat chronic ocular hypertension model.

Publisher: D. A. Spandidos Country of Publication: Greece NLM ID: 101475259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1791-3004 (Electronic) Linking ISSN: 17912997 NLM ISO Abbreviation: Mol Med Rep Subsets: MEDLINE

Original Publication: Athens, Greece : D. A. Spandidos

Apoptosis* ; Signal Transduction*; Calcium Channels/*metabolism ; Ephrins/*metabolism ; Ocular Hypertension/*etiology ; Ocular Hypertension/*metabolism ; Receptors, Eph Family/*metabolism; Animals ; Calcium Channels/genetics ; Chronic Disease ; Disease Models, Animal ; Gene Expression ; Male ; Rats ; Retinal Ganglion Cells/metabolism ; Retinal Ganglion Cells/pathology

Erythropoietin-producing hepatocyte receptor B (EphB)/ephrinB reverse signaling has been revealed to be activated in chronic ocular hypertension (COH) by increasing the apoptosis of retinal ganglion cells (RGCs). However, the exact mechanism is not well understood. The present study investigated the involvement of Ca2+ channels in the apoptosis of RGCs induced by EphB/ephrinB reverse signaling in a rat CHO model, which was established by cauterizing 3 out of the 4 episcleral veins. The expression levels of four voltage‑gated Ca2+ channel subunits (Cav3.1‑3.3 and Cav1.2) were detected using immunofluorescence and western blot analysis. TUNEL staining was performed to assess RGC apoptosis following an injection with the T type Ca2+ channel blocker. Ca2+ channels, mainly the T type, were upregulated in COH rat retinas when compared with the sham group (P<0.01). Additionally, the Cav3.2 subunit of T type calcium channels was predominantly expressed in Müller cells and RGCs, such as ephrinB2. Furthermore, an intravitreal injection of the Ca2+ channel blocker Mibefradil (3 µM) reduced EphB2‑fragment crystallizable region‑induced RGC apoptosis in normal rats. Thus, the results suggest that Ca2+ channels in a COH model may be a pathway involved in ephrinB/EphB signaling‑induced RGC apoptosis.

Pharmacol Ther. 2004 May;102(2):155-74. (PMID: 15163596)
Neurobiol Dis. 2011 Aug;43(2):455-64. (PMID: 21554958)
Cell Signal. 2012 Mar;24(3):606-11. (PMID: 22120527)
Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5567-81. (PMID: 18055806)
Am J Physiol. 1991 Jun;260(6 Pt 1):C1347-51. (PMID: 1647668)
Neuroscience. 2016 Jan 28;313:213-24. (PMID: 26621126)
J Neurosci. 2015 Apr 1;35(13):5409-21. (PMID: 25834064)
Mol Cell Neurosci. 2015 Sep;68:234-43. (PMID: 26255006)
Curr Opin Neurobiol. 2004 Jun;14(3):288-96. (PMID: 15194108)
Curr Opin Ophthalmol. 2000 Apr;11(2):116-20. (PMID: 10848217)
Curr Opin Cell Biol. 2007 Oct;19(5):534-42. (PMID: 17928214)
Nat Neurosci. 2004 Jan;7(1):33-40. (PMID: 14699416)
Invest Ophthalmol Vis Sci. 2012 Feb 13;53(2):725-31. (PMID: 22247455)
Eur J Pharmacol. 2014 Sep 15;739:96-105. (PMID: 24291107)
Trends Cell Biol. 2007 May;17(5):230-8. (PMID: 17420126)
Subcell Biochem. 2007;45:323-35. (PMID: 18193642)
Science. 2002 Jan 18;295(5554):491-5. (PMID: 11799243)
Proc Natl Acad Sci U S A. 2015 Nov 3;112(44):13705-10. (PMID: 26483470)
J Biol Chem. 1998 Feb 27;273(9):5337-42. (PMID: 9478993)
Curr Opin Neurobiol. 2009 Jun;19(3):275-83. (PMID: 19497733)
Invest Ophthalmol Vis Sci. 2009 Feb;50(2):717-28. (PMID: 18952924)
J Neurochem. 2005 Jan;92(2):235-45. (PMID: 15663472)
Prog Neurobiol. 2007 Apr;81(5-6):272-93. (PMID: 17188796)
Cell. 2008 Apr 4;133(1):38-52. (PMID: 18394988)
Biochem Biophys Res Commun. 2011 Sep 16;413(1):116-21. (PMID: 21872572)
J Neurosci. 2012 Sep 12;32(37):12744-55. (PMID: 22972998)
J Neurosci. 2005 Mar 2;25(9):2245-54. (PMID: 15745950)
J Mol Neurosci. 2012 Mar;46(3):585-94. (PMID: 21932038)
Invest Ophthalmol Vis Sci. 2010 Feb;51(2):991-1001. (PMID: 19815726)
Ann Neurol. 1996 Nov;40(5):695-700. (PMID: 8957009)
Cell. 2000 Dec 8;103(6):945-56. (PMID: 11136979)
Trends Neurosci. 2008 Sep;31(9):454-63. (PMID: 18675468)
Neuron. 2000 Jul;27(1):121-31. (PMID: 10939336)
PLoS One. 2013;8(2):e56340. (PMID: 23457553)
Nat Rev Mol Cell Biol. 2005 Jun;6(6):462-75. (PMID: 15928710)
Lancet Neurol. 2007 Oct;6(10):933-8. (PMID: 17884683)
J Neurosci. 2011 May 11;31(19):7089-101. (PMID: 21562271)
J Neurochem. 2006 Jul;98(1):1-10. (PMID: 16805791)
J Am Soc Nephrol. 2003 Jan;14(1):28-36. (PMID: 12506135)
Neuron. 2008 Jul 31;59(2):190-4. (PMID: 18667147)
Nat Neurosci. 2009 Jan;12(1):15-20. (PMID: 19029886)

0 (Calcium Channels)
0 (Ephrins)
EC 2.7.10.1 (Receptors, Eph Family)

Date Created: 20171206 Date Completed: 20180718 Latest Revision: 20181113

20250114

PMC5783492

10.3892/mmr.2017.8162

29207174