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The transcription factor c-jun is activated in retinal ganglion cells in experimental rat glaucoma.
Exp Eye Res. 2005 May; 80(5):663-70.EE

Abstract

This study investigates the role of the MAP kinase pathway including c-jun, ATF-2 and JNK in glaucomatous eyes of rats and in optic nerve transection. Glaucoma was induced in one eye of 51 adult Wistar rats by laser treatment to the trabecular meshwork. Eighteen further rats underwent unilateral optic nerve transection. We studied the transcription factor c-jun, its activated form, phospho-c-jun, the transcription factor p-ATF-2, and the enzyme JNK by immunohistochemistry. The activation of p-c-jun was also investigated using western blot analysis. Treated and control eyes were compared in a masked way at multiple time points after injury. We found a statistically significant increase in immunolabelling for c-jun and phospho-c-jun in retinal ganglion cells (RGCs) from 1 day to 4 weeks after intraocular pressure (IOP) elevation. At 1 and 2 days after the laser treatment, a mean of 2.9+/-3.3 RGCsmm(-1) were positive for c-jun (n=12, p=0.005, t-test), increasing to a mean of 13.4+/-7.5 cells mm(-1) at 1 week (n=18, p=0.00005), and decreasing to 2.3+/-2.0 cells mm(-1) at 2 weeks (n=5, p=0.04) and 0.1+/-0.1 cells mm(-1) at 2 months. Few of the 47 control eyes had any labelling for c-jun or phospho-c-jun, while between 80 and 100% of elevated IOP eyes showed positivity during the first 2 weeks of experimental glaucoma. After optic nerve transection, c-jun and phospho-c-jun were also significantly activated at 1, 2 and 9 days (p<0.03, t-test). Western blot analysis demonstrated significantly increased phospho-c-jun amounts in both transected and glaucomatous eyes compared to control fellow eyes 1 week following treatment. JNK was not significantly activated in glaucoma or optic nerve transection. P-ATF-2 was not significantly activated in glaucoma, but was significantly increased 2 days after optic nerve transection. We conclude that the process leading to RGC death in experimental glaucoma and after optic nerve transection involves the activation of c-jun at the RGC layer. C-jun is activated more gradually in glaucoma then after optic nerve transection.

Authors+Show Affiliations

Levkovitch-Verbin H
Sam Rothberg Molecular Biology Lab, Goldschleger Eye Institute, Sheba Medical Center, Tel-Aviv University, Tel-Hashomer 52621, Israel. halevko@hotmail.com
Quigley HA
No affiliation info available
Martin KR
No affiliation info available
Harizman N
No affiliation info available
Valenta DF
No affiliation info available
Pease ME
No affiliation info available
Melamed S
No affiliation info available

MeSH

Activating Transcription Factor 2AnimalsAxotomyBlotting, WesternCyclic AMP Response Element-Binding ProteinGlaucomaImmunohistochemistryJNK Mitogen-Activated Protein KinasesLasersMAP Kinase Kinase 4Mitogen-Activated Protein Kinase KinasesModels, AnimalOptic NerveOptic Nerve InjuriesPhosphorylationProto-Oncogene Proteins c-junRatsRats, WistarRetinal Ganglion CellsTrabeculectomyTranscription Factors

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15862173

Citation

Levkovitch-Verbin, Hana, et al. "The Transcription Factor C-jun Is Activated in Retinal Ganglion Cells in Experimental Rat Glaucoma." Experimental Eye Research, vol. 80, no. 5, 2005, pp. 663-70.
Levkovitch-Verbin H, Quigley HA, Martin KR, et al. The transcription factor c-jun is activated in retinal ganglion cells in experimental rat glaucoma. Exp Eye Res. 2005;80(5):663-70.
Levkovitch-Verbin, H., Quigley, H. A., Martin, K. R., Harizman, N., Valenta, D. F., Pease, M. E., & Melamed, S. (2005). The transcription factor c-jun is activated in retinal ganglion cells in experimental rat glaucoma. Experimental Eye Research, 80(5), 663-70.
Levkovitch-Verbin H, et al. The Transcription Factor C-jun Is Activated in Retinal Ganglion Cells in Experimental Rat Glaucoma. Exp Eye Res. 2005;80(5):663-70. PubMed PMID: 15862173.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The transcription factor c-jun is activated in retinal ganglion cells in experimental rat glaucoma. AU - Levkovitch-Verbin,Hana, AU - Quigley,Harry A, AU - Martin,Keith R G, AU - Harizman,Noga, AU - Valenta,Danielle F, AU - Pease,Mary Ellen, AU - Melamed,Shlomo, Y1 - 2005/01/04/ PY - 2004/05/18/received PY - 2004/11/07/revised PY - 2004/11/29/accepted PY - 2005/5/3/pubmed PY - 2005/9/2/medline PY - 2005/5/3/entrez SP - 663 EP - 70 JF - Experimental eye research JO - Exp Eye Res VL - 80 IS - 5 N2 - This study investigates the role of the MAP kinase pathway including c-jun, ATF-2 and JNK in glaucomatous eyes of rats and in optic nerve transection. Glaucoma was induced in one eye of 51 adult Wistar rats by laser treatment to the trabecular meshwork. Eighteen further rats underwent unilateral optic nerve transection. We studied the transcription factor c-jun, its activated form, phospho-c-jun, the transcription factor p-ATF-2, and the enzyme JNK by immunohistochemistry. The activation of p-c-jun was also investigated using western blot analysis. Treated and control eyes were compared in a masked way at multiple time points after injury. We found a statistically significant increase in immunolabelling for c-jun and phospho-c-jun in retinal ganglion cells (RGCs) from 1 day to 4 weeks after intraocular pressure (IOP) elevation. At 1 and 2 days after the laser treatment, a mean of 2.9+/-3.3 RGCsmm(-1) were positive for c-jun (n=12, p=0.005, t-test), increasing to a mean of 13.4+/-7.5 cells mm(-1) at 1 week (n=18, p=0.00005), and decreasing to 2.3+/-2.0 cells mm(-1) at 2 weeks (n=5, p=0.04) and 0.1+/-0.1 cells mm(-1) at 2 months. Few of the 47 control eyes had any labelling for c-jun or phospho-c-jun, while between 80 and 100% of elevated IOP eyes showed positivity during the first 2 weeks of experimental glaucoma. After optic nerve transection, c-jun and phospho-c-jun were also significantly activated at 1, 2 and 9 days (p<0.03, t-test). Western blot analysis demonstrated significantly increased phospho-c-jun amounts in both transected and glaucomatous eyes compared to control fellow eyes 1 week following treatment. JNK was not significantly activated in glaucoma or optic nerve transection. P-ATF-2 was not significantly activated in glaucoma, but was significantly increased 2 days after optic nerve transection. We conclude that the process leading to RGC death in experimental glaucoma and after optic nerve transection involves the activation of c-jun at the RGC layer. C-jun is activated more gradually in glaucoma then after optic nerve transection. SN - 0014-4835 UR - https://www.unboundmedicine.com/medline/citation/15862173/The_transcription_factor_c_jun_is_activated_in_retinal_ganglion_cells_in_experimental_rat_glaucoma_ DB - PRIME DP - Unbound Medicine ER -