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
N1 - Funding Information:
Supported in part by PHS Research Grants EY 02120 (Dr Quigley), EY 01765 (Core Facility Grant, Wilmer Institute), by the Glaucoma Research Foundation, San Francisco, CA, by the David Worthen Fellowship and by the Claire and Amedee Maratier Institute, Tel-Aviv University, Israel.
PY - 2005/5
Y1 - 2005/5
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 RGCs mm -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.
AB - 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 RGCs mm -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.
KW - Glaucoma
KW - JNK
KW - Optic nerve transection
KW - Retinal ganglion cells
KW - c-jun
UR - http://www.scopus.com/inward/record.url?scp=18044369837&partnerID=8YFLogxK
U2 - 10.1016/j.exer.2004.11.016
DO - 10.1016/j.exer.2004.11.016
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AN - SCOPUS:18044369837
SN - 0014-4835
VL - 80
SP - 663
EP - 670
JO - Experimental Eye Research
JF - Experimental Eye Research
IS - 5
ER -