TY - JOUR
T1 - Regulation of cell death and survival pathways in experimental glaucoma
AU - Levkovitch-Verbin, Hani
AU - Harizman, Noga
AU - Dardik, Rima
AU - Nisgav, Yael
AU - Vander, Shelly
AU - Melamed, Shlomo
PY - 2007/8
Y1 - 2007/8
N2 - This study investigates cell death and survival pathways in experimental glaucoma using the translimbal photocoagulation laser model. Glaucoma was induced unilaterally in 79 Wistar rats and all eyes developed elevated intraocular pressure. The involvement of caspase-3, p-AKT and members of the MAP kinase pathway was evaluated by immunohistochemistry and Western blotting. We found that protein levels of caspase-3 were elevated from day 15 to day 30 (p < 0.05). All investigated members of the MAP kinase pathway were significantly activated. P-SAPK/JNK activation began on day 2, reaching a 6-fold elevation by day 30 (p < 0.05). The p-P38 level was elevated on days 2 and 8 (p < 0.05), followed by a decrease to baseline on day 15. The level of p-ATF-2, the substrate of P38, was significantly elevated at all time points tested, up to day 30 (p < 0.05). P-ERK was detected early (p < 0.05) on day 1, returning to normal on day 15. The pro-survival protein p-Akt, a member of the PI3-kinase survival pathway, was also detected early on day 1 (p < 0.05) returning to baseline on day 8 and remaining unchanged up to 64 days. We conclude that retinal ganglion cell death in glaucoma involves activation, at different time points, of multiple pro-apoptotic pathways (the MAP kinase pathway and the caspase family) and pro-survival (PI-3 Kinase/ Akt and p-ERK).
AB - This study investigates cell death and survival pathways in experimental glaucoma using the translimbal photocoagulation laser model. Glaucoma was induced unilaterally in 79 Wistar rats and all eyes developed elevated intraocular pressure. The involvement of caspase-3, p-AKT and members of the MAP kinase pathway was evaluated by immunohistochemistry and Western blotting. We found that protein levels of caspase-3 were elevated from day 15 to day 30 (p < 0.05). All investigated members of the MAP kinase pathway were significantly activated. P-SAPK/JNK activation began on day 2, reaching a 6-fold elevation by day 30 (p < 0.05). The p-P38 level was elevated on days 2 and 8 (p < 0.05), followed by a decrease to baseline on day 15. The level of p-ATF-2, the substrate of P38, was significantly elevated at all time points tested, up to day 30 (p < 0.05). P-ERK was detected early (p < 0.05) on day 1, returning to normal on day 15. The pro-survival protein p-Akt, a member of the PI3-kinase survival pathway, was also detected early on day 1 (p < 0.05) returning to baseline on day 8 and remaining unchanged up to 64 days. We conclude that retinal ganglion cell death in glaucoma involves activation, at different time points, of multiple pro-apoptotic pathways (the MAP kinase pathway and the caspase family) and pro-survival (PI-3 Kinase/ Akt and p-ERK).
KW - MAP kinase
KW - glaucoma
KW - p-Akt
KW - retinal ganglion cells
UR - http://www.scopus.com/inward/record.url?scp=34547096278&partnerID=8YFLogxK
U2 - 10.1016/j.exer.2007.04.011
DO - 10.1016/j.exer.2007.04.011
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AN - SCOPUS:34547096278
SN - 0014-4835
VL - 85
SP - 250
EP - 258
JO - Experimental Eye Research
JF - Experimental Eye Research
IS - 2
ER -