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S. Melamed, R. Dardik, S. Valder, Y. Nisgav, H. Levkovitch–Verbin; The Mechanism of Retinal Ganglion Cell Death in Experimental Glaucoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1247.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the pathogenesis of retinal ganglion cell (RGC) damage in experimental glaucoma using the translimbal photocoagulation laser model.
Experimental glaucoma was induced unilaterally in 58 Wistar rats. All eyes developed elevated intraocular pressure. The involvement of caspase–3, Bcl–2, p–AKT and members of the MAP kinase pathway was evaluated by immunohistochemistry, western blotting and RT–PCR.
Protein levels of the protease caspase–3 were elevated from day1 to day 64(p<0.05) returning to baseline on day 90. No change was observed in the mRNA levels of caspase–3. On day 8, a significant down–regulation of the pro–survival gene Bcl–2 was observed by 2 fold. However, mRNA levels of Bax gene were unchanged. Significant increase (1.5 fold; p< 0.05) in the level of the pro–survival protein p–Akt, a member of the PI3–kinase survival pathway, was detected on day 1 following IOP elevation, returning to baseline on day 8 and remaining unchanged up to 90 days. A significant increase of the pro–apoptotic MAP kinase p–ERK was detected by western blotting early after the induction of elevated IOP(1.35 fold; p< 0.05) on day 1, returning to normal on day 8. Using immunohistochemistry, a significant 10 fold increase in p–ERK level on day 2 was detected. Significant immunolabeling for p–SAPK/ JNK began on day 8, reaching a 6–fold significant elevation by day 30 (p<0.05).
RGC death in glaucoma involves activation of multiple apoptotic pathways on different time points including the MAP kinase pathway, the PI3–kinase survival pathway, the Bcl–2 gene and the caspase family.
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