期刊
BRAIN RESEARCH
卷 1057, 期 1-2, 页码 17-28出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2005.07.005
关键词
retinal degeneration; ganglion cell; apoptosis; Akt; glaucoma
Neuronal cells undergo apoptosis when deprived of neurotrophic factors due to injury, trauma, or neurodegenerative disease. This study examined cell death in the retina after chronic elevation of intraocular pressure (IOP) in an experimental rat model of human glaucomatous disease. Three episcleral veins on the ocular surface of rats were cauterized. Activation of several cell death programs represented by Fas ligand, FADD (Fas Associated Death Domain/Mortl) and the caspase cascade (caspase-8 and -3) and survival programs represented by phosphorylated protein kinase B (PKB/Akt), Bcl-2 associated death domain (BAD), and cAMP responsive element binding protein (CREB) were examined using immunohistochemistry and Western blotting. Following injury, two major events occurred simultaneously in the retina: activation of programmed cell death pathways and activation of survival mechanisms to maintain the cellular homeostasis of the retina. At the later stage of injury, markers of an activated cell death program appeared to be concentrated in the retinal ganglion cells. In conclusion, we suggest that endogenous cell survival factors triggered at the early stage of injury play a critical role in control of the death or survival of retinal ganglion cells and that the manipulation of this decision phase is one of the therapeutic targets for glaucoma. (c) 2005 Elsevier B.V. All rights reserved.
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