Retinal ganglion cell death is delayed by activation of retinal intrinsic cell survival program.
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/Mort1) 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.
Kim
Hwa Sun
HS
Department of Ophthalmology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-701, South Korea.
Park
Chan Kee
CK
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western / Q000379:methods; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D005786:Gene Expression Regulation / Q000502:physiology*; D005901:Glaucoma / Q000378:metabolism / Q000503:physiopathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007429:Intraocular Pressure; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011726:Pyridinium Compounds / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D013266:Stilbamidines / Q000378:metabolism; D013997:Time Factors; D048069:Tumor Necrosis Factors / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D048868:Adaptor Proteins, Signal Transducing; D017362:Cyclic AMP Response Element-Binding Protein; C505533:FADD protein, human; C505661:FASLG protein, human; C505535:Fadd protein, rat; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; C505662:Faslg protein, rat; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D011726:Pyridinium Compounds; D013266:Stilbamidines; D048069:Tumor Necrosis Factors; D051025:bcl-Associated Death Protein; C076868:4-(4-dihexadecylaminostyryl)-N-methylpyridium; D051058:Oncogene Protein v-akt; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases