Abstract
The pathogenesis of photic retinopathy has been actively investigated for many years. Although the exact pathogenic mechanism involved in light-induced photoreceptor degeneration remains unknown, certain hypotheses were made based on previous animal studies [1-8]. Free radical formation and lipid peroxidation are among the most widely accepted hypotheses regarding the pathogenesis of photic retinopathy [1-5]. In addition, possible roles for protein synthesis and alteration of intracellular Ca2+ concentration in light-induced photoreceptor cell death have been suggested [6–8]. Protein synthesis inhibitors, such as cycloheximide and Ca2+ channel overload blockers, such as flunarizine, were both demonstrated to have ameliorative effects on retinal photic injury [6–8]. These findings provided supportive evidence of the possible involvement of protein synthesis and alteration of intracellular Ca2+ concentration in retinal photic injury. However, the mechanism whereby these two factors ameliorated light-induced photoreceptor cell death was not determined.
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References
Feeney L, Berman ER. Oxygen toxicity: membrane damage by free radicals. Invest Ophthalmol Vis Sci 1976; 15: 789–792.
Noell WK. Possible mechanisms of photoreceptor damage by light in mammalian eyes. Vision Res 1980; 20: 1163–1171.
Anderson RE, Rapp LM, Wiegand RD. Lipid peroxidation and retinal degeneration. Current Eye Res 1984; 3(1): 223–227.
Organisciak DT, Wang HM, Xie A, Reeves DS and Donoso LA. Intense-light mediated changes in rat rod outer segment lipids and proteins. Prog Clin Biol. Res 1989; 314: 493–512.
Tso MOM. Experiments on visual cells by nature and man: in search of treatment for photoreceptor degeneration. Invest Ophthalmol Vis Sci 1989; 30: 2430–2454.
Shahinfar S, Edward DP and Tso MOM. A pathologic study of photoreceptor cell death in retinal photic injury. Current Eye Res 1991; 10: 47–59.
Edward DP, Lam TT, Shahinfar S, Li J and Tso MOM. Amelioration of light-induced retinal degeneration by a calcium overload blocker flunarizine. Arch Ophthalmol 1991; 109: 554–562.
Li J, Edward DP, Lam TT, Tso MOM. Amelioration of retinal photic injury by a combination of flunarizine and dimethylthiourea. Exp Eye Res 1993; 56: 71–78.
Tomei LD, Cope FO. Apoptosis: the molecular basis of cell death. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 1991.
Compton MM. A biochemical hallmark of apoptosis: internucleosomal degeneration of the genome. Cancer Metastasis Rev 1992; 11: 105–119.
Deckwerth TL, Johnson EM Jr. Temporal analysis of events associated with programmed cell death (apoptosis) of neurons deprived of nerve growth factor. J Cell Biol. 1993; 123: 1207–1222.
Martin DP, Schmidt RE, DiStefano PS, Lowry OH, Carter JG, Johnson EMJ. Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation. J Cell Biol. 1988; 106: 829–844.
Oppenheim RW, Prevette D, Tytell M, Homma S. Naturally occurring and induced neuronal death in the chick embryo in vivo requires protein and RNA synthesis: evidence for the role of cell death genes. Dev Biol. 1990; 138: 104–113.
Ghibelli L, Nosseri C., Oliverio S, Piacentini M, Autuori F. Cycloheximide can rescue heat-shocked L cells from death by blocking stress-induced apoptosis. Exp Cell Res 1992; 201: 436–443.
Martin SJ. Protein or RNA synthesis inhibition induces apoptosis of mature human CD4+ T cell blasts. Immunol Lett 1993; 35: 125–134.
Inouye M, Tamaru M, Kameyama Y. Effects of cycloheximide and actinomycin D on radiation-induced apoptotic cell death in the developing mouse cerebellum. Int J Rad Biol. 1992; 61: 669–674.
Wyllie, AH, Morris RG, Smith AL, Dunlop D. Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol 1984; 142: 67–77.
Cohen JJ, Duke RC. Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death. J Immunol 1984; 132: 38–42.
Johnson EM Jr, Deckwerth T. Molecular mechanisms of developmental neuronal death. Annu Rev Neurosci 1993; 16: 31–46.
Jones DP, McCondey DJ, Nicotera P, Orrenius S. Calcium-activated DNA fragmentation in rat liver nuclei. J Biol. Chem 1989; 264: 6398–6403.
Duke RC, Chervenak R, Cohen JJ. Endogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis. Proc Natl Acad Sci USA 1983; 80: 6361–6365.
McConkey DJ, Hartzeil P, Duddy SK, Hakansson H, Orrenius S. 2,3,7,8 tetrachlorodibenzo-p-dioxin kills immature thymocytes by Ca2+-mediated endonuclease activation. Science 1988; 242: 256–259.
McConkey DJ, Nicotera P, Hartzell P, Bellomo G, Wyllie AH, Orrenius S. Glucocorticoid activate a suicide process in thymocytes through an elevation of cytosolic Ca2+ concentration. Arch Biochem Biophys 1989; 269: 365–370.
McConkey DJ, Orrenius S, Fondai M. Cellular signaling in programmed cell death (apoptosis). Immunol Today 1990; 11: 120–121.
McConkey DJ, Jondal M, Orrenius S. Cellular signaling in thymocyte apoptosis. Semin Immunol 1992; 4: 371–377.
Collins RJ, Harmon BV, Souvlis T, Pope JH, Kerr JF. Effects of cycloheximide on B-chronic lymphocytic leukaemic and normal lymphocytes in vitro: induction of apoptosis. Br J Cancer 1991; 64: 518–522.
Belloma G, Perotti M, Taddei F et al. Tumor necrosis factor alpha induces apoptosis in mammary adenocarcinoma cells by an increase in intranuclear free Ca2+ concentration and DNA fragmentation. Cancer Res 1992; 52: 1342–1346.
Chang GQ, Hao Y, Wong F. Apoptosis: Final common pathway of photoreceptor death in rd, rds and rhodopsin mutant mice. Neuron. 1993; 11: 595–605.
Tso MOM, Zhang C., Abler AS, et al. Apoptosis leads to photoreceptor degeneration in inherited retinal dystrophy of RCS rats. Invest Ophthalmol Vis Sci 1994; 2693–2699.
Rich KM, Hollowell JP. Flunarizine protects neurons from death after axotomy or NGF deprivation. Science 1990; 248: 1419–1421.
Gavriela Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA. J Cell Biol. 1992; 119: 493–501.
Tilly JL, Hsueh AJ. Microscale autoradiographic method for the qualitative and quantitative analysis of apoptotic DNA fragmentation. J Cell Physiol 1993; 153(3): 519–526.
Umansky SR. Apoptotic process in the radiation-induced death of lymphocytes, in Tomei LD, Cope FO, eds. Apoptosis: The molecular basis of cell death. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press 1991: 193–208.
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Li, S., Chang, CJ., Abler, A.S., Tso, M.O.M. (1995). Inhibitory Effects of Cycloheximide and Flunarizine on Light-Induced Apoptosis of Photoreceptor Cells. In: Anderson, R.E., LaVail, M.M., Hollyfield, J.G. (eds) Degenerative Diseases of the Retina. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1897-6_4
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DOI: https://doi.org/10.1007/978-1-4615-1897-6_4
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