Common therapeutic strategies for diabetic retinopathy and glaucoma

Current Drug Therapy

Volumn 2, Issue 3, 2007, Pages 224-232

  Oshitari, Toshiyuki ^a,b,c,d   Roy, Sayon ^c  

^a KIMITSU CHUO HOSPITAL   (Japan)

^b CHIBA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^c BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d Sannoh Medical Center   (Japan)

Author keywords

Antisense oligonucleotides; Diabetic retinopathy; Extracellular matrix; Glaucoma; Retinal ganglion cell death; Small interference RNA

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; CASPASE 3; CASPASE 9; COLLAGEN TYPE 4; CYTOCHROME C; FIBRONECTIN; LAMININ; PROTEIN BAX; PROTEIN BCL XL; PROTEIN P53; RNA; TUMOR NECROSIS FACTOR; VASCULOTROPIN;

ARTICLE; BASEMENT MEMBRANE; BLINDNESS; BLOOD RETINA BARRIER; BLOOD VESSEL PERMEABILITY; CELL DIFFERENTIATION; CELL PROLIFERATION; DEATH; DEPHOSPHORYLATION; DIABETIC PATIENT; DIABETIC RETINOPATHY; DISEASE COURSE; EXTRACELLULAR MATRIX; GENE THERAPY; GLAUCOMA; HUMAN; INCIDENCE; MEMBRANE PERMEABILITY; MITOCHONDRIAL MEMBRANE; NEUROPROTECTION; OPTIC NERVE DISEASE; OPTIC NERVE INJURY; PATHOGENESIS; PRIORITY JOURNAL; REPERFUSION INJURY; RETINA GANGLION CELL; RNA INTERFERENCE; VISUAL FIELD; VISUAL IMPAIRMENT;

EID: 41549114372     PISSN: 15748855     EISSN: 10657630     Source Type: Journal    
DOI: 10.2174/157488507781695685     Document Type: Article

References (126)

1. Danis RP, Ciulla TA, Criswell M, Pratt L. Anti-angiogenic therapy of proliferative diabetic retinopathy. Expert Opin Pharmacother 2001; 2: 395-407.
2. Lorenzi M, Gerhardinger C. Early cellular and molecular changes induced by diabetes in the retina. Diabetologia 2001; 44: 791-804.
3. Barber AJ, Lieth E, Khin SA, et al. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest 1998; 102: 783-91.
4. Takano M, Sango K, Horie H, et al. Diabetes alters neurite regeneration from mouse retinal explants in culture. Neurosci Lett 1999; 275: 175-8.
5. Asnaghi V, Gerhardinger C, Hoehn T, Adeboje A, Lorenzi M. A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes 2003; 52: 506-11.
6. Barber AJ. A new view of diabetic retinopathy: a neurodegenera-tive disease of the eye. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27: 283-90.
7. Martin PM, Roon P, Van Ells TK, Ganapathy V, Smith SB. Death of retinal neurons in streptozotocin-induced diabetic mice. Invest Ophthalmol Vis Sci 2004; 45: 3330-6.
8. Oshitari T, Roy S. Diabetes: a potential enhancer of retinal injury in rat retinas. Neurosci Lett 2005; 390: 25-30.
9. Oshitari T. Non-viral gene therapy for diabetic retinopathy. Drug Dev Res 2006; 67: 835-41.
10. Das A, Frank RN, Zhang NL, Samadani E. Increase in collagen type IV and laminin in galactose-induced retinal capillary basement membrane thickening-prevention by an aldose reductase inhibitor. Exp Eye Res 1990; 50: 269-80.
11. Osterby R. Basement membrane morphology in diabetes mellitus, in: Rifkin H.P., Porte D. Jr. (Eds.) Diabetes Mellitus: Theory and Practice. New York, Elsevier Science 1990; 220-33.
12. Stitt AW, Anderson HR, Gardiner TA, Archer DB. Diabetic retinopathy: quantitative variation in capillary basement membrane thickening in arterial or venous environments. Br J Ophthalmol 1994; 78: 133-7.
13. Roy S, Zhang K, Roth T, Vinogradov S, Kao RS, Kabanov A. Reduction of fibronectin expression by intravitreal administration of antisense oligonucleotides in rat retina. Nat Biotechnol 1999; 17: 476-9.
14. Roy S, Sato T, Paryani G, Kao R. Downregulation of fibronectin overexpression reduces basement membrane thickening and vascu-lar lesions in retinas of galactose-fed rats. Diabetes 2003; 52: 1229-34.
15. Oshitari T, Brown D, Roy S. SiRNA strategy against overexpression of extracellular matrix in diabetic retinopathy. Exp Eye Res 2005; 81: 32-7.
16. Oshitari T, Polewski P, Chadda M, Li AF, Sato T, Roy S. Effect of combined antisense oligonucleotides against high-glucose-and diabetes-induced overexpression of extracellular matrix components and increased vascular permeability. Diabetes 2006; 55: 86-92.
17. Levin LA. Pathophysiology of the progressive optic neuropathy of glaucoma. Ophthalmol Clin North Am 2005; 18: 355-64, v.
18. Quigley HA. New paradigms in the mechanisms and management of glaucoma. Eye 2005; 19: 1241-8.
19. Iwase A, Suzuki Y, Araie M, et al. Tajimi Study Group, Japan Glaucoma Society. The prevalence of primary open-angle glaucoma in Japanese: the Tajimi Study. Ophthalmology 2004; 111: 1641-8.
20. Quigley HA, Nickells RW, Kerrigan LA, Pease ME, Thibault DJ, Zack DJ. Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci 1995; 36: 774-86.
21. Nickells RW. Apoptosis of retinal ganglion cells in glaucoma: an update of the molecular pathways involved in cell death. Surv Ophthalmol 1999; 43: S151-61.
22. Kuehn MH, Fingert JH, Kwon YH. Retinal ganglion cell death in glaucoma: mechanisms and neuroprotective strategies. Ophthalmol Clin North Am 2005; 18: 383-95, vi.
23. Harris A, Rechtman E, Siesky B, Jonescu-Cuypers C, McCranor L, Garzozi HJ. The role of optic nerve blood flow in the pathogenesis of glaucoma. Ophthalmol Clin North Am 2005; 18: 345-53, v.
24. Morrison JC, Johnson EC, Cepurna W, Jia L. Understanding mechanisms of pressure-induced optic nerve damage. Prog Retin Eye Res 2005; 24: 217-40.
25. Floyd BB, Cleveland PH, Worthen DM. Fibronectin in human trabecular drainage channels. Invest Ophthalmol Vis Sci 1985; 26: 797-804.
26. Babizhayev MA, Brodskaya MW. Fibronectin detection in drainage outflow system of human eyes in ageing and progression of open-angle glaucoma. Mech Ageing Dev 1989; 47: 145-57.
27. Rodrigues MM, Katz SI, Foidart JM, Spaeth GL. Collagen, factor VIII antigen, and immunoglobulins in the human aqueous drainage channels. Ophthalmology 1980; 87: 337-45.
28. Rohen JW, Lutjen-Drecoll E, Flugel C, Meyer M, Grierson I. Ul-trastructure of the trabecular meshwork in untreated cases of primary open-angle glaucoma (POAG). Exp Eye Res 1993; 56: 683-92.
29. Li AF, Tane N, Roy S. Fibronectin overexpression inhibits trabecular meshwork cell monolayer permeability. Mol Vis 2004; 10: 750-7.
30. Tane N, Dhar S, Roy S, Pinheiro A, Ohira A, Roy S. Effect of excess synthesis of extracellular matrix components by trabecular meshwork cells: possible consequence on aqueous outflow. Exp Eye Res 2007; 84: 832-42.
31. Sato T, Roy S. Effect of high glucose on fibronectin expression and cell proliferation in trabecular meshwork cells. Invest Ophthalmol Vis Sci 2002; 43: 170-5.
32. Klein BE, Klein R, Jensen SC. Open-angle glaucoma and older-onset diabetes. The Beaver Dam Eye Study. Ophthalmology 1994; 101: 1173-7.
33. Dielemans I, de Jong PT, Stolk R, Vingerling JR, Grobbee DE, Hofman A. Primary open-angle glaucoma, intraocular pressure, and diabetes mellitus in the general elderly population. The Rotterdam Study. Ophthalmology 1996; 103: 1271-5.
34. Mitchell P, Smith W, Chey T, Healey PR. Open-angle glaucoma and diabetes: the Blue Mountains eye study, Australia. Ophthalmology 1997; 104: 712-8.
35. Bonovas S, Peponis V, Filiousso K. Diabetes mellitus as a risk factor for primary open-angle glaucoma: a meta-analysis. Diabet Med 2004; 21: 609-14.
36. Becker B. Diabetes mellitus and primary open-angle glaucoma. The XXVII Edward Jackson Memorial Lecture. Am J Ophthalmol 1971; 1: 1-16.
37. David R, Zangwill L, Stone D, Yassur Y. Epidemiology of intraocular pressure in a population screened for glaucoma. Br J Ophthalmol 1987; 71: 766-71.
38. Muranyi M, Fujioka M, He Q, et al. Diabetes activates cell death pathway after transient focal cerebral ischemia. Diabetes 2003; 52: 481-6.
39. Kanamori A, Nakamura M, Mukuno H, Maeda H, Negi A. Diabetes has an additive effect on neural apoptosis in rat retina with chronically elevated intraocular pressure. Curr Eye Res 2004; 28: 47-54.
40. Mandarino LJ, Sundarraj N, Finlayson J, Hassell HR. Regulation of fibronectin and laminin synthesis by retinal capillary endothelial cells and pericytes in vitro. Exp Eye Res 1993; 57: 609-21.
41. Tolentino MJ, Miller JW, Gragoudas ES, et al. Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate. Ophthalmology 1996; 103: 1820-8.
42. Amin RH, Frank RN, Kennedy A, Eliott D, Puklin JE, Abrams GW. Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 1997; 38: 36-47.
43. Boulton M, Foreman D, Williams G, McLeod D. VEGF localisation in diabetic retinopathy. Br J Ophthalmol 1998; 82: 561-8.
44. Joussen AM, Poulaki V, Mitsiades N, et al. Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression. FASEB J 2002; 16: 438-40.
45. Caldwell RB, Slapnick SM, McLaughlin BJ. Lanthanum and freeze-fracture studies of retinal pigment epithelial cell junctions in the streptozotocin diabetic rat. Curr Eye Res 1985; 4: 215-27.
46. Caldwell RB, Slapnick SM. Freeze-fracture and lanthanum studies of the retinal microvasculature in diabetic rats. Invest Ophthalmol Vis Sci 1992; 33: 1610-9.
47. Antonetti DA, Barber AJ, Khin S, Lieth E, Tarbell JM, Gardner TW. Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Penn State Retina Research Group. Diabetes 1998; 47: 1953-9.
48. Bill A. Editorial: The drainage of aqueous humor. Invest Ophthalmol 1975; 14: 1-3.
49. Yue BY. The extracellular matrix and its modulation in the trabecular meshwork. Surv Ophthalmol 1996; 40: 379-90.
50. Brown EJ. The role of extracellular matrix proteins in the control of phagocytosis. J Leukoc Biol 1986; 39: 579-91.
51. Esparza J, Vilardell C, Calvo J, et al. Fibronectin upregulates ge-latinase B (MMP-9) and induces coordinated expression of ge-latinase A (MMP-2) and its activator MT1-MMP (MMP-14) by human T lymphocyte cell lines. A process repressed through RAS/MAP kinase signaling pathways. Blood 1999; 94: 2754-66.
52. Haas TL, Madri JA. Extracellular matrix-driven matrix metallopro-teinase production in endothelial cells: implications for angiogene-sis. Trends Cardiovasc Med 1999; 9: 70-7.
53. Zhou L, Zhang SR, Yue BY. Adhesion of human trabecular meshwork cells to extracellular matrix proteins. Roles and distribution of integrin receptors. Invest Ophthalmol Vis Sci 1996; 37: 104-13.
54. Zhou L, Cheng EL, Rege P, Yue BY. Signal transduction mediated by adhesion of human trabecular meshwork cells to extracellular matrix. Exp Eye Res 2000; 70: 457-65.
55. Hocking DC, Sottile J, Langenbach KJ. Stimulation of integrin-mediated cell contractility by fibronectin polymerization. J Biol Chem 2000; 275:10673-82.
56. Smith-Thomas L, Richardson P, Parsons MA, Rennie IG, Benson M, MacNeil S. Additive effects of extra cellular matrix proteins and platelet derived mitogens on human retinal pigment epithelial cell proliferation and contraction. Curr Eye Res 1996; 15: 739-48.
57. Sato T, Paryani G, Kao RS, Li AF, Roy S. Antisense oligonucleotides modulate high glucose-induced laminin overexpression and cell proliferation: a potential for therapeutic application in diabetic microangiopathy. Antisense Nucleic Acid Drug Dev 2001; 11: 387-94.
58. Nagel KM, Holstad SG, Isenberg KE. Oligonucleotide pharmacotherapy: an antigene strategy. Pharmacotherapy 1993; 13: 177-88.
59. Stein CA, Cheng YC. Antisense oligonucleotides as therapeutic agents--is the bullet really magical? Science 1993; 261: 1004-12.
60. Chiang MY, Chan H, Zounes MA, Freier SM, Lima WF, Bennett CF. Antisense oligonucleotides inhibit intercellular adhesion molecule 1 expression by two distinct mechanisms. J Biol Chem 1991; 266: 18162-71.
61. Vickers T, Baker BF, Cook PD, et al. Inhibition of HIV-LTR gene expression by oligonucleotides targeted to the TAR element. Nucleic Acids Res 1991; 19: 3359-68.
62. Rohen JW. Why is intraocular pressure elevated in chronic simple glaucoma? Anatomical considerations. Ophthalmology 1983; 90: 758-65.
63. Kim KS, Lee BH, Kim IS. The measurement of fibronectin concentrations in human aqueous humor. Korean J Ophthalmol 1992; 6: 1-5.
64. Furuyoshi N, Furuyoshi M, Futa R, Gottanka J, Lutjen-Drecoll E. Ultrastructural changes in the trabecular meshwork of juvenile glaucoma. Ophthalmologica 1997; 211: 140-6.
65. Bradley JM, Vranka J, Colvis CM, et al. Effect of matrix metallo-proteinases activity on outflow in perfused human organ culture. Invest Ophthalmol Vis Sci 1998; 39: 2649-58.
66. Lutjen-Drecoll E, Wiendl H, Kaufman PL. Acute and chronic structural effects of pilocarpine on monkey outflow tissues. Trans Am Ophthalmol Soc 1998; 96: 171-91; discussion 192-5.
67. Kikuchi K, Miyabe Y, Hiraoka T, Takeda M. Incidence of glaucoma in people with diabetes mellitus screened at hospital. Folia Ophthalmol Jpn 2003; 54: 7-10 [Japanese].
68. Crooke ST. Antisense strategies. Curr Mol Med 2004; 4: 465-87.
69. Hammond SM, Bernstein E, Beach D, Hannon GJ. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 2000; 404: 293-6.
70. Billy E, Brondani V, Zhang H, Muller U, Filipowicz W. Specific interference with gene expression induced by long, double-stranded RNA in mouse embryonal teratocarcinoma cell lines. Proc Natl Acad Sci USA 2001; 98: 14428-33.
71. Nykänen A, Haley B, Zamore PD. ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell 2001; 107: 309-21.
72. Elbashir SM, Harborth J, Weber K, Tuschl T. Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods 2002; 26: 199-213.
73. Hutvágner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science 2002; 297: 2056-60.
74. Martinez J, Patkaniowska A, Urlaub H, Luhrmann R, Tuschl T. Single-stranded antisense siRNAs guide target RNA cleavage in RNAi. Cell 2002; 110: 563-74.
75. Mourelatos Z, Dostie J, Paushkin S, et al. miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev 2002; 16: 720-8.
76. Paddison PJ, Caudy AA, Bernstein E, Hannon GJ, Conklin DS. Short hairpin RNAs (shRNA) induce sequence-specific silencing in mammalian cells. Genes Dev 2002; 16: 948-58.
77. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 2001; 411: 494-8.
78. Oshitari T, Dezawa M, Okada S, et al. The role of c-fos in cell death and regeneration of retinal ganglion cells. Invest Ophthalmol Vis Sci 2002; 43: 2442-9.
79. Oshitari T, Fujimoto N, Adachi-Usami E. Citicoline has a protective effect on damaged retinal ganglion cells in mouse culture retina. Neuroreport 2002; 13: 2109-11.
80. Oshitari T, Okada S, Tokuhisa T, Adachi-Usami E. Adenovirus-mediated gene transfer of Bcl-xL impedes neurite regeneration in vitro. Neuroreport 2003; 14: 1159-62.
81. Oshitari T, Adachi-Usami E. The effect of caspase inhibitors and neurotrophic factors on damaged retinal ganglion cells. Neuroreport 2003; 14: 289-92.
82. Berkelaar M, Clarke DB, Wang YC, Bray GM, Aguayo AJ. Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats. J Neurosci 1994; 14: 4368-74.
83. Kuroiwa S, Katai N, Shibuki H, et al. Expression of cell cycle-related genes in dying cells in retinal ischemic injury. Invest Ophthalmol Vis Sci 1998; 39: 610-7.
84. Lam TT, Abler AS, Tso MO. Apoptosis and caspases after ische-mia-reperfusion injury in rat retina. Invest Ophthalmol Vis Sci 1999; 40: 967-75.
85. Garcia-Valenzuela E, Shareef S, Walsh J, Sharma SC. Programmed cell death of retinal ganglion cells during experimental glaucoma. Exp Eye Res 1995; 61: 33-44.
86. Isenmann S, Wahl C, Krajewski S, Reed JC, Bähr M. Upregulation of Bax protein in degenerating retinal ganglion cells precedes apoptotic cell death after optic nerve lesion in the rat. Eur J Neurosci 1997; 9: 1763-72.
87. Li Y, Schlamp CL, Poulsen KP, Nickells RW. Bax-dependent and independent pathways of retinal ganglion cell death induced by different damaging stimuli. Exp Eye Res 2000; 71: 209-13.
88. Levin LA, Schlamp CL, Spieldoch RL, Geszvain KM, Nickells RW. Identification of the bcl-2 family of genes in the rat retina. Invest Ophthalmol Vis Sci 1997; 38: 2545-53.
89. Shimizu S, Narita M, Tsujimoto Y. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature 1999; 399: 483-7.
90. Kermer P, Klöcker N, Labes M, Bähr M. Inhibition of CPP32-like proteases rescues axotomized retinal ganglion cells from secondary cell death in vivo. J Neurosci 1998; 18: 4656-62.
91. Krajewski S, Krajewska M, Ellerby LM, et al. Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia. Proc Natl Acad Sci U S A 1999; 96: 5752-7.
92. Kermer P, Ankerhold R, Klöcker N, Krajewski S, Reed JC, Bähr M. Caspase-9: involvement in secondary death of axotomized rat retinal ganglion cells in vivo. Brain Res Mol Brain Res 2000; 85: 144-50.
93. Tezel G, Li LY, Patil RV, Wax MB. TNF-α and TNF-α receptor-1 in the retina of normal and glaucomatous eyes. Invest Ophthalmol Vis Sci 2001; 42: 1787-94.
94. Tezel G, Yang X. Caspase-independent component of retinal ganglion cell death, in vitro. Invest Ophthalmol Vis Sci 2004; 45: 4049-59.
95. Diem R, Meyer R, Weishaupt JH, Bähr M. Reduction of potassium currents and phosphatidylinositol 3-kinase-dependent AKT phos-phorylation by tumor necrosis factor-(alpha) rescues axotomized retinal ganglion cells from retrograde cell death in vivo. J Neurosci 2001; 21: 2058-66.
96. Banasiak KJ, Xia Y, Haddad GG. Mechanisms underlying hy-poxia-induced neuronal apoptosis. Prog Neurobiol 2000; 62: 215-49.
97. Lam TT, Abler AS, Kwong JM, Tso MO. N-methyl-D-aspartate (NMDA)--induced apoptosis in rat retina. Invest Ophthalmol Vis Sci 1999; 40: 2391-7.
98. Awai M, Koga T, Inomata Y, et al. NMDA-induced retinal injury is mediated by an endoplasmic reticulum stress-related protein, CHOP/GADD153. J Neurochem 2006; 96: 43-52.
99. Tezel G. Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences. Prog Retin Eye Res 2006; 25: 490-513.
100. Yokoyama A, Oshitari T, Negishi H, Dezawa M, Mizota A, Adachi-Usami E. Protection of retinal ganglion cells from ischemia-reperfusion injury by electrically applied Hsp27. Invest Ophthalmol Vis Sci 2001; 42: 3283-6.
101. Mo X, Yokoyama A, Oshitari T, et al. Rescue of axotomized retinal ganglion cells by BDNF gene electroporation in adult rats. Invest Ophthalmol Vis Sci 2002; 43: 2401-5.
102. Otori Y, Shimada S, Morimura H, Ishimoto I, Tohyama M, Tano Y. Expression of c-fos and c-jun mRNA following transient retinal ischemia: an approach using ligation of the retinal central artery in the rat. Surv Ophthalmol 1997; 42: S96-104.
103. Levkovitch-Verbin H, Dardik R, Vander S, Nisgav Y, Kalev-Landoy M, Melamed S. Experimental glaucoma and optic nerve transection induce simultaneous upregulation of proapoptotic and prosurvival genes. Invest Ophthalmol Vis Sci 2006; 47: 2491-7.
104. Huang W, Dobberfuhl A, Filippopoulos T, et al. Transcriptional up-regulation and activation of initiating caspases in experimental glaucoma. Am J Pathol 2005; 167: 673-81.
105. Hanninen VA, Pantcheva MB, Freeman EE, Poulin NR, Grossk-reutz CL. Activation of caspase 9 in a rat model of experimental glaucoma. Curr Eye Res 2002; 25: 389-95.
106. Huang W, Fileta JB, Dobberfuhl A, et al. Calcineurin cleavage is triggered by elevated intraocular pressure, and calcineurin inhibition blocks retinal ganglion cell death in experimental glaucoma. Proc Natl Acad Sci U S A 2005; 102: 12242-7.
107. Dreyer EB. A proposed role for excitotoxicity in glaucoma. J Glaucoma 1998; 7: 62-7.
108. Honkanen RA, Baruah S, Zimmerman MB, et al. Vitreous amino acid concentrations in patients with glaucoma undergoing vitrec-tomy. Arch Ophthalmol 2003; 121: 183-8.
109. Levkovitch-Verbin H, Martin KR, Quigley HA, Baumrind LA, Pease ME, Valenta D. Measurement of amino acid levels in the vitreous humor of rats after chronic intraocular pressure elevation or optic nerve transection. J Glaucoma 2002; 11: 396-405.
110. Wamsley S, Gabelt BT, Dahl DB, et al. Vitreous glutamate concentration and axon loss in monkeys with experimental glaucoma. Arch Ophthalmol 2005; 123: 64-70.
111. Carter-Dawson L, Crawford ML, Harwerth RS, et al. Vitreal glutamate concentration in monkeys with experimental glaucoma. Invest Ophthalmol Vis Sci 2002; 43: 2633-7.
112. Podesta F, Romeo G, Liu WH, et al. Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro. Am J Pathol 2002; 156: 1025-32.
113. Kowluru RA, Abbas SN. Diabetes-induced mitochondrial dysfunction in the retina. Invest Ophthalmol Vis Sci 2003; 44: 5327-34.
114. Seki M, Tanaka T, Nawa H, et al. Involvement of brain-derived neurotrophic factor in early retinal neuropathy of streptozotocin-induced diabetes in rats: therapeutic potential of brain-derived neurotrophic factor for dopaminergic amacrine cells. Diabetes 2004; 53: 2412-9.
115. Aizu Y, Katayama H, Takahama S, Hu J, Nakagawa H, Oyanagi K. Topical instillation of ciliary neurotrophic factor inhibits retinal degeneration in streptozotocin-induced diabetic rats. Neuroreport 2003; 14; 2067-71.
116. Martin KR, Quigley HA, Zack DJ, et al. Gene therapy with brain-derived neurotrophic factor as a protection: retinal ganglion cells in a rat glaucoma model. Invest Ophthalmol Vis Sci 2003; 44: 4357-65.
117. Nakazawa T, Tamai M, Mori N. Brain-derived neurotrophic factor prevents axotomized retinal ganglion cell death through MAPK and PI3K signaling pathways. Invest Ophthalmol Vis Sci 2002; 43: 3319-26.
118. Bähr M. Live or let die-retinal ganglion cell death and survival during development and in the lesioned adult CNS. Trends Neurosci 2000; 23: 483-90.
119. Qin Q, Patil K, Sharma SC. The role of Bax-inhibiting peptide in retinal ganglion cell apoptosis after optic nerve transection. Neurosci Lett 2004; 372: 17-21.
120. Lingor P, Koeberle P, Kügler S, Bähr M. Down-regulation of apoptosis mediators by RNAi inhibits axotomy-induced retinal ganglion cell death in vivo. Brain 2005; 128(Pt 3): 550-8.
121. Isenmann S, Engel S, Gillardon F, Bähr M. Bax antisense oligonucleotides reduce axotomy-induced retinal ganglion cell death in vivo by reduction of Bax protein expression. Cell Death Differ 1999; 6: 673-82.
122. Koh JY, Gwag BJ, Lobner D, Choi DW. Potentiated necrosis of cultured cortical neurons by neurotrophins. Science 1995; 268: 573-5.
123. Hartmann A, Troadec JD, Hunot S, et al. Caspase-8 is an effector in apoptotic death of dopaminergic neurons in Parkinson's disease, but pathway inhibition results in neuronal necrosis. J Neurosci 2001; 21: 2247-55.
124. Vandenabeele P, Vanden Berghe T, Festjens N. Caspase inhibitors promote alternative cell death pathways. Sci STKE 2006; 358: 44.
125. Whitmore AV, Libby RT, John SW. Glaucoma: thinking in new ways-a role for autonomous axonal self-destruction and other com-partmentalised processes? Prog Retin Eye Res 2005; 24: 639-62.
126. Negishi H, Dezawa M, Oshitari T, Adachi-Usami E. Optic nerve regeneration within artificial Schwann cell graft in the adult rat. Brain Res Bul 2001; 55: 409-19.