title: Novel neuroprotective strategies in ischemic retinal lesions.
abstract: Retinal ischemia can be effectively modeled by permanent bilateral common carotid artery occlusion, which leads to chronic hypoperfusion-induced degeneration in the entire rat retina. The complex pathways leading to retinal cell death offer a complex approach of neuroprotective strategies. In the present review we summarize recent findings with different neuroprotective candidate molecules. We describe the protective effects of intravitreal treatment with: (i) urocortin 2; (ii) a mitochondrial ATP-sensitive K(+) channel opener, diazoxide; (iii) a neurotrophic factor, pituitary adenylate cyclase activating polypeptide; and (iv) a novel poly(ADP-ribose) polymerase inhibitor (HO3089). The retinoprotective effects are demonstrated with morphological description and effects on apoptotic pathways using molecular biological techniques.
authors.affiliation: Department of Experimental Zoology and Neurobiology, University of Pecs, H-7624 Pecs, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Szabadfi
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pecs, H-7624 Pecs, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Mester
authors.affiliation: Department of Anatomy, University of Pecs, H-7624 Pecs, Hungary.
authors.forename: Dora
authors.initials: D
authors.lastname: Reglodi
authors.affiliation: Department of Anatomy, University of Pecs, H-7624 Pecs, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Kiss
authors.affiliation: Department of Experimental Zoology and Neurobiology, University of Pecs, H-7624 Pecs, Hungary.
authors.forename: Norbert
authors.initials: N
authors.lastname: Babai
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pecs, H-7624 Pecs, Hungary.
authors.forename: Boglarka
authors.initials: B
authors.lastname: Racz
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pecs, H-7624 Pecs, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Kovacs
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pecs, H-7624 Pecs, Hungary.
authors.forename: Aliz
authors.initials: A
authors.lastname: Szabo
authors.affiliation: Department of Anatomy, University of Pecs, H-7624 Pecs, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tamas
authors.affiliation: Department of Experimental Zoology and Neurobiology, University of Pecs, H-7624 Pecs, Hungary.
authors.forename: Robert
authors.initials: R
authors.lastname: Gabriel
authors.affiliation: Department of Experimental Zoology and Neurobiology, University of Pecs, H-7624 Pecs, Hungary.|Department of Sportbiology, University of Pecs, H-7624 Pecs, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Atlasz
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use; D003981:Diazoxide / Q000627:therapeutic use; D004195:Disease Models, Animal; D007511:Ischemia / Q000188:drug therapy / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000627:therapeutic use; D015356:Retinal Artery Occlusion / Q000188:drug therapy* / Q000473:pathology; D054832:Urocortins / Q000627:therapeutic use
chemical_list: D001562:Benzimidazoles; C508983:HO 3089; D018696:Neuroprotective Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D054832:Urocortins; D003981:Diazoxide
references.citation: Invest Ophthalmol Vis Sci. 2008 Nov;49(11):4971-81
references.pmid: 18566458
references.citation: Exp Eye Res. 2006 Mar;82(3):488-95
references.pmid: 16168987
references.citation: Dev Neurosci. 2002;24(1):14-23
references.pmid: 12145407
references.citation: Acta Ophthalmol. 2009 Jun;87(4):362-7
references.pmid: 19416114
references.citation: Eur J Ophthalmol. 2003 Jan-Feb;13(1):80-5
references.pmid: 12635679
references.citation: Prog Neurobiol. 2008 Feb;84(2):148-56
references.pmid: 18078706
references.citation: Graefes Arch Clin Exp Ophthalmol. 2004 Mar;242(3):240-4
references.pmid: 14770318
references.citation: Ann N Y Acad Sci. 1999 Jun 30;874:27-37
references.pmid: 10415518
references.citation: FEBS Lett. 2005 Aug 15;579(20):4259-64
references.pmid: 16054139
references.citation: Gen Comp Endocrinol. 2007 Aug-Sep;153(1-3):108-14
references.pmid: 17289046
references.citation: Invest Ophthalmol Vis Sci. 2002 Feb;43(2):528-36
references.pmid: 11818401
references.citation: Neuropharmacology. 2003 Oct;45(5):623-36
references.pmid: 12941376
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2000 Jul;362(1):74-81
references.pmid: 10935536
references.citation: J Neurochem. 2003 Nov;87(4):969-80
references.pmid: 14622127
references.citation: Graefes Arch Clin Exp Ophthalmol. 2006 Feb;244(2):199-204
references.pmid: 15983810
references.citation: Invest Ophthalmol Vis Sci. 1998 Apr;39(5):777-85
references.pmid: 9538885
references.citation: Brain Res Dev Brain Res. 1990 Feb 1;51(2):185-94
references.pmid: 2323027
references.citation: Neurosci Lett. 2009 May 8;455(1):42-5
references.pmid: 19429103
references.citation: Brain Res. 2001 Jan 26;890(1):118-29
references.pmid: 11164774
references.citation: J Mol Neurosci. 2008 Nov;36(1-3):16-25
references.pmid: 18483879
references.citation: Invest Ophthalmol Vis Sci. 2006 May;47(5):2114-24
references.pmid: 16639023
references.citation: J Cereb Blood Flow Metab. 2006 May;26(5):684-95
references.pmid: 16177811
references.citation: Vis Neurosci. 1991 Apr;6(4):383-91
references.pmid: 2059572
references.citation: Invest Ophthalmol Vis Sci. 2003 Mar;44(3):1299-304
references.pmid: 12601062
references.citation: Ann N Y Acad Sci. 2009 Apr;1163:348-52
references.pmid: 19456357
references.citation: Endocrinology. 2004 Jan;145(1):24-35; discussion 21-3
references.pmid: 12970163
references.citation: Compr Ophthalmol Update. 2007 Jan-Feb;8(1):17-28
references.pmid: 17394756
references.citation: Prog Retin Eye Res. 2008 May;27(3):284-330
references.pmid: 18448380
references.citation: Vision Res. 1993 Mar;33(4):429-36
references.pmid: 8099245
references.citation: Trends Pharmacol Sci. 2004 May;25(5):259-64
references.pmid: 15120492
references.citation: Brain Res Bull. 1984 May;12(5):539-42
references.pmid: 6380651
references.citation: Neuropharmacology. 2000 Jun 8;39(8):1368-76
references.pmid: 10818253
references.citation: Prog Brain Res. 2008;173:583-90
references.pmid: 18929136
references.citation: Exp Eye Res. 2009 Mar;88(3):361-6
references.pmid: 19101544
references.citation: J Biol Chem. 2002 May 3;277(18):16075-80
references.pmid: 11847214
references.citation: Brain Res Rev. 2007 Apr;54(1):162-80
references.pmid: 17296232
references.citation: Eur J Pharmacol. 1994 Dec 27;271(2-3):489-95
references.pmid: 7705449
references.citation: Stroke. 1999 Dec;30(12):2713-8; discussion 2718-9
references.pmid: 10583002
references.citation: Brain Res. 1999 Aug 21;839(1):66-73
references.pmid: 10482800
references.citation: Ann N Y Acad Sci. 2006 Jul;1070:531-4
references.pmid: 16888220
references.citation: Ophthalmologe. 2010 Apr;107(4):347-53
references.pmid: 19787355
references.citation: Biochem Pharmacol. 2003 Apr 15;65(8):1373-82
references.pmid: 12694878
references.citation: Ann N Y Acad Sci. 2006 Jul;1070:507-11
references.pmid: 16891269
references.citation: Mol Endocrinol. 2005 Feb;19(2):441-58
references.pmid: 15514029
references.citation: Invest Ophthalmol Vis Sci. 2009 Feb;50(2):836-43
references.pmid: 18936152
references.citation: Science. 2002 Jul 12;297(5579):259-63
references.pmid: 12114629
references.citation: Invest Ophthalmol Vis Sci. 1994 Mar;35(3):907-15
references.pmid: 8125754
references.citation: Free Radic Biol Med. 2008 Apr 1;44(7):1286-94
references.pmid: 18082149
references.citation: Curr Pharm Des. 2004;10(23):2861-89
references.pmid: 15379674
references.citation: Prog Retin Eye Res. 2008 Nov;27(6):622-47
references.pmid: 18940262
references.citation: Brain Res. 2005 Jul 27;1051(1-2):72-80
references.pmid: 16004973
references.citation: Exp Eye Res. 2009 May;88(5):974-82
references.pmid: 19166832
references.citation: Toxicol Lett. 2003 Apr 4;139(2-3):153-62
references.pmid: 12628750
references.citation: Ann Thorac Surg. 2001 Dec;72(6):1849-54
references.pmid: 11789759
references.citation: Neuroscience. 2008 Aug 26;155(3):937-47
references.pmid: 18640247
references.citation: J Neurosci. 2002 Jan 15;22(2):404-12
references.pmid: 11784785
references.citation: Neurotox Res. 2009 Jul;16(1):68-76
references.pmid: 19526300
references.citation: Brain Res. 2004 Sep 3;1019(1-2):97-104
references.pmid: 15306243
references.citation: Neurotox Res. 2007 Sep;12(2):105-11
references.pmid: 17967734
references.citation: J Neurochem. 2009 Oct;111(2):488-98
references.pmid: 19682205
references.citation: J Neurochem. 2006 Sep;98(6):1732-45
references.pmid: 16903875
references.citation: Prog Retin Eye Res. 2004 Jan;23(1):91-147
references.pmid: 14766318
references.citation: Am J Ophthalmol. 1984 Feb;97(2):168-72
references.pmid: 6421164
references.citation: Am J Physiol Heart Circ Physiol. 2002 Sep;283(3):H1005-11
references.pmid: 12181130
references.citation: Neurosci Lett. 2004 Nov 30;372(1-2):110-3
references.pmid: 15531098
references.citation: Regul Pept. 2002 Nov 15;109(1-3):71-4
references.pmid: 12409217
references.citation: Neurosci Lett. 2005 Oct 28;387(3):168-72
references.pmid: 16026930
references.citation: Graefes Arch Clin Exp Ophthalmol. 2006 May;244(5):627-33
references.pmid: 16205934
references.citation: Invest Ophthalmol Vis Sci. 2003 Mar;44(3):1237-44
references.pmid: 12601054
references.citation: Brain Res. 2005 Oct 26;1060(1-2):73-80
references.pmid: 16202986
references.citation: Pharmacol Rev. 2009 Sep;61(3):283-357
references.pmid: 19805477
references.citation: Biochem Biophys Res Commun. 2005 Oct 28;336(3):731-6
references.pmid: 16061206
references.citation: Neurotox Res. 2005 Nov;8(3-4):227-33
references.pmid: 16371317
references.citation: Brain Res Bull. 2010 Mar 16;81(4-5):497-504
references.pmid: 19751807
references.citation: Cell Death Differ. 2001 Aug;8(8):801-7
references.pmid: 11526433
references.citation: Exp Eye Res. 2006 May;82(5):767-79
references.pmid: 16359664
references.citation: Brain Res Bull. 2005 Jul 30;66(2):85-90
references.pmid: 15982523
references.citation: Pharmacol Rev. 2002 Sep;54(3):375-429
references.pmid: 12223530
references.citation: Anesthesiology. 2009 Apr;110(4):774-80
references.pmid: 19322943
references.citation: Retina. 2008 Mar;28(3):511-7
references.pmid: 18327147
references.citation: Am J Pathol. 2003 Nov;163(5):1997-2008
references.pmid: 14578199
references.citation: Brain Res Dev Brain Res. 1990 May 1;53(2):194-9
references.pmid: 2357792
references.citation: Am J Pathol. 2007 Jul;171(1):53-67
references.pmid: 17591953
references.citation: Ann N Y Acad Sci. 2006 Jul;1070:149-55
references.pmid: 16888157
references.citation: Brain Res. 2006 May 4;1087(1):168-74
references.pmid: 16624259
references.citation: Neurosci Lett. 2005 Jan 20;373(3):195-9
references.pmid: 15619542
references.citation: Stroke. 2002 Apr;33(4):1107-12
references.pmid: 11935068
references.citation: Tohoku J Exp Med. 1999 Mar;187(3):227-36
references.pmid: 10458479
references.citation: Vision Res. 1999 Dec;39(24):3995-4002
references.pmid: 10748932
references.citation: Brain Res. 2004 Jul 23;1015(1-2):154-60
references.pmid: 15223379
references.citation: Neurobiol Dis. 2009 Jun;34(3):535-44
references.pmid: 19344761
references.citation: Brain Res Brain Res Rev. 2004 Nov;46(3):282-94
references.pmid: 15571770
references.citation: J Neuropathol Exp Neurol. 2003 Apr;62(4):329-39
references.pmid: 12722825
references.citation: J Endocrinol. 2007 Apr;193(1):157-69
references.pmid: 17400813
references.citation: Regul Pept. 2000 Sep 25;93(1-3):85-92
references.pmid: 11033056
references.citation: J Neurosci. 2007 Sep 19;27(38):10311-9
references.pmid: 17881537
references.citation: BMC Neurosci. 2009 May 27;10:52
references.pmid: 19473529
references.citation: Neurosci Lett. 1992 Sep 14;144(1-2):124-6
references.pmid: 1436691
references.citation: Exp Eye Res. 2008 Feb;86(2):366-74
references.pmid: 18160067
references.citation: Front Neuroendocrinol. 2007 Apr;28(1):1-27
references.pmid: 17083971
references.citation: Retina. 2009 Feb;29(2):262-8
references.pmid: 18854781
references.citation: Surv Ophthalmol. 1999 Jun;43 Suppl 1:S102-28
references.pmid: 10416754
references.citation: Exp Eye Res. 2003 Apr;76(4):505-16
references.pmid: 12634114
references.citation: Cardiovasc Res. 2003 Jul 1;59(1):1-6
references.pmid: 12829170
references.citation: Neurotox Res. 2000;2(2-3):215-27
references.pmid: 16787842
references.citation: J Comp Neurol. 1989 Feb 15;280(3):424-35
references.pmid: 2783937
references.citation: Invest Ophthalmol Vis Sci. 2010 Apr;51(4):2197-207
references.pmid: 19875663
references.citation: Brain Res. 2004 May 22;1008(2):252-60
references.pmid: 15145763
references.citation: Prog Retin Eye Res. 2009 Jan;28(1):63-86
references.pmid: 19070679
references.citation: J Mol Neurosci. 2008 Nov;36(1-3):57-60
references.pmid: 18642101
references.citation: Doc Ophthalmol. 2003 Jan;106(1):51-9
references.pmid: 12675486
references.citation: Neurosci Lett. 1997 Dec 5;238(3):127-30
references.pmid: 9464636
references.citation: Brain Res. 2008 Jan 10;1188:35-43
references.pmid: 18053973
references.citation: Vis Neurosci. 1991 Mar;6(3):257-69
references.pmid: 2054327
references.citation: Ann N Y Acad Sci. 2000;921:366-9
references.pmid: 11193854
references.citation: J Biol Chem. 2006 Mar 31;281(13):8788-95
references.pmid: 16446354
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10659-64
references.pmid: 12130665
references.citation: Neurotox Res. 2007 Sep;12(2):95-104
references.pmid: 17967733
references.citation: Doc Ophthalmol. 2009 Feb;118(1):55-61
references.pmid: 18483822
references.citation: Histol Histopathol. 2003 Oct;18(4):1219-42
references.pmid: 12973690
references.citation: J Cereb Blood Flow Metab. 2002 Apr;22(4):431-43
references.pmid: 11919514
references.citation: J Neurosci Res. 2003 Jul 15;73(2):206-14
references.pmid: 12836163
references.citation: Curr Eye Res. 2001 Apr;22(4):245-52
references.pmid: 11462162
references.citation: Biol Pharm Bull. 2007 Oct;30(10):1895-7
references.pmid: 17917258
references.citation: Stroke. 2003 Jul;34(7):1796-802
references.pmid: 12791941
references.citation: Can J Physiol Pharmacol. 2005 Jun;83(6):459-65
references.pmid: 16049545
references.citation: Brain Res Bull. 2004 Feb 15;62(6):461-6
references.pmid: 15036558
references.citation: Mol Pharmacol. 2001 Jun;59(6):1497-505
references.pmid: 11353811
references.citation: Int J Biochem Cell Biol. 2002 Aug;34(8):907-10
references.pmid: 12007627
references.citation: J Neurosci Res. 2004 Jun 1;76(5):697-704
references.pmid: 15139028
references.citation: J Pharmacol Exp Ther. 2001 Jan;296(1):216-23
references.pmid: 11123383
references.citation: Regul Pept. 2006 Nov 15;137(1-2):20-6
references.pmid: 16945433
references.citation: Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2750-6
references.pmid: 12766083
references.citation: Brain Res Dev Brain Res. 2005 May 12;156(2):193-201
references.pmid: 16099306
references.citation: Br J Ophthalmol. 1984 Jan;68(1):47-57
references.pmid: 6689935
references.citation: Am J Pathol. 2008 Jul;173(1):2-13
references.pmid: 18535182