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Photoreceptor Cell Death Mechanisms in Inherited Retinal Degeneration

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Abstract

Photoreceptor cell death is the major hallmark of a group of human inherited retinal degenerations commonly referred to as retinitis pigmentosa (RP). Although the causative genetic mutations are often known, the mechanisms leading to photoreceptor degeneration remain poorly defined. Previous research work has focused on apoptosis, but recent evidence suggests that photoreceptor cell death may result primarily from non-apoptotic mechanisms independently of AP1 or p53 transcription factor activity, Bcl proteins, caspases, or cytochrome c release. This review briefly describes some animal models used for studies of retinal degeneration, with particular focus on the rd1 mouse. After outlining the major features of different cell death mechanisms in general, we then compare them with results obtained in retinal degeneration models, where photoreceptor cell death appears to be governed by, among other things, changes in cyclic nucleotide metabolism, downregulation of the transcription factor CREB, and excessive activation of calpain and PARP. Based on recent experimental evidence, we propose a putative non-apoptotic molecular pathway for photoreceptor cell death in the rd1 retina. The notion that inherited photoreceptor cell death is driven by non-apoptotic mechanisms may provide new ideas for future treatment of RP.

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References

  1. Kolb H (2003) How the retina works. American Scientist 91:28–35

    Google Scholar 

  2. Hartong DT (2006) Retinitis pigmentosa. Lancet 368:1795–1809

    Article  PubMed  CAS  Google Scholar 

  3. Farrar GJ (2002) On the genetics of retinitis pigmentosa and on mutation-independent approaches to therapeutic intervention. EMBO J 21:857–864

    Article  PubMed  CAS  Google Scholar 

  4. Kennan A (2005) Light in retinitis pigmentosa. Trends Genet 21:103–110

    Article  PubMed  CAS  Google Scholar 

  5. Besch D (2003) Inherited multifocal RPE-diseases: mechanisms for local dysfunction in global retinoid cycle gene defects. Vision Res 43:3095–3108

    Article  PubMed  CAS  Google Scholar 

  6. Delyfer MN (2004) Inherited retinal degenerations: therapeutic prospects. Biol Cell 96:261–269

    Article  PubMed  CAS  Google Scholar 

  7. Pierce EA (2001) Pathways to photoreceptor cell death in inherited retinal degenerations. Bioessays 23:605–618

    Article  PubMed  CAS  Google Scholar 

  8. Bainbridge JW (2008) Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med 358:2231–2239

    Article  PubMed  CAS  Google Scholar 

  9. Chang GQ (1993) Apoptosis: final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice. Neuron 11:595–605

    Article  PubMed  CAS  Google Scholar 

  10. Marigo V (2007) Programmed cell death in retinal degeneration: targeting apoptosis in photoreceptors as potential therapy for retinal degeneration. Cell Cycle 6:652–655

    PubMed  CAS  Google Scholar 

  11. Doonan F (2005) Activation of multiple pathways during photoreceptor apoptosis in the rd mouse. Invest Ophthalmol Vis Sci 46:3530–3538

    Article  PubMed  Google Scholar 

  12. Portera-Cailliau C (1994) Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa. Proc Natl Acad Sci USA 91:974–978

    Article  PubMed  CAS  Google Scholar 

  13. Xu GZ (1996) Apoptosis in human retinal degenerations. Trans Am Ophthalmol Soc 94:411–30

    PubMed  CAS  Google Scholar 

  14. Rohrer B (2004) Multidestructive pathways triggered in photoreceptor cell death of the rd mouse as determined through gene expression profiling. J Biol Chem 279:41903–41910

    Article  PubMed  CAS  Google Scholar 

  15. Lohr HR (2006) Multiple, parallel cellular suicide mechanisms participate in photoreceptor cell death. Exp Eye Res 83:380–389

    Article  PubMed  CAS  Google Scholar 

  16. Paquet-Durand F (2007) Calpain activity in retinal degeneration. J Neurosci Res 85:693–702

    Article  PubMed  CAS  Google Scholar 

  17. Chang B (2002) Retinal degeneration mutants in the mouse. Vision Res 42:517–525

    Article  PubMed  CAS  Google Scholar 

  18. Dalke C (2005) Mouse mutants as models for congenital retinal disorders. Exp Eye Res 81:503–512

    Article  PubMed  CAS  Google Scholar 

  19. Keeler CE (1924) The inheritance of a retinal abnormality in white mice. Proc Natl Acad Sci USA 10:329–333

    Article  PubMed  CAS  Google Scholar 

  20. Bowes C (1990) Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMP-phosphodiesterase. Nature 347:677–680

    Article  PubMed  CAS  Google Scholar 

  21. Farber DB (1974) Cyclic guanosine monophosphate: elevation in degenerating photoreceptor cells of the C3H mouse retina. Science 186:449–451

    Article  PubMed  CAS  Google Scholar 

  22. Schoppner A (1984) Purification and properties of a stilbene synthase from induced cell suspension cultures of peanut. J Biol Chem 259:6806–6811

    PubMed  CAS  Google Scholar 

  23. Otani A (2004) Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative hematopoietic stem cells. J Clin Invest 114:765–774

    PubMed  CAS  Google Scholar 

  24. Punzo C (2007) Cellular responses to photoreceptor death in the rd1 mouse model of retinal degeneration. Invest Ophthalmol Vis Sci 48:849–857

    Article  PubMed  Google Scholar 

  25. Paquet-Durand F (2007) Excessive activation of poly(ADP-ribose) polymerase contributes to inherited photoreceptor degeneration in the retinal degeneration mouse 1. J Neurosci 27:10311–10319

    Article  PubMed  CAS  Google Scholar 

  26. Carter-Dawson LD (1978) Differential effect of the rd mutation on rods and cones in the mouse retina. Invest Ophthalmol Vis Sci 17:489–498

    PubMed  CAS  Google Scholar 

  27. LaVail MM (1997) Variability in rate of cone degeneration in the retinal degeneration (rd/rd) mouse. Exp Eye Res 65:45–50

    Article  PubMed  CAS  Google Scholar 

  28. Bayes M (1995) Homozygous tandem duplication within the gene encoding the beta-subunit of rod phosphodiesterase as a cause for autosomal recessive retinitis pigmentosa. Hum Mutat 5:228–234

    Article  PubMed  CAS  Google Scholar 

  29. Dryja TP (1999) Frequency of mutations in the gene encoding the alpha subunit of rod cGMP-phosphodiesterase in autosomal recessive retinitis pigmentosa. Invest Ophthalmol Vis Sci 40:1859–1865

    PubMed  CAS  Google Scholar 

  30. Chang B (2007) Two mouse retinal degenerations caused by missense mutations in the beta-subunit of rod cGMP phosphodiesterase gene. Vision Res 47:624–633

    Article  PubMed  CAS  Google Scholar 

  31. Gargini C (2007) Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: a morphological and ERG study. J Comp Neurol 500:222–238

    Article  PubMed  Google Scholar 

  32. Corrochano S (2008) Attenuation of vision loss and delay in apoptosis of photoreceptors induced by proinsulin in a mouse model of retinitis pigmentosa. Invest Ophthalmol Vis Sci 49:4188–4194

    Article  PubMed  Google Scholar 

  33. Lei B (2006) Study of rod- and cone-driven oscillatory potentials in mice. Invest Ophthalmol Vis Sci 47:2732–2738

    Article  PubMed  Google Scholar 

  34. Travis GH (1991) The retinal degeneration slow (rds) gene product is a photoreceptor disc membrane-associated glycoprotein. Neuron 6:61–70

    Article  PubMed  CAS  Google Scholar 

  35. Connell G (1991) Photoreceptor peripherin is the normal product of the gene responsible for retinal degeneration in the rds mouse. Proc Natl Acad Sci USA 88:723–726

    Article  PubMed  CAS  Google Scholar 

  36. Goldberg AF (2006) Role of peripherin/rds in vertebrate photoreceptor architecture and inherited retinal degenerations. Int Rev Cytol 253:131–175

    Article  PubMed  CAS  Google Scholar 

  37. Sanyal S (1980) Development and degeneration of retina in rds mutant mice: light microscopy. J Comp Neurol 194:193–207

    Article  PubMed  CAS  Google Scholar 

  38. Dryja TP (1997) Dominant and digenic mutations in the peripherin/RDS and ROM1 genes in retinitis pigmentosa. Invest Ophthalmol Vis Sci 38:1972–1982

    PubMed  CAS  Google Scholar 

  39. Pentia DC (2006) The glutamic acid-rich protein-2 (GARP2) is a high affinity rod photoreceptor phosphodiesterase (PDE6)-binding protein that modulates its catalytic properties. J Biol Chem 281:5500–5505

    Article  PubMed  CAS  Google Scholar 

  40. Wilson JH (2003) The nature of dominant mutations of rhodopsin and implications for gene therapy. Mol Neurobiol 28:149–158

    Article  PubMed  CAS  Google Scholar 

  41. Rivolta C (2002) Retinitis pigmentosa and allied diseases: numerous diseases, genes, and inheritance patterns. Hum Mol Genet 11:1219–1227

    Article  PubMed  CAS  Google Scholar 

  42. Lewin AS (1998) Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa. Nat Med 4:967–971

    Article  PubMed  CAS  Google Scholar 

  43. Lem J (1999) Morphological, physiological, and biochemical changes in rhodopsin knockout mice. Proc Natl Acad Sci USA 96:736–741

    Article  PubMed  CAS  Google Scholar 

  44. Mendes HF (2005) Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy. Trends Mol Med 11:177–185

    Article  PubMed  CAS  Google Scholar 

  45. Tam BM (2007) Dark rearing rescues P23H rhodopsin-induced retinal degeneration in a transgenic Xenopus laevis model of retinitis pigmentosa: a chromophore-dependent mechanism characterized by production of N-terminally truncated mutant rhodopsin. J Neurosci 27:9043–9053

    Article  PubMed  CAS  Google Scholar 

  46. Trumpler J (2008) Rod and cone contributions to horizontal cell light responses in the mouse retina. J Neurosci 28:6818–6825

    Article  PubMed  CAS  Google Scholar 

  47. Robinson PR (1994) Opsins with mutations at the site of chromophore attachment constitutively activate transducin but are not phosphorylated by rhodopsin kinase. Proc Natl Acad Sci USA 91:5411–5415

    Article  PubMed  CAS  Google Scholar 

  48. Andres A (2003) Altered functionality in rhodopsin point mutants associated with retinitis pigmentosa. Biochem Biophys Res Commun 303:294–301

    Article  PubMed  CAS  Google Scholar 

  49. Reme CE (1998) Apoptotic cell death in retinal degenerations. Prog Retin Eye Res 17:443–464

    Article  PubMed  CAS  Google Scholar 

  50. Hao W (2002) Evidence for two apoptotic pathways in light-induced retinal degeneration. Nat Genet 32:254–260

    Article  PubMed  CAS  Google Scholar 

  51. Wenzel A (2005) Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog Retin Eye Res 24:275–306

    Article  PubMed  CAS  Google Scholar 

  52. Donovan M (2001) Light-induced photoreceptor apoptosis in vivo requires neuronal nitric-oxide synthase and guanylate cyclase activity and is caspase-3-independent. J Biol Chem 276:23000–23008

    Article  PubMed  CAS  Google Scholar 

  53. Leist M (2001) Four deaths and a funeral: from caspases to alternative mechanisms. Nat Rev Mol Cell Biol 2:589–598

    Article  PubMed  CAS  Google Scholar 

  54. Kerr JF (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    PubMed  CAS  Google Scholar 

  55. Lockshin RA (2001) Programmed cell death and apoptosis: origins of the theory. Nat Rev Mol Cell Biol 2:545–550

    Article  PubMed  CAS  Google Scholar 

  56. Zeiss CJ (2003) The apoptosis–necrosis continuum: insights from genetically altered mice. Vet Pathol 40:481–495

    Article  PubMed  CAS  Google Scholar 

  57. Nicotera P (2002) Apoptosis and age-related disorders: role of caspase-dependent and caspase-independent pathways. Toxicol Lett 127:189–195

    Article  PubMed  CAS  Google Scholar 

  58. Eferl R (2003) AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer 3:859–868

    Article  PubMed  CAS  Google Scholar 

  59. Smeyne RJ (1993) Continuous c-fos expression precedes programmed cell death in vivo. Nature 363:166–169

    Article  PubMed  CAS  Google Scholar 

  60. Lowe SW (1993) p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74:957–967

    Article  PubMed  CAS  Google Scholar 

  61. Kerr JF (1994) Apoptosis. Its significance in cancer and cancer therapy. Cancer 73:2013–2026

    Article  PubMed  CAS  Google Scholar 

  62. Blomgren K (2007) Pathological apoptosis in the developing brain. Apoptosis 12:993–1010

    Article  PubMed  Google Scholar 

  63. Culmsee C (2005) Apoptosis-inducing factor triggered by poly(ADP-ribose) polymerase and Bid mediates neuronal cell death after oxygen-glucose deprivation and focal cerebral ischemia. J Neurosci 25:10262–10272

    Article  PubMed  CAS  Google Scholar 

  64. Edinger AL (2004) Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol 16:663–669

    Article  PubMed  CAS  Google Scholar 

  65. Bernardi P (1999) Mitochondria and cell death. Mechanistic aspects and methodological issues. Eur J Biochem 264:687–701

    Article  PubMed  CAS  Google Scholar 

  66. Gavrieli Y (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119:493–501

    Article  PubMed  CAS  Google Scholar 

  67. Grasl-Kraupp B (1995) In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: a cautionary note. Hepatology 21:1465–1468

    Article  PubMed  CAS  Google Scholar 

  68. Colicos MA (1996) Apoptotic morphology of dentate gyrus granule cells following experimental cortical impact injury in rats: possible role in spatial memory deficits. Brain Res 739:120–131

    Article  PubMed  CAS  Google Scholar 

  69. Choi DW (1996) Ischemia-induced neuronal apoptosis. Curr Opin Neurobiol 6:667–672

    Article  PubMed  CAS  Google Scholar 

  70. Zong WX (2006) Necrotic death as a cell fate. Genes Dev 20:1–15

    Article  PubMed  CAS  Google Scholar 

  71. Sloviter RS (2002) Apoptosis: a guide for the perplexed. Trends Pharmacol Sci 23:19–24

    Article  PubMed  CAS  Google Scholar 

  72. Yamashima T (2004) Ca2-dependent proteases in ischemic neuronal death: a conserved ‘calpain–cathepsin cascade’ from nematodes to primates. Cell Calcium 36:285–293

    Article  PubMed  CAS  Google Scholar 

  73. Roy M (1999) Neuronal apoptosis in acute necrotic insults: why is this subject such a mess. Trends Neurosci 22:419–422

    Article  PubMed  CAS  Google Scholar 

  74. Young RW (1984) Cell death during differentiation of the retina in the mouse. J Comp Neurol 229:362–373

    Article  PubMed  CAS  Google Scholar 

  75. Mervin K (2002) Developmental death of photoreceptors in the C57BL/6J mouse: association with retinal function and self-protection. Exp Eye Res 75:703–713

    Article  PubMed  CAS  Google Scholar 

  76. Valenciano AI (2008) Early neural cell death: numbers and cues from the developing neuroretina. Int J Dev Biol 52:2446–2446

    Google Scholar 

  77. Doonan F (2003) Caspase-independent photoreceptor apoptosis in mouse models of retinal degeneration. J Neurosci 23:5723–5731

    PubMed  CAS  Google Scholar 

  78. Zeiss CJ (2004) Caspase-3 in postnatal retinal development and degeneration. Invest Ophthalmol Vis Sci 45:964–970

    Article  PubMed  Google Scholar 

  79. Yoshizawa K (2002) Caspase-3 inhibitor transiently delays inherited retinal degeneration in C3H mice carrying the rd gene. Graefes Arch Clin Exp Ophthalmol 240:214–219

    Article  PubMed  CAS  Google Scholar 

  80. Liu X (2004) The role of calpain in oncotic cell death. Annu Rev Pharmacol Toxicol 44:349–370

    Article  PubMed  CAS  Google Scholar 

  81. Chrysostomou V (2008) The status of cones in the rhodopsin mutant P23H-3 retina: light-regulated damage and repair in parallel with rods. Invest Ophthalmol Vis Sci 49:1116–1125

    Article  PubMed  Google Scholar 

  82. Sahel JA (2001) Rod–cone interdependence: implications for therapy of photoreceptor cell diseases. Prog Brain Res 131:649–661

    Article  PubMed  CAS  Google Scholar 

  83. Huang PC (1993) Cellular interactions implicated in the mechanism of photoreceptor degeneration in transgenic mice expressing a mutant rhodopsin gene. Proc Natl Acad Sci USA 90:8484–8488

    Article  PubMed  CAS  Google Scholar 

  84. Mohand-Said S (1998) Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse. Proc Natl Acad Sci USA 95:8357–8362

    Article  PubMed  CAS  Google Scholar 

  85. Chalmel F (2007) Rod-derived Cone Viability Factor-2 is a novel bifunctional-thioredoxin-like protein with therapeutic potential. BMC Mol Biol 8:74

    Article  PubMed  CAS  Google Scholar 

  86. Cusato K (2003) Gap junctions mediate bystander cell death in developing retina. J Neurosci 23:6413–6422

    PubMed  CAS  Google Scholar 

  87. Ripps H (2002) Cell death in retinitis pigmentosa: gap junctions and the ‘bystander’ effect. Exp Eye Res 74:327–336

    Article  PubMed  CAS  Google Scholar 

  88. Shen J (2005) Oxidative damage is a potential cause of cone cell death in retinitis pigmentosa. J Cell Physiol 203:457–464

    Article  PubMed  CAS  Google Scholar 

  89. Yu DY (2005) Retinal degeneration and local oxygen metabolism. Exp Eye Res 80:745–751

    Article  PubMed  CAS  Google Scholar 

  90. Wellard J (2005) Photoreceptors in the rat retina are specifically vulnerable to both hypoxia and hyperoxia. Vis Neurosci 22:501–507

    Article  PubMed  Google Scholar 

  91. Zeiss CJ (2004) Proliferation of microglia, but not photoreceptors, in the outer nuclear layer of the rd-1 mouse. Invest Ophthalmol Vis Sci 45:971–976

    Article  PubMed  Google Scholar 

  92. Langmann T (2007) Microglia activation in retinal degeneration. J Leukoc Biol 81:1345–1351

    Article  PubMed  CAS  Google Scholar 

  93. Sancho-Pelluz J (2008) Sialoadhesin expression in intact degenerating retinas and following transplantation. Invest Ophthalmol Vis Sci (in press). doi:10.1167/iovs.08-2117

  94. Gehrs KM (2006) Age-related macular degeneration—emerging pathogenetic and therapeutic concepts. Ann Med 38:450–471

    Article  PubMed  Google Scholar 

  95. Joussen AM (2004) A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J 18:1450–1452

    PubMed  CAS  Google Scholar 

  96. Nakazawa T (2006) Tumor necrosis factor-alpha mediates oligodendrocyte death and delayed retinal ganglion cell loss in a mouse model of glaucoma. J Neurosci 26:12633–12641

    Article  PubMed  CAS  Google Scholar 

  97. Tezel G (2007) Mechanisms of immune system activation in glaucoma: oxidative stress-stimulated antigen presentation by the retina and optic nerve head glia. Invest Ophthalmol Vis Sci 48:705–714

    Article  PubMed  Google Scholar 

  98. Zeng HY (2005) Identification of sequential events and factors associated with microglial activation, migration, and cytotoxicity in retinal degeneration in rd mice. Invest Ophthalmol Vis Sci 46:2992–2999

    Article  PubMed  Google Scholar 

  99. Zhang C (2005) Activation of microglia and chemokines in light-induced retinal degeneration. Mol Vis 11:887–895

    PubMed  CAS  Google Scholar 

  100. Komeima K (2006) Antioxidants reduce cone cell death in a model of retinitis pigmentosa. Proc Natl Acad Sci USA 103:11300–11305

    Article  PubMed  CAS  Google Scholar 

  101. Strettoi E (2003) Remodeling of second-order neurons in the retina of rd/rd mutant mice. Vision Res 43:867–877

    Article  PubMed  Google Scholar 

  102. Frasson M (1999) Retinitis pigmentosa: rod photoreceptor rescue by a calcium-channel blocker in the rd mouse. Nat Med 5:1183–1187

    Article  PubMed  CAS  Google Scholar 

  103. Sharma AK (2004) Calcium-induced calpain mediates apoptosis via caspase-3 in a mouse photoreceptor cell line. J Biol Chem 279:35564–35572

    Article  PubMed  CAS  Google Scholar 

  104. Pawlyk BS (2002) Absence of photoreceptor rescue with D-cis-diltiazem in the rd mouse. Invest Ophthalmol Vis Sci 43:1912–1915

    PubMed  Google Scholar 

  105. Fiscus RR (2002) Involvement of cyclic GMP and protein kinase G in the regulation of apoptosis and survival in neural cells. Neurosignals 11:175–190

    Article  PubMed  CAS  Google Scholar 

  106. Silveira MS (2006) Neuroprotection by cAMP: another brick in the wall. Adv Exp Med Biol 557:164–176

    Article  PubMed  CAS  Google Scholar 

  107. McLaughlin ME (1993) Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa. Nat Genet 4:130–134

    Article  PubMed  CAS  Google Scholar 

  108. Yan W (1998) Selective degradation of nonsense beta-phosphodiesterase mRNA in the heterozygous rd mouse. Invest Ophthalmol Vis Sci 39:2529–2536

    PubMed  CAS  Google Scholar 

  109. Tucker CL (1999) Biochemical analysis of a dimerization domain mutation in RetGC-1 associated with dominant cone–rod dystrophy. Proc Natl Acad Sci USA 96:9039–9044

    Article  PubMed  CAS  Google Scholar 

  110. Payne AM (1998) A mutation in guanylate cyclase activator 1A (GUCA1A) in an autosomal dominant cone dystrophy pedigree mapping to a new locus on chromosome 6p21.1. Hum Mol Genet 7:273–277

    Article  PubMed  CAS  Google Scholar 

  111. Semple-Rowland SL (1999) rd and rc chickens carry the same GC1 null allele (GUCY1*). Exp Eye Res 69:579–581

    Article  PubMed  CAS  Google Scholar 

  112. Olshevskaya EV (2002) Factors that affect regulation of cGMP synthesis in vertebrate photoreceptors and their genetic link to human retinal degeneration. Mol Cell Biochem 230:139–147

    Article  PubMed  CAS  Google Scholar 

  113. Finkbeiner S (2000) CREB couples neurotrophin signals to survival messages 2. Neuron 25:11–14

    Article  PubMed  CAS  Google Scholar 

  114. Mantamadiotis T (2002) Disruption of CREB function in brain leads to neurodegeneration. Nat Genet 31:47–54

    Article  PubMed  CAS  Google Scholar 

  115. Lolley RN (1974) Alterations in cyclic AMP metabolism associated with photoreceptor cell degeneration in the C3H mouse. J Neurochem 22:701–707

    Article  PubMed  CAS  Google Scholar 

  116. Weiss ER (1995) Altered cAMP levels in retinas from transgenic mice expressing a rhodopsin mutant. Biochem Biophys Res Commun 216:755–761

    Article  PubMed  CAS  Google Scholar 

  117. Nir I (2001) Regulation of cAMP by light and dopamine receptors is dysfunctional in photoreceptors of dystrophic retinal degeneration slow (rds) mice. Exp Eye Res 73:265–272

    Article  PubMed  CAS  Google Scholar 

  118. Ding B (2005) A positive feedback loop of phosphodiesterase 3 (PDE3) and inducible cAMP early repressor (ICER) leads to cardiomyocyte apoptosis. Proc Natl Acad Sci USA 102:14771–14776

    Article  PubMed  CAS  Google Scholar 

  119. Mioduszewska B (2008) Inducible cAMP early repressor (ICER)-evoked delayed neuronal death in the organotypic hippocampal culture. J Neurosci Res 86:61–70

    Article  PubMed  CAS  Google Scholar 

  120. Chang YC (2006) Perinatal brain injury and regulation of transcription. Curr Opin Neurol 19:141–147

    Article  PubMed  CAS  Google Scholar 

  121. Hackam AS (2004) Identification of gene expression changes associated with the progression of retinal degeneration in the rd1 mouse. Invest Ophthalmol Vis Sci 45:2929–2942

    Article  PubMed  Google Scholar 

  122. Azadi S (2006) Up-regulation and increased phosphorylation of protein kinase C (PKC) delta, mu and theta in the degenerating rd1 mouse retina. Mol Cell Neurosci 31:759–773

    Article  PubMed  CAS  Google Scholar 

  123. Sheikh MS (2000) Role of p53 family members in apoptosis. J Cell Physiol 182:171–181

    Article  PubMed  CAS  Google Scholar 

  124. Ali RR (1998) Absence of p53 delays apoptotic photoreceptor cell death in the rds mouse. Curr Eye Res 17:917–923

    Article  PubMed  CAS  Google Scholar 

  125. Wu J (2001) Rod and cone degeneration in the rd mouse is p53 independent. Mol Vis 7:101–106

    PubMed  CAS  Google Scholar 

  126. Wenzel A (2000) c-fos controls the “private pathway” of light-induced apoptosis of retinal photoreceptors. J Neurosci 20:81–88

    PubMed  CAS  Google Scholar 

  127. Hafezi F (1998) Retinal degeneration in the rd mouse in the absence of c-fos. Invest Ophthalmol Vis Sci 39:2239–2244

    PubMed  CAS  Google Scholar 

  128. Takeda H (2007) Calcium/calmodulin-dependent protein kinase II regulates the phosphorylation of CREB in NMDA-induced retinal neurotoxicity. Brain Res 1184:306–315

    Article  PubMed  CAS  Google Scholar 

  129. Lonze BE (2002) Function and regulation of CREB family transcription factors in the nervous system. Neuron 35:605–623

    Article  PubMed  CAS  Google Scholar 

  130. Cong M (1998) cAMP responsiveness of the bovine calpastatin gene promoter. Biochim Biophys Acta 1443:186–192

    PubMed  CAS  Google Scholar 

  131. Zhang X (2005) Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci USA 102:4459–4464

    Article  PubMed  CAS  Google Scholar 

  132. Joseph RM (1996) Overexpression of Bcl-2 or Bcl-XL transgenes and photoreceptor degeneration. Invest Ophthalmol Vis Sci 37:2434–2446

    PubMed  CAS  Google Scholar 

  133. Rouaux C (2004) Targeting CREB-binding protein (CBP) loss of function as a therapeutic strategy in neurological disorders. Biochem Pharmacol 68:1157–1164

    Article  PubMed  CAS  Google Scholar 

  134. Rouaux C (2003) Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration. EMBO J 22:6537–6549

    Article  PubMed  CAS  Google Scholar 

  135. Rudolph D (1998) Impaired fetal T cell development and perinatal lethality in mice lacking the cAMP response element binding protein. Proc Natl Acad Sci USA 95:4481–4486

    Article  PubMed  CAS  Google Scholar 

  136. Paquet-Durand F (2006) Calpain is activated in degenerating photoreceptors in the rd1 mouse. J Neurochem 96:802–814

    Article  PubMed  CAS  Google Scholar 

  137. Johnson LE (2005) Differential Akt activation in the photoreceptors of normal and rd1 mice. Cell Tissue Res 320:213–222

    Article  PubMed  CAS  Google Scholar 

  138. Hauck SM (2006) Differential modification of phosducin protein in degenerating rd1 retina is associated with constitutively active Ca2+/calmodulin kinase II in rod outer segments. Mol Cell Proteomics 5:324–336

    PubMed  CAS  Google Scholar 

  139. Azadi S (2007) CNTF + BDNF treatment and neuroprotective pathways in the rd1 mouse retina. Brain Res 1129:116–129

    Article  PubMed  CAS  Google Scholar 

  140. Molina CA (1993) Inducibility and negative autoregulation of CREM: an alternative promoter directs the expression of ICER, an early response repressor. Cell 75:875–886

    Article  PubMed  CAS  Google Scholar 

  141. Allagnat F (2008) ICER-1gamma overexpression drives palmitate-mediated connexin36 down-regulation in insulin-secreting cells. J Biol Chem 283:5226–5234

    Article  PubMed  CAS  Google Scholar 

  142. Jaworski J (2003) Inducible cAMP early repressor, an endogenous antagonist of cAMP responsive element-binding protein, evokes neuronal apoptosis in vitro. J Neurosci 23:4519–4526

    PubMed  CAS  Google Scholar 

  143. Kristian T (1998) Calcium in ischemic cell death. Stroke 29:705–718

    PubMed  CAS  Google Scholar 

  144. Nicholls DG (2000) Mitochondrial membrane potential and neuronal glutamate excitotoxicity: mortality and millivolts. Trends Neurosci 23:166–174

    Article  PubMed  CAS  Google Scholar 

  145. Fox DA (1999) Calcium overload triggers rod photoreceptor apoptotic cell death in chemical-induced and inherited retinal degenerations. Ann N Y Acad Sci 893:282–285

    Article  PubMed  CAS  Google Scholar 

  146. Takano Y (2004) Study of drug effects of calcium channel blockers on retinal degeneration of rd mouse. Biochem Biophys Res Commun 313:1015–1022

    Article  PubMed  CAS  Google Scholar 

  147. Takeuchi K (2008) Systemic administration of nilvadipine delays photoreceptor degeneration of heterozygous retinal degeneration slow (rds) mouse. Exp Eye Res 86:60–69

    Article  PubMed  CAS  Google Scholar 

  148. Orrenius S (2003) Regulation of cell death: the calcium–apoptosis link. Nat Rev Mol Cell Biol 4:552–565

    Article  PubMed  CAS  Google Scholar 

  149. Guerini D (2005) Exporting calcium from cells. Cell Calcium 38:281–289

    Article  PubMed  CAS  Google Scholar 

  150. Leist M (1997) Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med 185:1481–1486

    Article  PubMed  CAS  Google Scholar 

  151. Pearce-Kelling SE (2001) Calcium channel blocker D-cis-diltiazem does not slow retinal degeneration in the PDE6B mutant rcd1 canine model of retinitis pigmentosa. Mol Vis 7:42–47

    PubMed  CAS  Google Scholar 

  152. Read DS (2002) Absence of voltage-dependent calcium channels delays photoreceptor degeneration in rd mice. Exp Eye Res 75:415–420

    Article  PubMed  CAS  Google Scholar 

  153. Uckermann O (2004) Selective staining by vital dyes of Muller glial cells in retinal wholemounts. Glia 45:59–66

    Article  PubMed  Google Scholar 

  154. Panfoli I (2007) Localization of the cyclic ADP-ribose-dependent calcium signaling pathway in bovine rod outer segments. Invest Ophthalmol Vis Sci 48:978–984

    Article  PubMed  Google Scholar 

  155. Szegezdi E (2006) Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 7:880–885

    Article  PubMed  CAS  Google Scholar 

  156. Schroder M (2005) The mammalian unfolded protein response. Annu Rev Biochem 74:739–789

    Article  PubMed  CAS  Google Scholar 

  157. Lindholm D (2006) ER stress and neurodegenerative diseases. Cell Death Differ 13:385–392

    Article  PubMed  CAS  Google Scholar 

  158. Lin JH (2007) IRE1 signaling affects cell fate during the unfolded protein response. Science 318:944–949

    Article  PubMed  CAS  Google Scholar 

  159. Sanges D (2006) Cross-talk between two apoptotic pathways activated by endoplasmic reticulum stress: differential contribution of caspase-12 and AIF. Apoptosis 11:1629–1641

    Article  PubMed  CAS  Google Scholar 

  160. Yang LP (2007) Activation of endoplasmic reticulum stress in degenerating photoreceptors of the rd1 mouse. Invest Ophthalmol Vis Sci 48:5191–5198

    Article  PubMed  Google Scholar 

  161. Shinohara T (2008) Silencing gene therapy for mutant membrane, secretory, and lipid proteins in retinitis pigmentosa (RP). Med Hypotheses 70:378–380

    Article  PubMed  CAS  Google Scholar 

  162. Suzuki K (2004) Structure, activation, and biology of calpain. Diabetes 53 Suppl 1:S12–18

    Article  Google Scholar 

  163. Goll DE (2003) The calpain system. Physiol Rev 83:731–801

    PubMed  CAS  Google Scholar 

  164. Hood JL (2004) Differential compartmentalization of the calpain/calpastatin network with the endoplasmic reticulum and Golgi apparatus. J Biol Chem 279:43126–43135

    Article  PubMed  CAS  Google Scholar 

  165. Li H (2004) Effects of autolysis on properties of mu- and m-calpain. Biochim Biophys Acta 1691:91–103

    Article  PubMed  CAS  Google Scholar 

  166. Wingrave JM (2004) Higher calpastatin levels correlate with resistance to calpain-mediated proteolysis and neuronal apoptosis in juvenile rats after spinal cord injury. J Neurotrauma 21:1240–1254

    Article  PubMed  Google Scholar 

  167. Higuchi M (2005) Distinct mechanistic roles of calpain and caspase activation in neurodegeneration as revealed in mice overexpressing their specific inhibitors. J Biol Chem 280:15229–15237

    Article  PubMed  CAS  Google Scholar 

  168. Cao G (2007) Critical role of calpain I in mitochondrial release of apoptosis-inducing factor in ischemic neuronal injury. J Neurosci 27:9278–9293

    Article  PubMed  CAS  Google Scholar 

  169. Araujo CL (2004) Calpain inhibitor 2 prevents axonal degeneration of opossum optic nerve fibers. J Neurosci Res 77:410–419

    Article  CAS  Google Scholar 

  170. Chiu K (2005) Calpain and N-methyl-d-aspartate (NMDA)-induced excitotoxicity in rat retinas. Brain Res 1046:207–215

    Article  PubMed  CAS  Google Scholar 

  171. Das A (2006) Calpeptin provides functional neuroprotection to rat retinal ganglion cells following Ca2+ influx. Brain Res 1084:146–157

    Article  PubMed  CAS  Google Scholar 

  172. Sanges D (2006) Apoptosis in retinal degeneration involves cross-talk between apoptosis-inducing factor (AIF) and caspase-12 and is blocked by calpain inhibitors. Proc Natl Acad Sci USA 103:17366–17371

    Article  PubMed  CAS  Google Scholar 

  173. Croall DE (2007) The calpains: modular designs and functional diversity. Genome Biol 8:218

    Article  PubMed  CAS  Google Scholar 

  174. Azarian SM (1995) Selective proteolysis of arrestin by calpain. Molecular characteristics and its effect on rhodopsin dephosphorylation. J Biol Chem 270:24375–24384

    Article  PubMed  CAS  Google Scholar 

  175. Buki KG (1997) Isolation and identification of a proteinase from calf thymus that cleaves poly(ADP-ribose) polymerase and histone H1. Biochim Biophys Acta 1338:100–106

    PubMed  CAS  Google Scholar 

  176. Hill JW (2008) OGG1 is degraded by calpain following oxidative stress and cisplatin exposure. DNA Repair (Amst) 7:648–654

    CAS  Google Scholar 

  177. Ahuja-Jensen P (2007) Low glutathione peroxidase in rd1 mouse retina increases oxidative stress and proteases. Neuroreport 18:797–801

    Article  PubMed  CAS  Google Scholar 

  178. Ahuja S (2008) rd1 Mouse retina shows an imbalance in the activity of cysteine protease cathepsins and their endogenous inhibitor cystatin C. Invest Ophthalmol Vis Sci 49:1089–1096

    Article  PubMed  Google Scholar 

  179. Sies H (1997) Oxidative stress: oxidants and antioxidants. Exp Physiol 82:291–295

    PubMed  CAS  Google Scholar 

  180. Cadet J (2000) Oxidative base damage to DNA: specificity of base excision repair enzymes. Mutat Res 462:121–128

    Article  PubMed  CAS  Google Scholar 

  181. Puertas FJ (1993) Glutathione system of human retina: enzymatic conjugation of lipid peroxidation products. Free Radic Biol Med 14:549–551

    Article  PubMed  CAS  Google Scholar 

  182. Ahuja P (2005) Decreased glutathione transferase levels in rd1/rd1 mouse retina: replenishment protects photoreceptors in retinal explants. Neuroscience 131:935–943

    PubMed  CAS  Google Scholar 

  183. Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now. J Neurochem 97:1634–1658

    Article  PubMed  CAS  Google Scholar 

  184. Constantinescu A (1993) Vitamin E recycling in human erythrocyte membranes. J Biol Chem 268:10906–10913

    PubMed  CAS  Google Scholar 

  185. Marcum JL (2005) Oxidation of thiol-proteases in the hippocampus of Alzheimer’s disease. Biochem Biophys Res Commun 334:342–348

    Article  PubMed  CAS  Google Scholar 

  186. Pignol B (2006) Calpain inhibitors and antioxidants act synergistically to prevent cell necrosis: effects of the novel dual inhibitors (cysteine protease inhibitor and antioxidant) BN 82204 and its pro-drug BN 82270. J Neurochem 98:1217–1228

    Article  PubMed  CAS  Google Scholar 

  187. Sanz MM (2007) Significant photoreceptor rescue by treatment with a combination of antioxidants in an animal model for retinal degeneration. Neuroscience 145:1120–1129

    Article  PubMed  CAS  Google Scholar 

  188. Chucair AJ (2007) Lutein and zeaxanthin protect photoreceptors from apoptosis induced by oxidative stress: relation with docosahexaenoic acid. Invest Ophthalmol Vis Sci 48:5168–5177

    Article  PubMed  Google Scholar 

  189. Arrington DD (2006) Calpain 10: a mitochondrial calpain and its role in calcium-induced mitochondrial dysfunction. Am J Physiol Cell Physiol 291:C1159–C1171

    Article  PubMed  CAS  Google Scholar 

  190. Artus C (2006) CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells. Oncogene 25:5741–5751

    Article  PubMed  CAS  Google Scholar 

  191. Vahsen N (2004) AIF deficiency compromises oxidative phosphorylation. EMBO J 23:4679–4689

    Article  PubMed  CAS  Google Scholar 

  192. Ray SK (2000) Oxidative stress and Ca2+ influx upregulate calpain and induce apoptosis in PC12 cells. Brain Res 852:326–334

    Article  PubMed  CAS  Google Scholar 

  193. Sanvicens N (2004) Oxidative stress-induced apoptosis in retinal photoreceptor cells is mediated by calpains and caspases and blocked by the oxygen radical scavenger CR-6. J Biol Chem 279:39268–39278

    Article  PubMed  CAS  Google Scholar 

  194. Miura S (2006) Intraventricular ascorbic acid administration decreases hypoxic–ischemic brain injury in newborn rats. Brain Res 1095:159–166

    Article  PubMed  CAS  Google Scholar 

  195. Oka S (2008) Two distinct pathways of cell death triggered by oxidative damage to nuclear and mitochondrial DNAs. EMBO J 27:421–432

    Article  PubMed  CAS  Google Scholar 

  196. McCollum AT (2004) Oxidative stress inhibits ionomycin-mediated cell death in cortical neurons. J Neurosci Res 76:104–109

    Article  PubMed  CAS  Google Scholar 

  197. Kasai H (1984) Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents. Nucleic Acids Res 12:2137–2145

    Article  PubMed  CAS  Google Scholar 

  198. Maki H (2002) Origins of spontaneous mutations: specificity and directionality of base-substitution, frameshift, and sequence-substitution mutageneses. Annu Rev Genet 36:279–303

    Article  PubMed  CAS  Google Scholar 

  199. Shakibaei M (2007) Resveratrol inhibits IL-1 beta-induced stimulation of caspase-3 and cleavage of PARP in human articular chondrocytes in vitro. Ann N Y Acad Sci 1095:554–563

    Article  PubMed  CAS  Google Scholar 

  200. Schreiber V (2006) Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol 7:517–528

    Article  PubMed  CAS  Google Scholar 

  201. Sims JL (1983) Poly(ADP-ribose) polymerase inhibitors preserve nicotinamide adenine dinucleotide and adenosine 5″-triphosphate pools in DNA-damaged cells: mechanism of stimulation of unscheduled DNA synthesis. Biochemistry 22:5188–5194

    Article  PubMed  CAS  Google Scholar 

  202. Du L (2003) Intra-mitochondrial poly(ADP-ribosylation) contributes to NAD depletion and cell death induced by oxidative stress. J Biol Chem 278:18426–18433

    Article  PubMed  CAS  Google Scholar 

  203. Boujrad H (2007) AIF-mediated programmed necrosis: a highly regulated way to die. Cell Cycle 6:2612–2619

    PubMed  CAS  Google Scholar 

  204. Scott GS (2004) Poly(ADP-ribose) polymerase activity contributes to peroxynitrite-induced spinal cord neuronal cell death in vitro. J Neurotrauma 21:1255–1263

    PubMed  Google Scholar 

  205. Koh DW (2005) Mediation of cell death by poly(ADP-ribose) polymerase-1. Pharmacol Res 52:5–14

    Article  PubMed  CAS  Google Scholar 

  206. Jagtap P (2005) Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat Rev Drug Discov 4:421–440

    Article  PubMed  CAS  Google Scholar 

  207. Yu SH (2006) Contents comparison of resveratrol and polydatin in the wild Polygonum cuspidatum plant and its tissue cultures. Zhongguo Zhong Yao Za Zhi 31:637–641

    PubMed  CAS  Google Scholar 

  208. Andrabi SA (2006) Poly(ADP-ribose) (PAR) polymer is a death signal. Proc Natl Acad Sci USA 103:18308–18313

    Article  PubMed  CAS  Google Scholar 

  209. D'Amours D (2001) Gain-of-function of poly(ADP-ribose) polymerase-1 upon cleavage by apoptotic proteases: implications for apoptosis. J Cell Sci 114:3771–3778

    PubMed  Google Scholar 

  210. Nguewa PA (2005) Poly(ADP-ribose) polymerases: homology, structural domains and functions. Novel therapeutical applications. Prog Biophys Mol Biol 88:143–172

    Article  PubMed  CAS  Google Scholar 

  211. Lazebnik YA (1994) Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature 371:346–347

    Article  PubMed  CAS  Google Scholar 

  212. McGinnis KM (1999) Procaspase-3 and poly(ADP)ribose polymerase (PARP) are calpain substrates. Biochem Biophys Res Commun 263:94–99

    Article  PubMed  CAS  Google Scholar 

  213. Wang S (2000) Progressive optic axon dystrophy and vascular changes in rd mice. Invest Ophthalmol Vis Sci 41:537–545

    PubMed  CAS  Google Scholar 

  214. Boland B (2003) beta-Amyloid (1–40)-induced apoptosis of cultured cortical neurones involves calpain-mediated cleavage of poly-ADP-ribose polymerase. Neurobiol Aging 24:179–186

    Article  PubMed  CAS  Google Scholar 

  215. Mendoza-Alvarez H (2004) The 40 kDa carboxy-terminal domain of poly(ADP-ribose) polymerase-1 forms catalytically competent homo- and heterodimers in the absence of DNA. J Mol Biol 336:105–114

    Article  PubMed  CAS  Google Scholar 

  216. Moubarak RS (2007) Sequential activation of poly(ADP-ribose) polymerase 1, calpains, and Bax is essential in apoptosis-inducing factor-mediated programmed necrosis. Mol Cell Biol 27:4844–4862

    Article  PubMed  CAS  Google Scholar 

  217. Lorenzo HK (2007) Therapeutic potential of AIF-mediated caspase-independent programmed cell death. Drug Resist Updat 10:235–255

    Article  PubMed  CAS  Google Scholar 

  218. Joza N (2001) Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature 410:549–554

    Article  PubMed  CAS  Google Scholar 

  219. Klein JA (2002) The harlequin mouse mutation downregulates apoptosis-inducing factor. Nature 419:367–374

    Article  PubMed  CAS  Google Scholar 

  220. Yu SW (2002) Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 297:259–263

    Article  PubMed  CAS  Google Scholar 

  221. Williams DS (1987) Photoreceptor degeneration in a pure-cone retina. Effects of cyclic nucleotides, and inhibitors of phosphodiesterase and protein synthesis. Invest Ophthalmol Vis Sci 28:1059–1069

    PubMed  CAS  Google Scholar 

  222. Tsang SH (1996) Retinal degeneration in mice lacking the gamma subunit of the rod cGMP phosphodiesterase. Science 272:1026–1029

    Article  PubMed  CAS  Google Scholar 

  223. Ramamurthy V (2004) Leber congenital amaurosis linked to AIPL1: a mouse model reveals destabilization of cGMP phosphodiesterase. Proc Natl Acad Sci USA 101:13897–13902

    Article  PubMed  CAS  Google Scholar 

  224. Karan S (2008) A model for transport of membrane-associated phototransduction polypeptides in rod and cone photoreceptor inner segments. Vision Res 48:442–452

    Article  PubMed  CAS  Google Scholar 

  225. Nishiguchi KM (2004) A novel mutation (I143NT) in guanylate cyclase-activating protein 1 (GCAP1) associated with autosomal dominant cone degeneration. Invest Ophthalmol Vis Sci 45:3863–3870

    Article  PubMed  Google Scholar 

  226. Komeima K (2008) Blockade of neuronal nitric oxide synthase reduces cone cell death in a model of retinitis pigmentosa. Free Radic Biol Med 45:905–912

    Article  PubMed  CAS  Google Scholar 

  227. Doonan F (2004) Apoptosis: a potential therapeutic target for retinal degenerations. Curr Neurovasc Res 1:41–53

    Article  PubMed  CAS  Google Scholar 

  228. Jimenez AJ (1996) The spatio-temporal pattern of photoreceptor degeneration in the aged rd/rd mouse retina. Cell Tissue Res 284:193–202

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We apologize to those colleagues working on retinal degeneration whose work was not cited in this review due to space constraints. Parts of the work presented here have been supported by grants from the Kerstan foundation, the German research council (DFG), the European Union (RETNET, MRTN-CT-2003-504003; EVI-GENORET, LSHG-CT-2005-512036; NEUROTRAIN, MEST-CT-2005-020235), Foundation Fighting Blindness (FFB), Petrus och Augusta Hedlunds Stiftelse, Dutch Retina Foundation, Kronprinsessan Margaretas Arbetsnämnd för synskadade (KMA), Synfrämjandets Forskningsfond, Torsten och Ragnar Söderbergs Stiftelser, Vetenskapsrådet medicin (VRM), the Crafoord Foundation, and Fundación Oftalmológica del Mediterráneo (FOM).

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Authors and Affiliations

  1. Institute for Ophthalmic Research, University of Tübingen, Centre for Ophthalmology, Röntgenweg 11, 72076, Tübingen, Germany

    Javier Sancho-Pelluz, Blanca Arango-Gonzalez, Stefan Kustermann, Theo van Veen, Eberhart Zrenner & François Paquet-Durand

  2. Department of Ophthalmology, Clinical Sciences, Lund, BMC B13, 22184, Lund, Sweden

    Theo van Veen & Per Ekström

  3. Fundación Oftalmológica del Mediterráneo (FOM), Bifurcación Pio Baroja-General Avilés, s/n 46015, Valencia, Spain

    Javier Sancho-Pelluz & Francisco Javier Romero

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  1. Javier Sancho-Pelluz
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Correspondence to François Paquet-Durand.

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Sancho-Pelluz, J., Arango-Gonzalez, B., Kustermann, S. et al. Photoreceptor Cell Death Mechanisms in Inherited Retinal Degeneration. Mol Neurobiol 38, 253–269 (2008). https://doi.org/10.1007/s12035-008-8045-9

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