title: Photoreceptor cell death mechanisms in inherited retinal degeneration.
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.
authors.affiliation: Institute for Ophthalmic Research, University of Tübingen, Centre for Ophthalmology, Röntgenweg 11, 72076, Tübingen, Germany.
authors.forename: Javier
authors.initials: J
authors.lastname: Sancho-Pelluz
authors.forename: Blanca
authors.initials: B
authors.lastname: Arango-Gonzalez
authors.forename: Stefan
authors.initials: S
authors.lastname: Kustermann
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Romero
authors.forename: Theo
authors.initials: T
authors.lastname: van Veen
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
authors.forename: Per
authors.initials: P
authors.lastname: Ekström
authors.forename: François
authors.initials: F
authors.lastname: Paquet-Durand
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D016923:Cell Death; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000473:pathology; D006801:Humans; D051379:Mice; D009712:Nucleotides, Cyclic / Q000378:metabolism; D018384:Oxidative Stress; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D012162:Retinal Degeneration / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009712:Nucleotides, Cyclic; D014157:Transcription Factors; D002154:Calpain; D002118:Calcium