title: Photoreceptor cell death and rescue in retinal detachment and degenerations.
abstract: Photoreceptor cell death is the ultimate cause of vision loss in various retinal disorders, including retinal detachment (RD). Photoreceptor cell death has been thought to occur mainly through apoptosis, which is the most characterized form of programmed cell death. The caspase family of cysteine proteases plays a central role for inducing apoptosis, and in experimental models of RD, dying photoreceptor cells exhibit caspase activation; however, there is a paradox that caspase inhibition alone does not provide a sufficient protection against photoreceptor cell loss, suggesting that other mechanisms of cell death are involved. Recent accumulating evidence demonstrates that non-apoptotic forms of cell death, such as autophagy and necrosis, are also regulated by specific molecular machinery, such as those mediated by autophagy-related proteins and receptor-interacting protein kinases, respectively. Here we summarize the current knowledge of cell death signaling and its roles in photoreceptor cell death after RD and other retinal degenerative diseases. A body of studies indicate that not only apoptotic but also autophagic and necrotic signaling are involved in photoreceptor cell death, and that combined targeting of these pathways may be an effective neuroprotective strategy for retinal diseases associated with photoreceptor cell loss.
authors.affiliation: Retina Service, Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA; Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murakami
authors.forename: Shoji
authors.initials: S
authors.lastname: Notomi
authors.forename: Toshio
authors.initials: T
authors.lastname: Hisatomi
authors.forename: Toru
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Joan W
authors.initials: JW
authors.lastname: Miller
authors.forename: Demetrios G
authors.initials: DG
authors.lastname: Vavvas
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D020169:Caspases / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000502:physiology; D006801:Humans; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D012162:Retinal Degeneration / Q000503:physiopathology*; D012163:Retinal Detachment / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D020690:GTPase-Activating Proteins; D020169:Caspases
keywords: Apoptosis; Autophagy; Degenerations; Macula; Necrosis; Neuroprotection; Neuroregeneration; Retina