Photoreceptor cell death and rescue in retinal detachment and degenerations |
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| Institution: | 1. Retina Service, Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA;2. Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan;3. Department of Ophthalmology, Tohoku University, Graduate School of Medicine, Sendai 980-8574, Japan;1. Mary D. Allen Laboratory for Vision Research, USC Eye Institute, Keck School of Medicine of the University of Southern California, USA;2. Department of Ophthalmology, Keck School of Medicine of the University of Southern California, USA;3. Department of Cell & Neurobiology, Keck School of Medicine of the University of Southern California, USA;4. Department of Anatomy, School of Medicine, Ewha Womans University, Seoul 158-710, South Korea;5. Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA;6. Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA;7. Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, USA;8. University of Southern California Viterbi School of Engineering, Los Angeles, CA, USA;9. Department of Neuroscience, Georgetown University, Washington D.C, USA;10. Department of Physics, Georgetown University, Washington D.C, USA;1. Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China;2. Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China;3. Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA;4. Departments of Pharmacology, Case Western Reserve University, Cleveland, OH, 44106, USA |
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| 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. |
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| Keywords: | Retina Macula Degenerations Necrosis Apoptosis Autophagy Neuroprotection Neuroregeneration |
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