{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T07:04:01Z","timestamp":1770275041349,"version":"3.49.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T00:00:00Z","timestamp":1492646400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T00:00:00Z","timestamp":1492646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Retinal ganglion cell (RGC) death is part of many retinal diseases. Here, we report that the ethanol extract of <jats:italic>Diospyros kaki<\/jats:italic> (EEDK) exhibits protective properties against retinal degeneration, both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Upon exposure to cytotoxic compounds, RGC-5 cells showed approximately 40% cell viability versus the control, while pre-treatment with EEDK markedly increased cell viability in a concentration-dependent manner. Further studies revealed that cell survival induced by EEDK was associated with decreased levels of apoptotic proteins, such as poly (ADP-ribose) polymerase, p53, and cleaved caspase-3. In addition to apoptotic pathways, we demonstrated that expression levels of antioxidant-associated proteins, such as superoxide dismutase-1, glutathione S-transferase, and glutathione peroxidase-1, were positively modulated by EEDK. In a partial optic nerve crush mouse model, EEDK had similar ameliorating effects on retinal degeneration resulting from mechanical damages. Therefore, our results suggest that EEDK may have therapeutic potential against retinal degenerative disorders, such as glaucoma.<\/jats:p>","DOI":"10.1038\/srep46449","type":"journal-article","created":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T09:19:42Z","timestamp":1492679982000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Persimmon Leaves (Diospyros kaki) Extract Protects Optic Nerve Crush-Induced Retinal Degeneration"],"prefix":"10.1038","volume":"7","author":[{"given":"Hong","family":"Ryul Ahn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung-A","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suk Woo","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joo Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae-Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Hoon","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,4,20]]},"reference":[{"key":"BFsrep46449_CR1","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/nrn1497","volume":"5","author":"H Wassle","year":"2004","unstructured":"Wassle, H. Parallel processing in the mammalian retina. Nat Rev Neurosci 5, 747\u2013757, doi: 10.1038\/nrn1497 (2004).","journal-title":"Nat Rev Neurosci"},{"key":"BFsrep46449_CR2","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S1350-9462(00)00027-6","volume":"20","author":"DY Yu","year":"2001","unstructured":"Yu, D. Y. & Cringle, S. J. Oxygen distribution and consumption within the retina in vascularised and avascular retinas and in animal models of retinal disease. Prog Retin Eye Res 20, 175\u2013208 (2001).","journal-title":"Prog Retin Eye Res"},{"key":"BFsrep46449_CR3","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S0039-6257(00)00140-5","volume":"45","author":"S Beatty","year":"2000","unstructured":"Beatty, S., Koh, H., Phil, M., Henson, D. & Boulton, M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 45, 115\u2013134 (2000).","journal-title":"Surv Ophthalmol"},{"key":"BFsrep46449_CR4","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1089\/ars.2015.6327","volume":"23","author":"PA Campochiaro","year":"2015","unstructured":"Campochiaro, P. A. et al. Is There Excess Oxidative Stress and Damage in Eyes of Patients with Retinitis Pigmentosa? Antioxid Redox Signal 23, 643\u2013648, doi: 10.1089\/ars.2015.6327 (2015).","journal-title":"Antioxid Redox Signal"},{"key":"BFsrep46449_CR5","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.preteyeres.2015.05.001","volume":"48","author":"RA Kowluru","year":"2015","unstructured":"Kowluru, R. A., Kowluru, A., Mishra, M. & Kumar, B. Oxidative stress and epigenetic modifications in the pathogenesis of diabetic retinopathy. Prog Retin Eye Res 48, 40\u201361, doi: 10.1016\/j.preteyeres.2015.05.001 (2015).","journal-title":"Prog Retin Eye Res"},{"key":"BFsrep46449_CR6","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/bs.pbr.2015.06.001","volume":"220","author":"MD Pinazo-Duran","year":"2015","unstructured":"Pinazo-Duran, M. D., Zanon-Moreno, V., Gallego-Pinazo, R. & Garcia-Medina, J. J. Oxidative stress and mitochondrial failure in the pathogenesis of glaucoma neurodegeneration. Prog Brain Res 220, 127\u2013153, doi: 10.1016\/bs.pbr.2015.06.001 (2015).","journal-title":"Prog Brain Res"},{"key":"BFsrep46449_CR7","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1167\/iovs.04-0832","volume":"46","author":"L Guo","year":"2005","unstructured":"Guo, L. et al. Retinal ganglion cell apoptosis in glaucoma is related to intraocular pressure and IOP-induced effects on extracellular matrix. Investigative ophthalmology & visual science 46, 175\u2013182, doi: 10.1167\/iovs.04-0832 (2005).","journal-title":"Investigative ophthalmology & visual science"},{"key":"BFsrep46449_CR8","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1167\/iovs.11-8525","volume":"53","author":"LM Ventura","year":"2012","unstructured":"Ventura, L. M., Feuer, W. J. & Porciatti, V. Progressive loss of retinal ganglion cell function is hindered with IOP-lowering treatment in early glaucoma. Investigative ophthalmology & visual science 53, 659\u2013663, doi: 10.1167\/iovs.11-8525 (2012).","journal-title":"Investigative ophthalmology & visual science"},{"key":"BFsrep46449_CR9","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1055\/s-0032-1327825","volume":"230","author":"A Cybulska-Heinrich","year":"2013","unstructured":"Cybulska-Heinrich, A., Mozaffarieh, M. & Flammer, J. [Value of non-IOP lowering therapy for glaucoma]. Klinische Monatsblatter fur Augenheilkunde 230, 114\u2013119, doi: 10.1055\/s-0032-1327825 (2013).","journal-title":"Klinische Monatsblatter fur Augenheilkunde"},{"key":"BFsrep46449_CR10","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1097\/00055735-200404000-00008","volume":"15","author":"MC Leske","year":"2004","unstructured":"Leske, M. C., Heijl, A., Hyman, L., Bengtsson, B. & Komaroff, E. Factors for progression and glaucoma treatment: the Early Manifest Glaucoma Trial. Current opinion in ophthalmology 15, 102\u2013106 (2004).","journal-title":"Current opinion in ophthalmology"},{"key":"BFsrep46449_CR11","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1172\/JCI11003","volume":"106","author":"JM Lee","year":"2000","unstructured":"Lee, J. M., Grabb, M. C., Zipfel, G. J. & Choi, D. W. Brain tissue responses to ischemia. The Journal of clinical investigation 106, 723\u2013731, doi: 10.1172\/JCI11003 (2000).","journal-title":"The Journal of clinical investigation"},{"key":"BFsrep46449_CR12","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.1523\/JNEUROSCI.12-05-01882.1992","volume":"12","author":"RD Randall","year":"1992","unstructured":"Randall, R. D. & Thayer, S. A. Glutamate-induced calcium transient triggers delayed calcium overload and neurotoxicity in rat hippocampal neurons. J Neurosci 12, 1882\u20131895 (1992).","journal-title":"J Neurosci"},{"key":"BFsrep46449_CR13","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.taap.2013.03.017","volume":"269","author":"KA Kim","year":"2013","unstructured":"Kim, K. A., Shim, S. H., Ahn, H. R. & Jung, S. H. Protective effects of the compounds isolated from the seed of Psoralea corylifolia on oxidative stress-induced retinal damage. Toxicol Appl Pharmacol 269, 109\u2013120, doi: 10.1016\/j.taap.2013.03.017 (2013).","journal-title":"Toxicol Appl Pharmacol"},{"key":"BFsrep46449_CR14","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/nrd3745","volume":"11","author":"K Zhang","year":"2012","unstructured":"Zhang, K., Zhang, L. & Weinreb, R. N. Ophthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucoma. Nat Rev Drug Discov 11, 541\u2013559, doi: 10.1038\/nrd3745 (2012).","journal-title":"Nat Rev Drug Discov"},{"key":"BFsrep46449_CR15","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/bs.pbr.2015.05.005","volume":"220","author":"H Levkovitch-Verbin","year":"2015","unstructured":"Levkovitch-Verbin, H. Retinal ganglion cell apoptotic pathway in glaucoma: Initiating and downstream mechanisms. Prog Brain Res 220, 37\u201357, doi: 10.1016\/bs.pbr.2015.05.005 (2015).","journal-title":"Prog Brain Res"},{"key":"BFsrep46449_CR16","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1097\/00061198-199610000-00010","volume":"5","author":"RW Nickells","year":"1996","unstructured":"Nickells, R. W. Retinal ganglion cell death in glaucoma: the how, the why, and the maybe. J Glaucoma 5, 345\u2013356 (1996).","journal-title":"J Glaucoma"},{"key":"BFsrep46449_CR17","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/bs.pbr.2015.04.012","volume":"220","author":"J Agostinone","year":"2015","unstructured":"Agostinone, J. & Di Polo, A. Retinal ganglion cell dendrite pathology and synapse loss: Implications for glaucoma. Prog Brain Res 220, 199\u2013216, doi: 10.1016\/bs.pbr.2015.04.012 (2015).","journal-title":"Prog Brain Res"},{"key":"BFsrep46449_CR18","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1271\/bbb.70.999","volume":"70","author":"SY Kim","year":"2006","unstructured":"Kim, S. Y. et al. Effect of heat treatment on the antioxidative and antigenotoxic activity of extracts from persimmon (Diospyros kaki L.) peel. Biosci Biotechnol Biochem 70, 999\u20131002, doi: 10.1271\/bbb.70.999 (2006).","journal-title":"Biosci Biotechnol Biochem"},{"key":"BFsrep46449_CR19","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1016\/j.fct.2006.06.014","volume":"44","author":"JS Lee","year":"2006","unstructured":"Lee, J. S. et al. Supplementation of whole persimmon leaf improves lipid profiles and suppresses body weight gain in rats fed high-fat diet. Food Chem Toxicol 44, 1875\u20131883, doi: 10.1016\/j.fct.2006.06.014 (2006).","journal-title":"Food Chem Toxicol"},{"key":"BFsrep46449_CR20","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1089\/jmf.2014.3307","volume":"18","author":"R Ryu","year":"2015","unstructured":"Ryu, R. et al. Ethanol Extract of Persimmon Tree Leaves Improves Blood Circulation and Lipid Metabolism in Rats Fed a High-Fat Diet. J Med Food 18, 715\u2013723, doi: 10.1089\/jmf.2014.3307 (2015).","journal-title":"J Med Food"},{"key":"BFsrep46449_CR21","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.jep.2015.01.007","volume":"163","author":"C Xie","year":"2015","unstructured":"Xie, C., Xie, Z., Xu, X. & Yang, D. Persimmon (Diospyros kaki L.) leaves: a review on traditional uses, phytochemistry and pharmacological properties. J Ethnopharmacol 163, 229\u2013240, doi: 10.1016\/j.jep.2015.01.007 (2015).","journal-title":"J Ethnopharmacol"},{"key":"BFsrep46449_CR22","doi-asserted-by":"crossref","unstructured":"Age-Related Eye Disease Study Research, G. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. 9. Archives of ophthalmology 119, 1439\u20131452 (2001).","DOI":"10.1001\/archopht.119.10.1439"},{"key":"BFsrep46449_CR23","doi-asserted-by":"crossref","unstructured":"Age-Related Eye Disease Study Research, G. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Archives of ophthalmology 119, 1417\u20131436 (2001).","DOI":"10.1001\/archopht.119.10.1417"},{"key":"BFsrep46449_CR24","doi-asserted-by":"publisher","first-page":"7750","DOI":"10.1021\/acs.jafc.5b02578","volume":"63","author":"KA Kim","year":"2015","unstructured":"Kim, K. A. et al. Leaves of Persimmon (Diospyros kaki Thunb.) Ameliorate N-Methyl-N-nitrosourea (MNU)-Induced Retinal Degeneration in Mice. Journal of agricultural and food chemistry 63, 7750\u20137759, doi: 10.1021\/acs.jafc.5b02578 (2015).","journal-title":"Journal of agricultural and food chemistry"},{"key":"BFsrep46449_CR25","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.fct.2013.02.052","volume":"56","author":"H Jo","year":"2013","unstructured":"Jo, H., Choi, S. J. & Jung, S. H. Protective effects of a compound isolated from Alnus japonica on oxidative stress-induced death in transformed retinal ganglion cells. Food Chem Toxicol 56, 425\u2013435, doi: 10.1016\/j.fct.2013.02.052 (2013).","journal-title":"Food Chem Toxicol"},{"key":"BFsrep46449_CR26","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.neuint.2012.01.015","volume":"60","author":"NN Osborne","year":"2012","unstructured":"Osborne, N. N., Ji, D., Majid, A. S., Del Soldata, P. & Sparatore, A. Glutamate oxidative injury to RGC-5 cells in culture is necrostatin sensitive and blunted by a hydrogen sulfide (H2S)-releasing derivative of aspirin (ACS14). Neurochemistry international 60, 365\u2013378, doi: 10.1016\/j.neuint.2012.01.015 (2012).","journal-title":"Neurochemistry international"},{"key":"BFsrep46449_CR27","doi-asserted-by":"publisher","first-page":"L1515","DOI":"10.1152\/ajplung.00252.2006","volume":"292","author":"JL Aschner","year":"2007","unstructured":"Aschner, J. L. et al. Heat shock protein 90 modulates endothelial nitric oxide synthase activity and vascular reactivity in the newborn piglet pulmonary circulation. Am J Physiol Lung Cell Mol Physiol 292, L1515\u20131525, doi: 00252.2006 [pii]10.1152\/ajplung.00252.2006 (2007).","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"BFsrep46449_CR28","doi-asserted-by":"publisher","first-page":"1828","DOI":"10.1007\/s11064-010-0249-5","volume":"35","author":"KD Kang","year":"2010","unstructured":"Kang, K. D. et al. Sulbutiamine Counteracts Trophic Factor Deprivation Induced Apoptotic Cell Death in Transformed Retinal Ganglion Cells. Neurochem Res 35, 1828\u20131839, doi: 10.1007\/s11064-010-0249-5 (2010).","journal-title":"Neurochem Res"},{"key":"BFsrep46449_CR29","doi-asserted-by":"publisher","first-page":"5151","DOI":"10.1167\/Iovs.02-1101","volume":"44","author":"J Danias","year":"2003","unstructured":"Danias, J. et al. Quantitative analysis of retinal ganglion cell (RGC) loss in aging DBA\/2NNia glaucomatous mice: Comparison with RGC loss in aging C57\/BL6 mice. Investigative ophthalmology & visual science 44, 5151\u20135162, doi:Doi 10.1167\/Iovs.02-1101 (2003).","journal-title":"Investigative ophthalmology & visual science"},{"key":"BFsrep46449_CR30","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1161\/01.STR.0000247942.42349.37","volume":"38","author":"L Annunziato","year":"2007","unstructured":"Annunziato, L., Cataldi, M., Pignataro, G., Secondo, A. & Molinaro, P. Glutamate-independent calcium toxicity: introduction. Stroke; a journal of cerebral circulation 38, 661\u2013664, doi: 10.1161\/01.STR.0000247942.42349.37 (2007).","journal-title":"Stroke; a journal of cerebral circulation"},{"key":"BFsrep46449_CR31","doi-asserted-by":"publisher","first-page":"4267","DOI":"10.1167\/iovs.09-3484","volume":"50","author":"NJ Van Bergen","year":"2009","unstructured":"Van Bergen, N. J. et al. Recharacterization of the RGC-5 Retinal Ganglion Cell Line. Investigative ophthalmology & visual science 50, 4267\u20134272, doi: 10.1167\/iovs.09-3484 (2009).","journal-title":"Investigative ophthalmology & visual science"},{"key":"BFsrep46449_CR32","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1039\/c4pp00456f","volume":"14","author":"P Zhang","year":"2015","unstructured":"Zhang, P., Huang, C., Wang, W. & Wang, M. Early changes in staurosporine-induced differentiated RGC-5 cells indicate cellular injury response to nonlethal blue light exposure. Photochemical & photobiological sciences: Official journal of the European Photochemistry Association and the European Society for Photobiology 14, 1093\u20131099, doi: 10.1039\/c4pp00456f (2015).","journal-title":"Photochemical & photobiological sciences: Official journal of the European Photochemistry Association and the European Society for Photobiology"},{"key":"BFsrep46449_CR33","doi-asserted-by":"crossref","unstructured":"Thompson, A. F., Crowe, M. E., Lieven, C. J. & Levin, L. A. Induction of Neuronal Morphology in the 661W Cone Photoreceptor Cell Line with Staurosporine. Plos One 10, doi: ARTN e014527010.1371\/journal.pone.0145270 (2015).","DOI":"10.1371\/journal.pone.0145270"},{"key":"BFsrep46449_CR34","doi-asserted-by":"publisher","first-page":"5712","DOI":"10.1167\/iovs.13-12085","volume":"54","author":"RR Krishnamoorthy","year":"2013","unstructured":"Krishnamoorthy, R. R., Clark, A. F., Daudt, D., Vishwanatha, J. K. & Yorio, T. A Forensic Path to RGC-5 Cell Line Identification: Lessons Learned. Investigative ophthalmology & visual science 54, 5712\u20135719, doi: 10.1167\/iovs.13-12085 (2013).","journal-title":"Investigative ophthalmology & visual science"},{"key":"BFsrep46449_CR35","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.exer.2013.10.012","volume":"119","author":"MR Al-Ubaidi","year":"2014","unstructured":"Al-Ubaidi, M. R. RGC-5: are they really 661W? The saga continues. Exp Eye Res 119, 115, doi: 10.1016\/j.exer.2013.10.012 (2014).","journal-title":"Exp Eye Res"},{"key":"BFsrep46449_CR36","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/978-1-4614-3209-8_19","volume":"801","author":"C Sippl","year":"2014","unstructured":"Sippl, C. & Tamm, E. R. What Is the Nature of the RGC-5 Cell Line? Adv Exp Med Biol 801, 145\u2013154, doi: 10.1007\/978-1-4614-3209-8_19 (2014).","journal-title":"Adv Exp Med Biol"},{"key":"BFsrep46449_CR37","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s002040050381","volume":"71","author":"JH Kuo","year":"1997","unstructured":"Kuo, J. H., Chen, H. W., Chou, R. G. & Lii, C. K. Vitamin E protection of cell morphology under oxidative stress is related to cytoskeletal proteins in rat hepatocytes. Arch Toxicol 71, 231\u2013237 (1997).","journal-title":"Arch Toxicol"},{"key":"BFsrep46449_CR38","doi-asserted-by":"publisher","first-page":"7 2","DOI":"10.1002\/0471142956.cy0702s52","volume":"7","author":"Z Darzynkiewicz","year":"2010","unstructured":"Darzynkiewicz, Z. Critical aspects in analysis of cellular DNA content. Curr Protoc Cytom Chapter 7, Unit 7 2, doi: 10.1002\/0471142956.cy0702s52 (2010).","journal-title":"Curr Protoc Cytom"},{"key":"BFsrep46449_CR39","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.neuint.2010.08.005","volume":"57","author":"SH Jung","year":"2010","unstructured":"Jung, S. H., Kim, B. J., Lee, E. H. & Osborne, N. N. Isoquercitrin is the most effective antioxidant in the plant Thuja orientalis and able to counteract oxidative-induced damage to a transformed cell line (RGC-5 cells). Neurochem Int 57, 713\u2013721, doi: 10.1016\/j.neuint.2010.08.005 (2010).","journal-title":"Neurochem Int"},{"key":"BFsrep46449_CR40","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.freeradbiomed.2013.10.816","volume":"67","author":"R Michalski","year":"2014","unstructured":"Michalski, R., Michalowski, B., Sikora, A., Zielonka, J. & Kalyanaraman, B. On the use of fluorescence lifetime imaging and dihydroethidium to detect superoxide in intact animals and ex vivo tissues: a reassessment. Free Radic Biol Med 67, 278\u2013284, doi: 10.1016\/j.freeradbiomed.2013.10.816 (2014).","journal-title":"Free Radic Biol Med"},{"key":"BFsrep46449_CR41","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1080\/10715760701297354","volume":"41","author":"HM Peshavariya","year":"2007","unstructured":"Peshavariya, H. M., Dusting, G. J. & Selemidis, S. Analysis of dihydroethidium fluorescence for the detection of intracellular and extracellular superoxide produced by NADPH oxidase. Free Radic Res 41, 699\u2013712, doi: 10.1080\/10715760701297354 (2007).","journal-title":"Free Radic Res"},{"key":"BFsrep46449_CR42","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1089\/152308604322899350","volume":"6","author":"R Sharma","year":"2004","unstructured":"Sharma, R., Yang, Y., Sharma, A., Awasthi, S. & Awasthi, Y. C. Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxid Redox Signal 6, 289\u2013300, doi: 10.1089\/152308604322899350 (2004).","journal-title":"Antioxid Redox Signal"},{"key":"BFsrep46449_CR43","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.taap.2015.10.006","volume":"289","author":"SS Singhal","year":"2015","unstructured":"Singhal, S. S. et al. Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling. Toxicol Appl Pharmacol 289, 361\u2013370, doi: 10.1016\/j.taap.2015.10.006 (2015).","journal-title":"Toxicol Appl Pharmacol"},{"key":"BFsrep46449_CR44","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1021\/bi048016f","volume":"44","author":"A Maeda","year":"2005","unstructured":"Maeda, A., Crabb, J. W. & Palczewski, K. Microsomal glutathione S-transferase 1 in the retinal pigment epithelium: protection against oxidative stress and a potential role in aging. Biochemistry 44, 480\u2013489, doi: 10.1021\/bi048016f (2005).","journal-title":"Biochemistry"},{"key":"BFsrep46449_CR45","doi-asserted-by":"publisher","first-page":"8726","DOI":"10.1523\/JNEUROSCI.2774-04.2004","volume":"24","author":"D Fischer","year":"2004","unstructured":"Fischer, D., Petkova, V., Thanos, S. & Benowitz, L. I. Switching mature retinal ganglion cells to a robust growth state in vivo: gene expression and synergy with RhoA inactivation. J Neurosci 24, 8726\u20138740, doi: 10.1523\/JNEUROSCI.2774-04.2004 (2004).","journal-title":"J Neurosci"},{"key":"BFsrep46449_CR46","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1016\/j.freeradbiomed.2006.01.012","volume":"41","author":"RA Kowluru","year":"2006","unstructured":"Kowluru, R. A., Kowluru, V., Xiong, Y. & Ho, Y. S. Overexpression of mitochondrial superoxide dismutase in mice protects the retina from diabetes-induced oxidative stress. Free Radic Biol Med 41, 1191\u20131196, doi: 10.1016\/j.freeradbiomed.2006.01.012 (2006).","journal-title":"Free Radic Biol Med"},{"key":"BFsrep46449_CR47","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1097\/00006982-199212010-00012","volume":"12","author":"H Yamashita","year":"1992","unstructured":"Yamashita, H., Horie, K., Yamamoto, T., Nagano, T. & Hirano, T. Light-induced retinal damage in mice. Hydrogen peroxide production and superoxide dismutase activity in retina. Retina 12, 59\u201366 (1992).","journal-title":"Retina"},{"key":"BFsrep46449_CR48","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1515\/BC.2003.064","volume":"384","author":"Y Miyamoto","year":"2003","unstructured":"Miyamoto, Y. et al. Oxidative stress caused by inactivation of glutathione peroxidase and adaptive responses. Biol Chem 384, 567\u2013574, doi: 10.1515\/BC.2003.064 (2003).","journal-title":"Biol Chem"},{"key":"BFsrep46449_CR49","doi-asserted-by":"crossref","first-page":"549","DOI":"10.33549\/physiolres.932041","volume":"60","author":"N Lekic","year":"2011","unstructured":"Lekic, N. et al. Differential oxidative stress responses to D-galactosamine-lipopolysaccharide hepatotoxicity based on real time PCR analysis of selected oxidant\/antioxidant and apoptotic gene expressions in rat. Physiol Res 60, 549\u2013558 (2011).","journal-title":"Physiol Res"},{"key":"BFsrep46449_CR50","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.bbabio.2008.03.015","volume":"1777","author":"V Subramaniam","year":"2008","unstructured":"Subramaniam, V. et al. MITOCHIP assessment of differential gene expression in the skeletal muscle of Ant1 knockout mice: coordinate regulation of OXPHOS, antioxidant, and apoptotic genes. Biochim Biophys Acta 1777, 666\u2013675, doi: 10.1016\/j.bbabio.2008.03.015 (2008).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep46449_CR51","doi-asserted-by":"publisher","first-page":"22932","DOI":"10.1074\/jbc.274.33.22932","volume":"274","author":"AH Boulares","year":"1999","unstructured":"Boulares, A. H. et al. Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells. The Journal of biological chemistry 274, 22932\u201322940 (1999).","journal-title":"The Journal of biological chemistry"},{"key":"BFsrep46449_CR52","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1080\/02713680590956306","volume":"30","author":"X Zhang","year":"2005","unstructured":"Zhang, X. et al. Apoptosis and cell proliferation in proliferative retinal disorders: PCNA, Ki-67, caspase-3, and PARP expression. Curr Eye Res 30, 395\u2013403, doi: 10.1080\/02713680590956306 (2005).","journal-title":"Curr Eye Res"},{"key":"BFsrep46449_CR53","first-page":"21","volume":"3","author":"Y Ma","year":"2011","unstructured":"Ma, Y., Chen, H., Xia, W. & Ying, W. Oxidative stress and PARP activation mediate the NADH-induced decrease in glioma cell survival. Int J Physiol Pathophysiol Pharmacol 3, 21\u201328 (2011).","journal-title":"Int J Physiol Pathophysiol Pharmacol"},{"key":"BFsrep46449_CR54","doi-asserted-by":"publisher","first-page":"5611","DOI":"10.1111\/j.1742-4658.2007.06083.x","volume":"274","author":"J Rajawat","year":"2007","unstructured":"Rajawat, J., Vohra, I., Mir, H. A., Gohel, D. & Begum, R. Effect of oxidative stress and involvement of poly(ADP-ribose) polymerase (PARP) in Dictyostelium discoideum development. FEBS J 274, 5611\u20135618, doi: 10.1111\/j.1742-4658.2007.06083.x (2007).","journal-title":"FEBS J"},{"key":"BFsrep46449_CR55","doi-asserted-by":"publisher","first-page":"3435","DOI":"10.2337\/diabetes.54.12.3435","volume":"54","author":"IG Obrosova","year":"2005","unstructured":"Obrosova, I. G. et al. Oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in experimental diabetic neuropathy: the relation is revisited. Diabetes 54, 3435\u20133441 (2005).","journal-title":"Diabetes"},{"key":"BFsrep46449_CR56","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1038\/sj.cdd.4401105","volume":"9","author":"M Donovan","year":"2002","unstructured":"Donovan, M. & Cotter, T. G. Caspase-independent photoreceptor apoptosis in vivo and differential expression of apoptotic protease activating factor-1 and caspase-3 during retinal development. Cell Death Differ 9, 1220\u20131231, doi: 10.1038\/sj.cdd.4401105 (2002).","journal-title":"Cell Death Differ"},{"key":"BFsrep46449_CR57","doi-asserted-by":"publisher","first-page":"4465","DOI":"10.1111\/j.1582-4934.2008.00545.x","volume":"13","author":"L Kupcsik","year":"2009","unstructured":"Kupcsik, L., Meurya, T., Flury, M., Stoddart, M. & Alini, M. Statin-induced calcification in human mesenchymal stem cells is cell death related. J Cell Mol Med 13, 4465\u20134473, doi: 10.1111\/j.1582-4934.2008.00545.x (2009).","journal-title":"J Cell Mol Med"},{"key":"BFsrep46449_CR58","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1038\/sj.eye.6701576","volume":"18","author":"H Levkovitch-Verbin","year":"2004","unstructured":"Levkovitch-Verbin, H. Animal models of optic nerve diseases. Eye 18, 1066\u20131074, doi: 10.1038\/sj.eye.6701576 (2004).","journal-title":"Eye"},{"key":"BFsrep46449_CR59","doi-asserted-by":"publisher","first-page":"244","DOI":"10.3171\/jns.1989.71.2.0244","volume":"71","author":"TA Gennarelli","year":"1989","unstructured":"Gennarelli, T. A. et al. Axonal injury in the optic nerve: a model simulating diffuse axonal injury in the brain. Journal of neurosurgery 71, 244\u2013253, doi: 10.3171\/jns.1989.71.2.0244 (1989).","journal-title":"Journal of neurosurgery"},{"key":"BFsrep46449_CR60","doi-asserted-by":"publisher","first-page":"401","DOI":"10.3892\/etm.2012.619","volume":"4","author":"HB Tan","year":"2012","unstructured":"Tan, H. B. et al. Evaluation of a partial optic nerve crush model in rats. Experimental and therapeutic medicine 4, 401\u2013404, doi: 10.3892\/etm.2012.619 (2012).","journal-title":"Experimental and therapeutic medicine"},{"key":"BFsrep46449_CR61","doi-asserted-by":"crossref","unstructured":"Fischer, A. H., Jacobson, K. A., Rose, J. & Zeller, R. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc 2008, pdb prot4986, doi: 10.1101\/pdb.prot4986 (2008).","DOI":"10.1101\/pdb.prot4986"},{"key":"BFsrep46449_CR62","first-page":"183","volume":"88","author":"J Lawry","year":"2004","unstructured":"Lawry, J. Detection of apoptosis by the TUNEL assay. Methods Mol Med 88, 183\u2013190 (2004).","journal-title":"Methods Mol Med"},{"key":"BFsrep46449_CR63","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/978-1-61779-108-6_16","volume":"740","author":"WK Ju","year":"2011","unstructured":"Ju, W. K. & Kim, K. Y. Measuring glutamate receptor activation-induced apoptotic cell death in ischemic rat retina using the TUNEL assay. Methods Mol Biol 740, 149\u2013156, doi: 10.1007\/978-1-61779-108-6_16 (2011).","journal-title":"Methods Mol Biol"},{"key":"BFsrep46449_CR64","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.exer.2009.02.015","volume":"89","author":"G Parrilla-Reverter","year":"2009","unstructured":"Parrilla-Reverter, G. et al. Effects of different neurotrophic factors on the survival of retinal ganglion cells after a complete intraorbital nerve crush injury: a quantitative in vivo study. Experimental eye research 89, 32\u201341, doi: 10.1016\/j.exer.2009.02.015 (2009).","journal-title":"Experimental eye research"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep46449.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep46449","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/srep46449","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/srep46449.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T17:52:57Z","timestamp":1671817977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep46449"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,20]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,6,16]]}},"alternative-id":["BFsrep46449"],"URL":"https:\/\/doi.org\/10.1038\/srep46449","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,20]]},"assertion":[{"value":"26 May 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"46449"}}