{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:47:12Z","timestamp":1787312832709,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,2,27]],"date-time":"2014-02-27T00:00:00Z","timestamp":1393459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["RO1-EY-022408"],"award-info":[{"award-number":["RO1-EY-022408"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,3]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n Retinal neurodegeneration is an early and critical event in several diseases associated with blindness. Clinically, therapies that target neurodegeneration fail. We aimed to elucidate the multiple roles by which thioredoxin\u2010interacting protein (\n TXNIP<\/jats:styled-content>\n ) contributes to initial and sustained retinal neurodegeneration.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n Neurotoxicity was induced by intravitreal injection of\n NMDA<\/jats:styled-content>\n into wild\u2010type (\n WT<\/jats:styled-content>\n ) and\n TXNIP<\/jats:styled-content>\n \u2010knockout (\n TKO<\/jats:styled-content>\n ) mice. The expression of apoptotic and inflammatory markers was assessed by immunohistochemistry,\n elisa<\/jats:sc>\n and Western blot. Microvascular degeneration was assessed by periodic acid\u2010Schiff and haematoxylin staining and retinal function by electroretinogram.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n NMDA<\/jats:styled-content>\n induced early (1 day) and significant retinal\n PARP<\/jats:styled-content>\n activation, a threefold increase in\n TUNEL<\/jats:styled-content>\n \u2010positive nuclei and 40% neuronal loss in ganglion cell layer (\n GCL<\/jats:styled-content>\n ); and vascular permeability in\n WT<\/jats:styled-content>\n but not\n TKO<\/jats:styled-content>\n mice.\n NMDA<\/jats:styled-content>\n induced glial activation, expression of\n TNF<\/jats:styled-content>\n \u2010\u03b1 and\n IL<\/jats:styled-content>\n \u20101\u03b2 that co\u2010localized with\n M<\/jats:styled-content>\n \u00fcller cells in\n WT<\/jats:styled-content>\n but not\n TKO<\/jats:styled-content>\n mice. In parallel,\n NMDA<\/jats:styled-content>\n triggered the expression of\n NOD<\/jats:styled-content>\n \u2010like receptor protein (\n NLRP3<\/jats:styled-content>\n ), activation of caspase\u20101, and release of\n IL<\/jats:styled-content>\n \u20101\u03b2 and\n TNF<\/jats:styled-content>\n \u2010\u03b1 in primary\n WT<\/jats:styled-content>\n but not\n TKO<\/jats:styled-content>\n M\u00fcller cultures. After 14 days,\n NMDA<\/jats:styled-content>\n induced 1.9\u2010fold microvascular degeneration, 60% neuronal loss in\n GCL<\/jats:styled-content>\n and increased\n TUNEL<\/jats:styled-content>\n \u2010labelled cells in the\n GCL<\/jats:styled-content>\n and inner nuclear layer in\n WT<\/jats:styled-content>\n but not\n TKO<\/jats:styled-content>\n mice. Electroretinogram analysis showed more significant reductions in b\u2010wave amplitudes in\n WT<\/jats:styled-content>\n than in\n TKO<\/jats:styled-content>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion and Implications<\/jats:title>\n \n Targeting\n TXNIP<\/jats:styled-content>\n expression prevented early retinal ganglion cell death, glial activation, retinal inflammation and secondary neuro\/microvascular degeneration and preserved retinal function. TXNIP is a promising new therapeutic target for retinal neurodegenerative diseases.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.12535","type":"journal-article","created":{"date-parts":[[2013,11,28]],"date-time":"2013-11-28T00:05:03Z","timestamp":1385597103000},"page":"1299-1313","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Deletion of thioredoxin\u2010interacting protein preserves retinal neuronal function by preventing inflammation and vascular injury"],"prefix":"10.1111","volume":"171","author":[{"given":"M F","family":"El\u2010Azab","sequence":"first","affiliation":[{"name":"Center for Pharmacy and Experimental Therapeutics University of Georgia Augusta GA USA"},{"name":"James and Jean Culver Vision Discovery Institute Georgia Regents University Augusta GA USA"},{"name":"Charlie Norwood Veterans Affairs Medical Center Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B R B","family":"Baldowski","sequence":"additional","affiliation":[{"name":"Center for Pharmacy and Experimental Therapeutics University of Georgia Augusta GA USA"},{"name":"James and Jean Culver Vision Discovery Institute Georgia Regents University Augusta GA USA"},{"name":"Charlie Norwood Veterans Affairs Medical Center Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B A","family":"Mysona","sequence":"additional","affiliation":[{"name":"Center for Pharmacy and Experimental Therapeutics University of Georgia Augusta GA USA"},{"name":"James and Jean Culver Vision Discovery Institute Georgia Regents University Augusta GA USA"},{"name":"Charlie Norwood Veterans Affairs Medical Center Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A Y","family":"Shanab","sequence":"additional","affiliation":[{"name":"Center for Pharmacy and Experimental Therapeutics University of Georgia Augusta GA USA"},{"name":"James and Jean Culver Vision Discovery Institute Georgia Regents University Augusta GA USA"},{"name":"Charlie Norwood Veterans Affairs Medical Center Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I N","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Center for Pharmacy and Experimental Therapeutics University of Georgia Augusta GA USA"},{"name":"James and Jean Culver Vision Discovery Institute Georgia Regents University Augusta GA USA"},{"name":"Charlie Norwood Veterans Affairs Medical Center Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Abdelsaid","sequence":"additional","affiliation":[{"name":"Center for Pharmacy and Experimental Therapeutics University of Georgia Augusta GA USA"},{"name":"James and Jean Culver Vision Discovery Institute Georgia Regents University Augusta GA USA"},{"name":"Charlie Norwood Veterans Affairs Medical Center Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Matragoon","sequence":"additional","affiliation":[{"name":"Center for Pharmacy and Experimental Therapeutics University of Georgia Augusta GA USA"},{"name":"James and Jean Culver Vision Discovery Institute Georgia Regents University Augusta GA USA"},{"name":"Charlie Norwood Veterans Affairs Medical Center Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K E","family":"Bollinger","sequence":"additional","affiliation":[{"name":"James and Jean Culver Vision Discovery Institute Georgia Regents University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Saul","sequence":"additional","affiliation":[{"name":"James and Jean Culver Vision Discovery Institute Georgia Regents University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A B","family":"El\u2010Remessy","sequence":"additional","affiliation":[{"name":"Center for Pharmacy and Experimental Therapeutics University of Georgia Augusta GA USA"},{"name":"James and Jean Culver Vision Discovery Institute Georgia Regents University Augusta GA USA"},{"name":"Charlie Norwood Veterans Affairs Medical Center Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.157941"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4761"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.091289"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01336.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1669"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1935-1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06705.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.07.034"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5173(02)00056-X"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2009.07.001"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-11-04427.1992"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICU.0b013e32834372ec"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/438238"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.163.6.1433"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2078"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63558-4"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900173"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04065.x"},{"key":"e_1_2_8_20_1","first-page":"414","article-title":"ATP release and purinergic signaling in NLRP3 inflammasome activation","volume":"3","author":"Gombault A","year":"2012","journal-title":"Front Immunol"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800293105"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/162.1.215"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.148676"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03871.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2007\/95103"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.1473"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.11.034"},{"key":"e_1_2_8_28_1","first-page":"2391","article-title":"N\u2010methyl\u2010D\u2010aspartate (NMDA)\u2010induced apoptosis in rat retina","volume":"40","author":"Lam TT","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2011.161"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00873.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02664"},{"key":"e_1_2_8_32_1","first-page":"2993","article-title":"Electroporation\u2010mediated gene delivery of cleavage\u2010resistant pro\u2010nerve growth factor causes retinal neuro\u2010 and vascular degeneration","volume":"18","author":"Matragoon S","year":"2012","journal-title":"Mol Vis"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-1716"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2008.126"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-008-0742-1"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.06.026"},{"key":"e_1_2_8_37_1","first-page":"1060","article-title":"Mechanism of N\u2010methyl\u2010D\u2010aspartate\u2010induced retinal ganglion cell death","volume":"113","author":"Nakazawa T","year":"2009","journal-title":"Nippon Ganka Gakkai Zasshi"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.2008.01459.x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(99)00044-2"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21852"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00288"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.2174\/157015908784533851"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1184003"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2012.07.020"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4102"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.156612"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4137"},{"key":"e_1_2_8_48_1","first-page":"523","article-title":"Advanced glycation end products (AGEs) co\u2010localize with AGE receptors in the retinal vasculature of diabetic and of AGE\u2010infused rats","volume":"150","author":"Stitt AW","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00265.2011"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-013-0017-5"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2022"},{"key":"e_1_2_8_52_1","first-page":"300","article-title":"Alteration of growth factors and neuronal death in diabetic retinopathy: what we have learned so far","volume":"17","author":"Whitmire W","year":"2011","journal-title":"Mol Vis"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0510"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.12535","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.12535","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T15:26:46Z","timestamp":1694618806000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.12535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,27]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,3]]}},"alternative-id":["10.1111\/bph.12535"],"URL":"https:\/\/doi.org\/10.1111\/bph.12535","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,27]]},"assertion":[{"value":"2013-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-11-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-02-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}