{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:12:54Z","timestamp":1791267174921,"version":"4.1.0"},"reference-count":67,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Early retinal neurodegeneration occurs as one of the complications of diabetes even before clinically detectable diabetic vascular retinopathy. The pathogenesis of retinal diabetic neuropathy is still not well understood. We investigated the serial changes or fluctuations in intraocular pressure (IOP) and examined their roles in the pathogenesis of neuronal degeneration in diabetic retina.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Male Sprague Dawley rats with streptozotocin\u2010induced diabetes were treated with ophthalmic preparations of brinzolamide, latanoprost, both drugs (combined treatment) or saline for 8 weeks. IOP was measured daily under general anaesthesia using a rebound tonometer. Antegrade axoplasmic flow in the optic nerve was assessed with a fluorescent substrate. Immunohistochemical staining, TUNEL assays and western blots were also used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The fluctuation of IOP was higher in the diabetes group than in the normal control or the combined treatment group. Diabetes\u2010induced apoptosis of retinal ganglion cells was decreased by combined treatment. Increased expression of glial fibrillary acidic protein or Iba\u20101 in the retina or optic nerve head, induced by diabetes, was attenuated only by the combined treatment. Intercellular adhesion molecule\u20101 was increased in diabetic rats but not in the combined treatment group. Diabetes\u2010induced loss of antegrade axoplasmic transport was partially relieved with combined treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Elevated IOP fluctuations seemed to be associated with the gliosis, neuroinflammation, and neurodegeneration induced by diabetes. The loss of retinal ganglion cells might be relieved by IOP\u2010lowering medication. The improvement of unstable perfusion pressure could play a role in neuroprotection in the diabetic retina.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15033","type":"journal-article","created":{"date-parts":[[2020,2,22]],"date-time":"2020-02-22T22:32:25Z","timestamp":1582410745000},"page":"3046-3059","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Intraocular pressure fluctuation and neurodegeneration in the diabetic rat retina"],"prefix":"10.1111","volume":"177","author":[{"given":"Kyoung In","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Eun","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Kee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14748"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14752"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1005073"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2425"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2038"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-7263"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2009.07.001"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2007.10.031"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2015.11.031"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)62124-3"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.06.005"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2015.01.001"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2008.08.006"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2014.07.001"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-21031"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-5041"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.2000.0975"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-19988"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2012.09.005"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.09.018"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003-0027"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(02)00008-3"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3928\/01913913-20100420-02"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/705783"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28985-8"},{"key":"e_1_2_11_30_1","first-page":"3415","article-title":"Effect of general anesthetics on IOP in rats with experimental aqueous outflow obstruction","volume":"41","author":"Jia L.","year":"2000","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5212"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.203067"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2008.11.012"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2007.128819"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.156695"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.4103\/jovr.jovr_35_18"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2010.09.004"},{"key":"e_1_2_11_39_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/9216791","article-title":"Intravitreal bevacizumab injection attenuates diabetic retinopathy in adult rats with experimentally induced diabetes in the early stage","volume":"2018","author":"Lv J.","year":"2018","journal-title":"Journal Diabetes Research"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12955"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2006.05.018"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02213.x"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2010.191841"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.02.016"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1177-6"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(14)74550-7"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1253"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2156273"},{"key":"e_1_2_11_49_1","first-page":"170","article-title":"Effect of high glucose on fibronectin expression and cell proliferation in trabecular meshwork cells","volume":"43","author":"Sato T.","year":"2002","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2004.052860"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2013.09.005"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.2337\/db18-0682"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-018-4692-1"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.70.6.456"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1522014113"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107291"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2015.08.001"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167364"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1097\/IJG.0000000000000517"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2000.tb00079.x"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.10.031"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.64.11.845"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1444-0938.2010.00546.x"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2011.06.022"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9814"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.07.051"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-011-9653-x"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0734-9"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.15033","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15033","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.15033","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T11:59:51Z","timestamp":1693742391000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.15033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,15]]},"references-count":67,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1111\/bph.15033"],"URL":"https:\/\/doi.org\/10.1111\/bph.15033","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,15]]},"assertion":[{"value":"2019-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}