{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:12:01Z","timestamp":1791396721205,"version":"4.3.3"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,11,28]],"date-time":"2015-11-28T00:00:00Z","timestamp":1448668800000},"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":[[2016,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Although a variety of animal models have been used to test drug candidates and examine the pathogenesis of diabetic retinopathy, time\u2010saving and inexpensive models are still needed to evaluate the increasing number of therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      We developed a model for diabetic retinopathy using the early stage of transgenic zebrafish (\n                      <jats:italic>flk<\/jats:italic>\n                      :EGFP) by treating embryos with 130\u2009mM glucose, from 3\u20106 days post fertilisation (high\u2010glucose model). On day 6, lenses from zebrafish larvae were isolated and treated with 3% trypsin, and changes in hyaloid\u2010retinal vessels were analysed using fluorescent stereomicroscopy. In addition, expression of tight junction proteins (such as zonula occludens\u20101), effects of hyperosmolar solutions and of hypoxia, and\n                      <jats:italic>Vegf<\/jats:italic>\n                      expression were assessed by RT \u2013PCR. NO production was assessed with a fluorescent substrate. Effects of inhibitors of the VEGF receptor, NO synthesis and a VEGF antibody (ranibizumab) were also measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      In this high\u2010glucose model, dilation of hyaloid\u2010retinal vessels, on day 6, was accompanied by morphological lesions with disruption of tight junction proteins, overproduction of\n                      <jats:italic>Vegf<\/jats:italic>\n                      mRNA and increased NO production. Treatment of this high\u2010glucose model with an inhibitor of VEGF receptor tyrosine kinase or an inhibitor of NO synthase or ranibizumab decreased dilation of hyaloid\u2010retinal vessels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>These findings suggest that short\u2010term exposure of zebrafish larvae to high\u2010glucose conditions could be used for screening and drug discovery for diabetic retinopathy and particularly for disorders of retinal vessels related to disruption of tight junction proteins and excessive VEGF and NO production.<\/jats:p>\n                  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