{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:05:31Z","timestamp":1777557931844,"version":"3.51.4"},"reference-count":48,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Diabetes and Vascular Disease Research"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:p>\n                    Using a porcine model of diabetes mellitus and hypercholesterolaemia, we previously showed that diabetes mellitus and hypercholesterolaemia is associated with a chronic increase in blood\u2013brain barrier permeability in the cerebral cortex, leading to selective binding of immunoglobulin G and deposition of amyloid-beta\n                    <jats:sub>1-42<\/jats:sub>\n                    peptide in pyramidal neurons. Treatment with Darapladib (GlaxoSmithKline, SB480848), an inhibitor of lipoprotein-associated phospholipase-A2, alleviated these effects. Here, investigation of the effects of chronic diabetes mellitus and hypercholesterolaemia on the pig retina revealed a corresponding increased permeability of the blood\u2013retina barrier coupled with a leak of plasma components into the retina, alterations in retinal architecture, selective IgG binding to neurons in the ganglion cell layer, thinning of retinal layers due to cell loss and increased glial fibrillary acidic protein expression in M\u00fcller cells, all of which were curtailed by treatment with Darapladib. These findings suggest that chronic diabetes mellitus and hypercholesterolaemia induces increased blood\u2013retina barrier permeability that may be linked to altered expression of blood\u2013retina barrier\u2013associated tight junction proteins, claudin and occludin, leading to structural changes in the retina consistent with diabetic retinopathy. Additionally, results suggest that drugs with vascular anti-inflammatory properties, such as Darapladib, may have beneficial effects on eye diseases strongly linked to vascular abnormalities such as diabetic retinopathy and age-related macular degeneration.\n                  <\/jats:p>","DOI":"10.1177\/1479164116683149","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T23:16:01Z","timestamp":1488582961000},"page":"200-213","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":46,"title":["Retinal pathology is associated with increased blood\u2013retina barrier permeability in a diabetic and hypercholesterolaemic pig model: Beneficial effects of the LpPLA\n                    <sub>2<\/sub>\n                    inhibitor Darapladib"],"prefix":"10.1177","volume":"14","author":[{"given":"Nimish K","family":"Acharya","sequence":"first","affiliation":[{"name":"Biomarker Discovery Center, New Jersey Institute for Successful Aging, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA"},{"name":"Department of Geriatrics and Gerontology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA"},{"name":"Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Qi","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University, Philadelphia, PA, USA"},{"name":"Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric L","family":"Goldwaser","sequence":"additional","affiliation":[{"name":"Biomarker Discovery Center, New Jersey Institute for Successful Aging, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA"},{"name":"Department of Geriatrics and Gerontology, School of Osteopathic Medicine, Rowan University, 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