title: Integrin-linked kinase inhibition attenuates permeability of the streptozotocin-induced diabetic rat retina.
abstract: Integrin-linked kinase (ILK), as a multi-functional regulator, has been associated with diabetic retinopathy (DR). In this study, we investigated whether inhibition of ILK could result in therapeutic effects. Diabetes mellitus's rats were induced by streptozotocin (STZ) injection. After 1 weeks induction, rats were injected intraperitoneally daily with ILK inhibitor, QLT0267, at 5 mg/kg. Then, the rats were examined by 4, 8, and 12 weeks after first STZ injection. We found that QLT0267 treatment could not only lower ILK level in retina at as early as 3 weeks after the onset of diabetes but also attenuate retina permeability, which was measured by Evan's blue. Maximum effect was found in 11 weeks treatment. Meanwhile, QLT0267 did not disturbed blood glucose concentration. Furthermore, QLT0267 inhibited Akt (Ser473) activation and reduced expression of HIF1α and VEGF which were evaluated by western blot, real time PCR, and immunohistochemistry. We conclude that ILK may be a new target for DR.
authors.affiliation: Department of Ophthalmology, Tangdu Hospital, The Fourth Military Medical University of PLA, Xian, People's Republic of China, fmmuliyjun@gmail.com.
authors.forename: Yangjun
authors.initials: Y
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D010539:Permeability / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D013311:Streptozocin / Q000633:toxicity; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D001391:Azo Compounds; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011720:Pyrazoles; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A; D000099200:Scaffold Protein ILK; C497444:Hif1a protein, rat; C552362:QLT 0267