title: Suppression of protein kinase C-ζ attenuates vascular leakage via prevention of tight junction protein decrease in diabetic retinopathy.
abstract: To investigate the effect of protein kinase C (PKC)-ζ inhibition on vascular leakage in diabetic retinopathy, streptozotocin-induced diabetic mice were intravitreously injected with siPKC-ζ. According to the fluorescein angiography of the retinal vessels, suppression of PKC-ζ effectively attenuated vascular leakage in diabetic retina. Further evaluation on the retina with western blot analysis and immunohistochemistry revealed accompanying restoration of tight junction proteins on retinal vessels. As two major contributors to vascular leakage in diabetic retinopathy, vascular endothelial growth factor (VEGF) and advanced glycation end products (AGEs) were investigated on the tight junction protein expression in endothelial cells. Inhibition of PKC-ζ attenuated VEGF-induced decrease of tight junction proteins and accompanying hyperpermeability in human retinal microvascular endothelial cells (HRMECs). PKC-ζ inhibition also attenuated AGE-induced decrease of tight junction proteins in HRMECs. Our findings suggest that inhibition of PKC-ζ could be an alternative treatment option for compromised blood-retinal barrier in diabetic retinopathy.
authors.affiliation: Fight Against Angiogenesis-Related Blindness Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea.
authors.forename: Hyun Beom
authors.initials: HB
authors.lastname: Song
authors.affiliation: Fight Against Angiogenesis-Related Blindness Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Hyoung-Oh
authors.initials: HO
authors.lastname: Jun
authors.affiliation: Fight Against Angiogenesis-Related Blindness Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Fight Against Angiogenesis-Related Blindness Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Department of Ophthalmology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Yu
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Kyu Won
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Fight Against Angiogenesis-Related Blindness Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea; Department of Ophthalmology, College of Medicine, Seoul National University, Seoul, Republic of Korea. Electronic address: steph25@snu.ac.kr.
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001813:Blood-Retinal Barrier; D002199:Capillary Permeability; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012171:Retinal Vessels / Q000378:metabolism*; D062725:Tight Junction Proteins / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099221:Protein Kinase C zeta
chemical_list: D017127:Glycation End Products, Advanced; D011493:Protein Kinase C; D034741:RNA, Small Interfering; D062725:Tight Junction Proteins; D042461:Vascular Endothelial Growth Factor A; D000099221:Protein Kinase C zeta; C467480:vascular endothelial growth factor A, mouse
keywords: Diabetic retinopathy; Protein kinase C-ζ; Tight junction protein; Vascular leakage