title: Vascular changes in the developing rat retina in response to hypoxia.
abstract: This study was carried out to investigate the roles of tight junction (TJ) proteins and other factors in the increased permeability of the blood retinal barrier (BRB) affecting the immature neonatal retina following a hypoxic insult. The expression of endothelial TJ proteins such as claudin-5, occludin and zonula occludens-1 (ZO-1) and endothelial cell specific molecule-1 (ESM-1), and associated structural changes in the blood vessels were analyzed in the retinas of 1-day-old Wistar rats subjected to hypoxia for 2 h and subsequently sacrificed at different time points ranging from 3 h to 14 d. The mRNA and protein expression of claudin-5, occludin & ZO-1 was found to be reduced in the hypoxic retina, although, at the ultrastructural level, the TJ between the endothelial cells and retinal pigment epithelial cells appeared to be intact. Following the hypoxic insult vascular endothelial cells frequently showed presence of cytoplasmic vacuoles, vacuolated mitochondria and multivesicular aggregations projecting into the lumen of the capillaries. The expression of ESM-1 in the immature retinas was found to be increased following hypoxic exposure. The structural and molecular changes in the hypoxic neonatal retinas were consistent with a hypoxia induced impairment of the BRB. Hypoxia reduced the expression of TJ proteins in the neonatal retina, but the role of increased ESM-1 expression in this process warrants further investigation.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, Blk MD10, 4 Medical Drive, National University of Singapore, Singapore 117594, Singapore.
authors.forename: Gurugirijha
authors.initials: G
authors.lastname: Rathnasamy
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, Blk MD10, 4 Medical Drive, National University of Singapore, Singapore 117594, Singapore.
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Sivakumar
authors.affiliation: Singapore Eye Research Institute c/o Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore; University of Glasgow, Glasgow, Scotland G12 8QQ, UK.
authors.forename: Wallace S
authors.initials: WS
authors.lastname: Foulds
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, Blk MD10, 4 Medical Drive, National University of Singapore, Singapore 117594, Singapore.
authors.forename: Eng Ang
authors.initials: EA
authors.lastname: Ling
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, Blk MD10, 4 Medical Drive, National University of Singapore, Singapore 117594, Singapore; Singapore Eye Research Institute c/o Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore. Electronic address: antkaurc@nus.edu.sg.
authors.forename: Charanjit
authors.initials: C
authors.lastname: Kaur
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001813:Blood-Retinal Barrier; D015153:Blotting, Western; D002199:Capillary Permeability; D062507:Claudin-5 / Q000235:genetics* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure*; D019084:Fluorescent Antibody Technique, Indirect; D000860:Hypoxia / Q000473:pathology*; D008854:Microscopy, Electron; D062793:Occludin / Q000235:genetics* / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000254:growth & development*; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000648:ultrastructure; D012171:Retinal Vessels / Q000378:metabolism / Q000648:ultrastructure*; D062826:Zonula Occludens-1 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D062507:Claudin-5; C491510:Cldn5 protein, rat; D062793:Occludin; C568987:Ocln protein, rat; D011509:Proteoglycans; D012333:RNA, Messenger; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein
keywords: Blood retinal barrier; Developing retina; Endothelial cell specific molecule-1; Hypoxia; Tight junctions