title: The 67-kd laminin receptor is preferentially expressed by proliferating retinal vessels in a murine model of ischemic retinopathy.
abstract: Endothelial cell association with vascular basement membranes is complex and plays a critical role in regulation of cell adhesion and proliferation. The interaction between the membrane-associated 67-kd receptor (67LR) and the basement membrane protein laminin has been studied in several cell systems where it was shown to be crucial for adhesion and attachment during angiogenesis. As angiogenesis in the pathological setting of proliferative retinopathy is a major cause of blindness in the Western world we examined the expression of 67LR in a murine model of hyperoxia-induced retinopathy that exhibits retinal neovascularization. Mice exposed to hyperoxia for 5 days starting at postnatal day 7 (P7) and returned to room air (at P12) showed closure of the central retinal vasculature. In response to the ensuing retinal ischemia, there was consistent preretinal neovascularization starting around P17, which persisted until P21, after which the new vessels regressed. Immunohistochemistry was performed on these retinas using an antibody specific for 67LR. At P12, immunoreactivity for 67LR was absent in the retina, but by P17 it was observed in preretinal proliferating vessels and also within the adjacent intraretinal vasculature. Intraretinal 67LR immunoreactivity diminished beyond P17 until by P21 immunoreactivity was almost completely absent, although it persisted in the preretinal vasculature. Control P17 mice (not exposed to hyperoxia) failed to demonstrate any 67LR immunoreactivity in their retinas. Parallel in situ hybridization studies demonstrated 67LR gene expression in the retinal ganglion cells of control and hyperoxia-exposed mice. In addition, the neovascular intra- and preretinal vessels of hyperoxia-treated P17 and P21 mice labeled strongly for 67LR mRNA. This study has characterized 67LR immunolocalization and gene expression in a murine model of ischemic retinopathy. Results suggest that, although the 67LR gene is expressed at high levels in the retinal ganglion cells, the mature receptor protein is preferentially localized to the proliferating retinal vasculature and is almost completely absent from quiescent vessels. The differential expression of 67LR between proliferating and quiescent retinal vessels suggests that this laminin receptor is an important and novel target for future chemotherapeutic intervention during proliferative vasculopathies.
authors.affiliation: Department of Ophthalmology, The Queen's University of Belfast, United Kingdom. a.stitt@qub.ac.uk
authors.forename: A W
authors.initials: AW
authors.lastname: Stitt
authors.forename: D
authors.initials: D
authors.lastname: McKenna
authors.forename: D A
authors.initials: DA
authors.lastname: Simpson
authors.forename: T A
authors.initials: TA
authors.lastname: Gardiner
authors.forename: P
authors.initials: P
authors.lastname: Harriott
authors.forename: D B
authors.initials: DB
authors.lastname: Archer
authors.forename: J
authors.initials: J
authors.lastname: Nelson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005260:Female; D005451:Fluorescein Angiography; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D018496:Hyperoxia / Q000150:complications; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007231:Infant, Newborn; D007511:Ischemia / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism*; D015861:Retinal Neovascularization / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D017474:Receptors, Laminin; D016650:Fluorescein-5-isothiocyanate