THE 67-KD LAMININ RECEPTOR IS PREFERENTIALLY EXPRESSED BY PROLIFERATING RETINAL-VESSELS IN A MURINE MODEL OF ISCHEMIC RETINOPATHY

Endothelial cell association with vascular basement membranes is compl ex and plays a critical role in regulation of cell adhesion and prolif eration. The interaction bem een the membrane-associated 67-kd recepto r (67LR) and the basement membrane protein laminin has been studied in several cell systems where it was shown to be crucial for adhesion an d 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 neovasculariza tion. 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, ther e was consistent preretinal neovascularization starting around P17, wh ich persisted until P21, after which the new vessels regressed. Immuno histochemistry was performed on these retinas using an antibody specif ic for 67LR, At P12, immunoreactivity for 67LR was absent in the retin a, but by P17 it was observed in preretinal proliferating vessels and also within the adjacent intraretinal vasculature, Intraretinal 67LR i mmunoreactivity diminished beyond P17 until by P21 immunoreactivity wa s almost completely absent, although it persisted in the preretinal va sculature. Control P17 mice (not exposed to hyperoxia) failed to demon strate any 67LR immunoreactivity in their retinas. Parallel in situ hy bridization studies demonstrated 67LR gene expression in the retinal g anglion 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 ische mic retinopathy. Results suggest that, although the 67LR gene is expre ssed at high levels in the retinal ganglion cells, the mature receptor protein is preferentially localized to the proliferating retinal vasc ulature and is almost completely absent from quiescent vessels. The di fferential expression of 67LR between proliferating and quiescent reti nal vessels suggests that this laminin receptor is an important and no vel target for future chemotherapeutic intervention during proliferati ve vasculopathies.