The
low-density lipoprotein receptor-related protein-1 (LRP-1) is a high-molecular weight receptor of the
LDL receptor gene family. Its ability to bind and internalize both
proteinases and
proteinase-inhibitor complexes from the extracellular space suggests that it has a major role in modulating uncontrolled
retinal cell proliferation. In order to test this assumption, we investigated the expression of LRP-1 and receptor-associated
ligands in a rat model of
oxygen-induced
retinal neovascularization. Wistar albino rats were placed into
incubators at birth and exposed to an atmosphere alternating between 50% and 10% of
oxygen every 24 h. After 14 days, the animals were allowed to recover in room air and sacrificed at postnatal day 20 (P20). The
protein expression of LRP-1 and
alpha2-macroglobulin (alpha2M) in the retina from unexposed and
hyperoxia-exposed rats was investigated by Western blot. The localization of LRP-1 after neovascularization was assessed by immunohistochemical staining. The activity of
metalloproteinases (
MMPs) was determined by zymography. Histological analysis was done to quantitate the neovascular response in these animals. Western blot analysis showed that LRP-1 was expressed, along with alpha2M, in the retina of rats with
oxygen-induced neovascularization at P20. By immunohistochemical analysis, positive staining for LRP-1 appeared in cells extending from the inner limiting membrane (ILM) to the outer limiting membrane (OLM). The cells of the retina that expressed LRP-1 were identified by immunofluorescence as Müller cells. Zymographic analysis demonstrated increased activity of MMP-2 and MMP-9 under neovascular conditions. This is the first demonstration of the involvement of LRP-1 in
retinal neovascularization. In retinas of rats with
oxygen-induced neovascularization, the expression of LRP-1 and alpha2M was increased along with an enhanced activity of
MMPs, suggesting that LRP-1 expression may play a role in modulating
retinal neovascularization by regulating proteolytic activity.