Suppression of Choroidal Neovascularization in Lectin-like Oxidized Low-Density Lipoprotein Receptor Type 1-Deficient Mice

PURPOSE. To elucidate the role of the scavenger receptor, lectinlike oxidized low-density lipoprotein receptor type 1 (LOX-1), in the formation of choroidal neovascularization (CNV). METHODS. CNV was induced by laser photocoagulation of the ocular fundus in mice. The expression of LOX-1 mRNA and protein after laser injury was determined by real-time RT-PCR and Western blot analysis. Gelatin zymography was used to measure the activity of matrix metalloproteinase (MMP)-2 and pro-MMP-9, and ELISA was used to determine monocyte chemoattractant protein (MCP)-1 and vascular endothelial growth factor (VEGF) levels. At 14 days after laser injury, the extent of CNV was evaluated by fluorescein angiography and lectin staining using confocal microscopy. RESULTS. In wild-type mice, the relative expression level of LOX-1 mRNA compared with the control increased significantly 6 hours after laser injury and peaked 12 hours after laser injury (P ϭ 0.011 and P ϭ 0.0006, respectively), and the expression of LOX-1 protein was also detected 1 and 3 days after laser injury. Increases in MMP-2, pro-MMP2, and pro-MMP-9 after laser injury were reduced in LOX-1-deficient mice compared with wild-type mice. At 3 days after laser injury, increases in MCP-1 and VEGF significantly decreased in LOX-1-deficient mice compared with wild-type mice (P ϭ 0.014 and P ϭ 0.001, respectively). Morphometric analyses revealed that the induction of CNV formation was significantly inhibited in LOX-1-deficient mice. CONCLUSIONS. These results suggest that LOX-1 plays an important role in the formation of CNV. This scavenging system might thus be a novel therapeutic target for CNV. (Invest Ophthalmol Vis Sci. 2009;50:3970 -3976) DOI:10.1167/iovs.07-1177 A ge-related macular degeneration (AMD) is the leading cause of legal blindness in persons older than 55 in developed countries. 1 Late AMD is subdivided into two forms, atrophic and (neovascular) exudative. The latter is associated with the most severe cases of visual loss caused by the growth of abnormal new vessels under the retinal pigment epithelium (RPE) from the choroid, leading to choroidal neovascularization (CNV). The pathogenesis of AMD is regarded as multifactorial, with age, genetic background, environmental risks, and systemic conditions playing important roles in its progression. 2-4 Although adhesion molecules, cytokines, and growth factors have been identified as contributing factors, the molecular mechanisms relating to AMD pathogenesis are not well understood. Recently, similarities have been suggested between the pathogenesis of AMD and atherosclerosis