Expression of LOX-1, an oxidized low-density lipoprotein receptor, in choroidal neovascularization.

Subfoveal choroidal neovascularization of various macular diseases is one of the causes of severe blindness, including age-related macular degeneration (AMD). Several environmental risk factors have been elucidated in the pathogenesis of AMD, including smoking, atherosclerosis, increased levels of plasma fibrinogen, and low levels of antioxidant vitamins. Recent observations support the hypothesis that antioxidant and/or vitamin treatment may delay progression of AMD and vision loss. However, the exact cause of AMD remains to be determined. Recently, Ikeda et al showed that increased plasma oxidized lowdensity lipoprotein (oxLDL) levels may be involved in the pathogenesis of AMD. Oxidized LDL has been implicated as having a major role in atherosclerosis, and many of the pathologic and biochemical features seen in choroidal neovascularization are analogous to those seen in advanced atherosclerosis, such as the infiltration of monocytes and macrophages and the overexpression of adhesion molecules, monocyte chemotactic proteins, growth factors, and cytokines within lesions. Lectinlike oxidized lowdensity lipoprotein receptor type 1 (LOX-1) is a recently identified oxLDL receptor that is abundantly expressed in vascular endothelial cells. Its messenger RNA has been shown to be expressed in atheromatous lesions, and LOX-1 up-regulation has been observed in several vascular lesions, including hypertensive remodeling lesions, diabetic vascular lesions, and macrophages. The observation of LOX-1 up-regulation in vascular lesions, the potential roles of oxLDL in the pathogenesis of AMD, and the possible similarity between the pathogenesis of atherosclerosis and that of AMD prompted us to examine LOX-1 expression in choroidal neovascularization. In addition, we sought to measure plasma cholesterol levels to investigate the relationship between LOX-1 expression and hyperlipidemia. We examined LOX-1 localization in 13 surgically excised neovascular membranes, including 10 from patients with AMD, 1 from a patient with idiopathic choroidal neovascularization, and 2 from patients with myopic choroidal neovascularization. The membranes were frozen in liquid nitrogen within 30 minutes of excision. Multiple 8-μm cryosections from each membrane were air-dried, fixed in acetone for 5 minutes, washed with phosphate-buffered saline, and blocked for 30 minutes with 2% bovine serum albumin in phosphatebuffered saline. They were then incubated with primary antibody and washed 3 times for 5 minutes with