[Molecular mechanism of choroidal neovascularization in age-related macular degeneration].
The exudative form of age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). Retinal pigment epithelial cells (RPE) secrete various angiogenesis-related factors, especially vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF). The imbalance between the VEGF and PEDF secreted by RPE is a key contributor to the development of CNV in AMD. The earliest clinical hallmark of AMD is the presence of drusen. Although drusen are an epidemiological risk factor for the development of CNV, the mechanism of how drusen induce the development of CNV remains unclear. Recent proteome analysis demonstrated that amyloid beta (Abeta) deposition was specific to drusen from eyes with AMD. We focused on Abeta and investigated the effect of Abeta on cultured human RPE cells as well as ocular findings in neprilysin gene-disrupted mice, which leads to an increased deposition of Abeta. Our study demonstrates that Abeta accumulation affects the balance between VEGF and PEDF in the RPE, and reproduces features characteristic of human AMD, such as RPE atrophy and basal deposit formation in neprilysin gene-disrupted mice.
Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan. takec.oph@tmd.ac.jp
Takeshi
T
Yoshida
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D020256:Choroidal Neovascularization / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism; D006801:Humans; D008268:Macular Degeneration / Q000378:metabolism*; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D015843:Serpins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
D016229:Amyloid beta-Peptides; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor