Biochemical Alterations in the Retinas of Very Low-Density Lipoprotein Receptor Knockout Mice An Animal Model of Retinal Angiomatous Proliferation

Objective To identify and characterize biochemical alterations in the retinas of very low-density lipoprotein receptor (VLDLr) knockout mice in an animal model of retinal angiomatous proliferation. Methods Immunohistochemical analysis, Western blot analysis, reverse transcriptase–polymerase chain reaction, and electrophoretic mobility shift assay were used to identify and characterize the altered gene and protein expression as well as signal cascades involved in the pathogenesis of neovascularization in the retinas of VLDLr mice. Results Expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor was significantly greater in the lesion area, and Muller cells around the lesion area were activated, as indicated by increased expression of glial fibrillary acidic protein. Expression of the proinflammatory cytokine IL-18 (interleukin 18) and the inflammation mediator intercellular adhesion molecule-1 was increased before significant intraretinal neovascularization. Furthermore, phosphorylation of Akt and mitogen-activated protein kinase and translocalization of nuclear factor kappa B were greater in VLDLr knockout mouse retinas. Conclusion An inflammatory process is involved in the development of neovascularization in the VLDLr knockout mouse retina. Clinical Relevance Understanding the molecular mechanisms underlying these biochemical alterations in the retinas of VLDLr knockout mice will provide a foundation for developing novel therapeutic approaches to retinal angiomatous proliferation.