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 Müller 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.


CONCLUSIONS
An inflammatory process is involved in the development of neovascularization in the VLDLr knockout mouse retina.


CONCLUSIONS
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.
Li
Chao
C
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Dean A. McGee Eye Institute, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.
Huang
Zhong
Z
Kingsley
Ronald
R
Zhou
Xiaohong
X
Li
Feng
F
Parke
David W
DW
Cao
Wei
W
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D005136:Eye Proteins / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011973:Receptors, LDL / Q000502:physiology*; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D015861:Retinal Neovascularization / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; D018799:Intercellular Adhesion Molecule-1; D020382:Interleukin-18; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D009414:Nerve Growth Factors; D051057:Proto-Oncogene Proteins c-akt; D011973:Receptors, LDL; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C090509:Icam1 protein, mouse; C036053:VLDL receptor; C467480:vascular endothelial growth factor A, mouse