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Biochemical alterations in the retinas of very low-density lipoprotein receptor knockout mice: an animal model of retinal angiomatous proliferation.
- Source :
-
Archives of ophthalmology (Chicago, Ill. : 1960) [Arch Ophthalmol] 2007 Jun; Vol. 125 (6), pp. 795-803. - Publication Year :
- 2007
-
Abstract
- 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.<br />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.<br />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.<br />Conclusion: An inflammatory process is involved in the development of neovascularization in the VLDLr knockout mouse retina.<br />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.
- Subjects :
- Animals
Blotting, Western
Electrophoretic Mobility Shift Assay
Eye Proteins metabolism
Glial Fibrillary Acidic Protein metabolism
Immunohistochemistry
Intercellular Adhesion Molecule-1 metabolism
Interleukin-18 metabolism
Mice
Mice, Knockout
Mitogen-Activated Protein Kinases metabolism
NF-kappa B metabolism
Nerve Growth Factors metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt metabolism
Retina pathology
Retinal Neovascularization pathology
Reverse Transcriptase Polymerase Chain Reaction
Serpins metabolism
Vascular Endothelial Growth Factor A metabolism
Disease Models, Animal
Receptors, LDL physiology
Retina metabolism
Retinal Neovascularization metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0003-9950
- Volume :
- 125
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Archives of ophthalmology (Chicago, Ill. : 1960)
- Publication Type :
- Academic Journal
- Accession number :
- 17562991
- Full Text :
- https://doi.org/10.1001/archopht.125.6.795