May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Possible Involvement of Inflammatory Process in the Development of Neovascularization in the Retina of Very Low Density Lipoprotein Receptor (VLDLr) Deficient Mouse
Author Affiliations & Notes
  • Z. Huang
    Ophthalmology, Dean McGee Eye Institute, Oklahoma City, Oklahoma
  • C. Li
    Ophthalmology, Dean McGee Eye Institute, Oklahoma City, Oklahoma
  • R. Kingsley
    Ophthalmology, Dean McGee Eye Institute, Oklahoma City, Oklahoma
  • R. Kingsley
    Ophthalmology, Dean McGee Eye Institute, Oklahoma City, Oklahoma
  • D. W. Parke
    Ophthalmology, Dean McGee Eye Institute, Oklahoma City, Oklahoma
  • W. Cao
    Ophthalmology, Dean McGee Eye Institute, Oklahoma City, Oklahoma
  • Footnotes
    Commercial Relationships Z. Huang, None; C. Li, None; R. Kingsley, None; R. Kingsley, None; D.W. Parke, None; W. Cao, None.
  • Footnotes
    Support Foundation Fighting Blindness (FFB), and NIH grant P20 RR017703 from COBRE, and an unrestricted grant from RPB to the Dept. of Ophthal., OUHSC, and a NIH core grant EY12190, and OCAST Grant HR06-012.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3025. doi:
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      Z. Huang, C. Li, R. Kingsley, R. Kingsley, D. W. Parke, W. Cao; Possible Involvement of Inflammatory Process in the Development of Neovascularization in the Retina of Very Low Density Lipoprotein Receptor (VLDLr) Deficient Mouse. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3025.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: Age-related macular degeneration (AMD) is leading causes of blindness. Retinal angiomatous proliferation (RAP) was first described as deep-retinal vascular anomalous complex, then as occult retinal choroidal anastomosis. It is a form of AMD that is characterized by the neovascularization process starting in the retina rather than the choroids, and comprises 10-15% of the neovascular AMD cases. The etiology and the biochemical mechanisms responsible for RAP are still unknown. The very low density lipoprotein receptor (VLDLr) knockout mouse presents several morphological alterations in the retina similar to RAP in humans. In present study, we examined the biochemical alterations and the pathological process in the development of neovascularization in the retina of this mouse.

Methods:: Retinal morphology was evaluated by vascularization in histology. The leakage study was performed through the left ventricle with a 50 mg/ml fluorescein-dextran. Immunohistochemistry, western blot analysis, RT-PCR and electrophoreic mobility shift assay were used to characterize and identify the altered gene and protein as well as signal cascades involved in the pathogenesis of neovascularization in the retina of VLDLr mouse.

Results:: The mRNA and protein levels of angiogenic factors VEGF and bfgf were significantly greater in VLDLr knock out mouse than with that wild type mouse. The Müller cells around the lesion area were clearly activated as indicated by increased expression of GFAP. Interestingly, expression of the pro-inflammatory cytokine IL-18 and the inflammation mediator ICAM-1 were increased before significant intraretinal neovascularization. Furthermore, the phosphorylation of Akt and mapk, and the translocalization of NF-B were also greater in the VLDLr knockout mouse retinas.

Conclusions:: Chronic inflammatory processes may be initiated due to the accumulation of cell debris in the subretinal space to activate retinal Müller cells. This may cause an increase in the expression and the release of VEGF and bFGF from the Müller cells, which may stimulate the development of neovascularization in the VLDLr knockout mouse retina.

Keywords: age-related macular degeneration • retinal neovascularization • retinal degenerations: cell biology 
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