April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Cellular Mechanism and Treatment of Outer Blood-Retina Barrier Breakdown in Uveitis
Author Affiliations & Notes
  • H. Xu
    Medicine, Harold Hamm Oklahoma Diabetes Center,
    University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
    Ophthalmology, Xiangya Hospital, Central South University, Changsha, China
  • Y.-Z. Le
    Medicine, Cell Biology, Harold Hamm Oklahoma Diabetes Center,
    University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
    Dean A. McGee Eye Institute, Oklahoma City, Oklahoma
  • Footnotes
    Commercial Relationships  H. Xu, None; Y.-Z. Le, None.
  • Footnotes
    Support  NIH grants P20RR17703, P20RR024215, P30EY12190, ADA grants 1-06-RA-76, 1-10-BS-94, AHAF grant M2008-059, FFB grant BR-CMM-0808-0453-UOK, OCAST grant HR09-058
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 6380. doi:
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      H. Xu, Y.-Z. Le; Cellular Mechanism and Treatment of Outer Blood-Retina Barrier Breakdown in Uveitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6380.

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Abstract

Purpose: : Uveitis is responsible for approximately 10% cases of severe vision impairment in the United States. To determine the role of outer blood-retina barrier (BRB) breakdown in posterior uveitis and explore the therapeutic strategies for the disease, we investigated outer BRB-specific leakage and severity of exudative retinal detachment in mice with altered RPE barrier using a uveitis model.

Methods: : Mice with altered outer BRB were generated by disrupting vascular endothelial growth factor (VEGF), a regulator of BRB function, in the RPE. Uveitis in the conditional VEGF knockout (KO) mice was generated with an endotoxin-induced uveitis (EIU) model. The alteration of outer BRB was assessed by measuring tight-junction protein occludin in the RPE with Western blot and immunohistochemistry in the EIU-treated conditional VEGF KO mice. Outer BRB-specific breakdown in the EIU-treated conditional VEGF KO mice was examined by visualizing and measuring leaked macromolecules using our recently established fluorescent microscopic assay. The severity of exudative retinal detachment was examined and quantified with light microscopy.

Results: : While wild-type (WT) controls had severe outer BRB-specific leakage of macromolecules in the subretinal gap and a high level of exudative retinal detachment, the EIU-treated conditional VEGF KO mice demonstrated a significant reduction in the size of retinal detachments and the amount of outer BRB-specific leakage. These changes were associated with attenuation of EIU-induced occludin depletion in the conditional VEGF KO mice. Finally, injecting VEGF neutralizing antibody into the vitreous cavity of WT mice caused a significant reduction of EIU-induced outer BRB-specific leakage and exudative retinal detachment.

Conclusions: : Our study is the first to demonstrate the outer BRB-specific leakage in an EIU mouse model. Our results suggest that outer BRB breakdown contributed significantly to the severity of pathological changes in posterior uveitis and anti-VEGF approach may be useful to treat the disease.

Keywords: uveitis-clinical/animal model • retinal detachment • retinal pigment epithelium 
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